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What are the genetic changes related to atopic dermatitis ?
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The genetics of atopic dermatitis are not completely understood. Studies suggest that several genes can be involved in development of the condition. The strongest association is with the FLG gene, which is mutated in 20 to 30 percent of people with atopic dermatitis compared with 8 to 10 percent of the general population without atopic dermatitis. The FLG gene provides instructions for making a protein called profilaggrin, which is cut (cleaved) to produce multiple copies of the filaggrin protein. Filaggrin is involved in creating the structure of the outermost layer of skin, creating a strong barrier to keep in water and keep out foreign substances, including toxins, bacteria, and substances that can cause allergic reactions (allergens), such as pollen and dust. Further processing of the filaggrin protein produces other molecules that are part of the skin's "natural moisturizing factor," which helps maintain hydration of the outermost layer of skin. Mutations in the FLG gene lead to production of an abnormally short profilaggrin molecule that cannot be cleaved to produce filaggrin proteins. The resulting shortage of filaggrin can impair the barrier function of the skin. In addition, a lack of natural moisturizing factor allows excess water loss through the skin, which can lead to dry skin. Research shows that impairment of the skin's barrier function contributes to development of allergic disorders. An allergic reaction occurs when the body mistakenly recognizes a harmless substance, such as pollen, as a danger and stimulates an immune response to it. Research suggests that without a properly functioning barrier, allergens are able to get into the body through the skin. For unknown reasons, in susceptible individuals the body reacts as if the allergen is harmful and produces immune proteins called IgE antibodies specific to the allergen. Upon later encounters with the allergen, IgE antibodies recognize it, which stimulates an immune response, causing the symptoms of allergies, such as itchy, watery eyes or breathing difficulty. Although atopic dermatitis is not initially caused by an allergic reaction, flare-ups of the rashes can be triggered by allergens. The impaired barrier function caused by FLG gene mutations also contributes to the increased risk of asthma and other allergic disorders in people with atopic dermatitis. Mutations in many other genes, most of which have not been identified, are likely associated with development of atopic dermatitis. Researchers suspect these genes are involved in the skin's barrier function or in the function of the immune system. However, not everyone with a mutation in FLG or another associated gene develops atopic dermatitis; exposure to certain environmental factors also contributes to the development of the disorder. Studies suggest that these exposures trigger epigenetic changes to the DNA. Epigenetic changes modify DNA without changing the DNA sequence. They can affect gene activity and regulate the production of proteins, which may influence the development of allergies in susceptible individuals.
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Is atopic dermatitis inherited ?
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Allergic disorders tend to run in families; having a parent with atopic dermatitis, asthma, or hay fever raises the chances a person will develop atopic dermatitis. When associated with FLG gene mutations, atopic dermatitis follows an autosomal dominant inheritance pattern, which means one copy of the altered FLG gene in each cell is sufficient to increase the risk of the disorder. Individuals with two altered copies of the gene are more likely to develop the disorder and can have more severe signs and symptoms than individuals with a single altered copy. When associated with other genetic factors, the inheritance pattern is unclear. People with changes in one of the genes associated with atopic dermatitis, including FLG, inherit an increased risk of this condition, not the condition itself. Not all people with this condition have a mutation in an associated gene, and not all people with a variation in an associated gene will develop the disorder.
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What are the treatments for atopic dermatitis ?
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These resources address the diagnosis or management of atopic dermatitis: - American Academy of Dermatology: Atopic Dermatitis: Tips for Managing These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) 3-M syndrome ?
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3-M syndrome is a disorder that causes short stature (dwarfism), unusual facial features, and skeletal abnormalities. The name of this condition comes from the initials of three researchers who first identified it: Miller, McKusick, and Malvaux. Individuals with 3-M syndrome grow extremely slowly before birth, and this slow growth continues throughout childhood and adolescence. They have low birth weight and length and remain much smaller than others in their family, growing to an adult height of approximately 120 centimeters to 130 centimeters (4 feet to 4 feet 6 inches). Affected individuals have a normally sized head that looks disproportionately large in comparison with their body. The head may be unusually long and narrow in shape (dolichocephalic). In addition to short stature, people with 3-M syndrome have a triangle-shaped face with a broad, prominent forehead (frontal bossing) and a pointed chin; the middle of the face is less prominent (hypoplastic midface). They may have large ears, full eyebrows, an upturned nose with a fleshy tip, a long area between the nose and mouth (philtrum), a prominent mouth, and full lips. Affected individuals may have a short, broad neck and chest with prominent shoulder blades and square shoulders. They may have abnormal spinal curvature such as a rounded upper back that also curves to the side (kyphoscoliosis) or exaggerated curvature of the lower back (hyperlordosis). People with 3-M syndrome may also have unusual curving of the fingers (clinodactyly), short fifth (pinky) fingers, prominent heels, and loose joints. Other skeletal abnormalities, such as unusually slender long bones in the arms and legs, tall, narrow spinal bones (vertebrae), or slightly delayed bone age may be apparent in x-ray images. 3-M syndrome can also affect other body systems. Males with 3-M syndrome may produce reduced amounts of sex hormones (hypogonadism) and occasionally have the urethra opening on the underside of the penis (hypospadias). People with this condition may be at increased risk of developing bulges in blood vessel walls (aneurysms) in the brain. Intelligence is unaffected by 3-M syndrome, and life expectancy is generally normal. A variant of 3-M syndrome called Yakut short stature syndrome has been identified in an isolated population in Siberia. In addition to having most of the physical features characteristic of 3-M syndrome, people with this form of the disorder are often born with respiratory problems that can be life-threatening in infancy.
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How many people are affected by 3-M syndrome ?
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3-M syndrome is a rare disorder. About 50 individuals with this disorder have been identified worldwide.
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What are the genetic changes related to 3-M syndrome ?
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Mutations in the CUL7 gene cause 3-M syndrome. The CUL7 gene provides instructions for making a protein called cullin-7. This protein plays a role in the cell machinery that breaks down (degrades) unwanted proteins, called the ubiquitin-proteasome system. Cullin-7 helps to assemble a complex known as an E3 ubiquitin ligase. This complex tags damaged and excess proteins with molecules called ubiquitin. Ubiquitin serves as a signal to specialized cell structures known as proteasomes, which attach (bind) to the tagged proteins and degrade them. The ubiquitin-proteasome system acts as the cell's quality control system by disposing of damaged, misshapen, and excess proteins. This system also regulates the level of proteins involved in several critical cell activities such as the timing of cell division and growth. Mutations in the CUL7 gene that cause 3-M syndrome disrupt the ability of the cullin-7 protein to bring together the components of the E3 ubiquitin ligase complex, interfering with the process of tagging other proteins with ubiquitin (ubiquitination). It is not known how impaired ubiquitination results in the specific signs and symptoms of 3-M syndrome.
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Is 3-M syndrome inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for 3-M syndrome ?
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These resources address the diagnosis or management of 3-M syndrome: - Gene Review: Gene Review: 3-M Syndrome - Genetic Testing Registry: Three M syndrome 1 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) 5-alpha reductase deficiency ?
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5-alpha reductase deficiency is a condition that affects male sexual development before birth and during puberty. People with this condition are genetically male, with one X and one Y chromosome in each cell, and they have male gonads (testes). Their bodies, however, do not produce enough of a hormone called dihydrotestosterone (DHT). DHT has a critical role in male sexual development, and a shortage of this hormone disrupts the formation of the external sex organs before birth. Many people with 5-alpha reductase deficiency are born with external genitalia that appear female. In other cases, the external genitalia do not look clearly male or clearly female (sometimes called ambiguous genitalia). Still other affected infants have genitalia that appear predominantly male, often with an unusually small penis (micropenis) and the urethra opening on the underside of the penis (hypospadias). During puberty, people with this condition develop some secondary sex characteristics, such as increased muscle mass, deepening of the voice, development of pubic hair, and a growth spurt. The penis and scrotum (the sac of skin that holds the testes) grow larger. Unlike many men, people with 5-alpha reductase deficiency do not develop much facial or body hair. Most affected males are unable to father a child (infertile). Children with 5-alpha reductase deficiency are often raised as girls. About half of these individuals adopt a male gender role in adolescence or early adulthood.
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How many people are affected by 5-alpha reductase deficiency ?
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5-alpha reductase deficiency is a rare condition; the exact incidence is unknown. Large families with affected members have been found in several countries, including the Dominican Republic, Papua New Guinea, Turkey, and Egypt.
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What are the genetic changes related to 5-alpha reductase deficiency ?
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Mutations in the SRD5A2 gene cause 5-alpha reductase deficiency. The SRD5A2 gene provides instructions for making an enzyme called steroid 5-alpha reductase 2. This enzyme is involved in processing androgens, which are hormones that direct male sexual development. Specifically, the enzyme is responsible for a chemical reaction that converts the hormone testosterone to DHT. DHT is essential for the normal development of male sex characteristics before birth, particularly the formation of the external genitalia. Mutations in the SRD5A2 gene prevent steroid 5-alpha reductase 2 from effectively converting testosterone to DHT in the developing reproductive tissues. These hormonal factors underlie the changes in sexual development seen in infants with 5-alpha reductase deficiency. During puberty, the testes produce more testosterone. Researchers believe that people with 5-alpha reductase deficiency develop secondary male sex characteristics in response to higher levels of this hormone. Some affected people also retain a small amount of 5-alpha reductase 2 activity, which may produce DHT and contribute to the development of secondary sex characteristics during puberty.
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Is 5-alpha reductase deficiency inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the SRD5A2 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but do not show signs and symptoms of the condition. Although people who are genetically female (with two X chromosomes in each cell) may inherit mutations in both copies of the SRD5A2 gene, their sexual development is not affected. The development of female sex characteristics does not require DHT, so a lack of steroid 5-alpha reductase 2 activity does not cause physical changes in these individuals. Only people who have mutations in both copies of the SRD5A2 gene and are genetically male (with one X and one Y chromosome in each cell) have the characteristic signs of 5-alpha reductase deficiency.
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What are the treatments for 5-alpha reductase deficiency ?
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These resources address the diagnosis or management of 5-alpha reductase deficiency: - Genetic Testing Registry: 3-Oxo-5 alpha-steroid delta 4-dehydrogenase deficiency - MedlinePlus Encyclopedia: Ambiguous Genitalia - MedlinePlus Encyclopedia: Intersex These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) nonsyndromic paraganglioma ?
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Paraganglioma is a type of noncancerous (benign) tumor that occurs in structures called paraganglia. Paraganglia are groups of cells that are found near nerve cell bunches called ganglia. Paragangliomas are usually found in the head, neck, or torso. However, a type of paraganglioma known as pheochromocytoma develops in the adrenal glands. Adrenal glands are located on top of each kidney and produce hormones in response to stress. Most people with paraganglioma develop only one tumor in their lifetime. Some people develop a paraganglioma or pheochromocytoma as part of a hereditary syndrome that may affect other organs and tissues in the body. However, the tumors often are not associated with any syndromes, in which case the condition is called nonsyndromic paraganglioma or pheochromocytoma. Pheochromocytomas and some other paragangliomas are associated with ganglia of the sympathetic nervous system. The sympathetic nervous system controls the "fight-or-flight" response, a series of changes in the body due to hormones released in response to stress. Although most sympathetic paragangliomas are pheochromocytomas, some are found outside the adrenal glands, usually in the abdomen, and are called extra-adrenal paragangliomas. Most sympathetic paragangliomas, including pheochromocytomas, produce hormones called catecholamines, such as epinephrine (adrenaline) or norepinephrine. These excess catecholamines can cause signs and symptoms such as high blood pressure (hypertension), episodes of rapid heartbeat (palpitations), headaches, or sweating. Most paragangliomas are associated with ganglia of the parasympathetic nervous system, which controls involuntary body functions such as digestion and saliva formation. Parasympathetic paragangliomas, typically found in the head and neck, usually do not produce hormones. However, large tumors may cause signs and symptoms such as coughing, hearing loss in one ear, or difficulty swallowing. Although most paragangliomas and pheochromocytomas are noncancerous, some can become cancerous (malignant) and spread to other parts of the body (metastasize). Extra-adrenal paragangliomas become malignant more often than other types of paraganglioma or pheochromocytoma.
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How many people are affected by nonsyndromic paraganglioma ?
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It is estimated that the prevalence of pheochromocytoma is 1 in 500,000 people, and the prevalence of other paragangliomas is 1 in 1 million people. These statistics include syndromic and nonsyndromic paraganglioma and pheochromocytoma.
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What are the genetic changes related to nonsyndromic paraganglioma ?
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The VHL, RET, SDHB, and SDHD genes can be mutated in both syndromic and nonsyndromic forms of paraganglioma and pheochromocytoma. Mutations in at least three additional genes, TMEM127, SDHA, and KIF1B, have been identified in people with the nonsyndromic form of these conditions. Gene mutations increase the risk of developing paraganglioma or pheochromocytoma by affecting control of cell growth and division. Mutations in the VHL, SDHA, SDHB, and SDHD genes increase the risk of developing nonsyndromic paraganglioma or pheochromocytoma. The protein produced from the VHL gene helps break down other, unneeded proteins, including a protein called HIF that stimulates cell division and blood vessel formation under certain cellular conditions. The proteins produced from the SDHA, SHDB, and SDHD genes are each pieces (subunits) of an enzyme that is important for energy production in the cell. This enzyme also plays a role in the breakdown of the HIF protein. Mutations in the VHL, SDHA, SDHB, and SDHD genes stabilize the HIF protein, causing it to build up in cells. Excess HIF protein stimulates cells to divide and triggers the production of blood vessels when they are not needed. Rapid and uncontrolled cell division, along with the formation of new blood vessels, can lead to the development of tumors. Mutations in the RET gene have been found in nonsyndromic pheochromocytoma in addition to a pheochromocytoma-predisposing syndrome. The protein produced from the RET gene is involved in signaling within cells that can stimulate cell division or maturation. Mutations in the RET gene overactivate the protein's signaling function, which can trigger cell growth and division in the absence of signals from outside the cell. This unchecked cell division can lead to the formation of tumors in the adrenal glands. Mutations in the TMEM127 gene have been identified most commonly in people with nonsyndromic pheochromocytoma and are rarely seen in people with other paraganglioma. The TMEM127 protein normally controls a signaling pathway that induces cell growth and survival. Studies suggest that mutations in the TMEM127 gene lead to abnormal activation of cell growth, which may cause tumor formation. Mutations in the KIF1B gene have been reported in nonsyndromic pheochromocytoma. Studies suggest that these mutations impair the function of the KIF1B protein, which normally triggers cells to self-destruct in a process called apoptosis. When apoptosis is impaired, cells grow and divide too quickly or in an uncontrolled way, potentially leading to tumor formation. Many people with nonsyndromic paraganglioma or pheochromocytoma do not have a mutation in any of the genes associated with the conditions. It is likely that other, unidentified genes also predispose to development of paraganglioma or pheochromocytoma.
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Is nonsyndromic paraganglioma inherited ?
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Nonsyndromic paraganglioma can be inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of developing a paraganglioma or pheochromocytoma. People with mutations in the gene inherit an increased risk of this condition, not the condition itself. Not all people with this condition have a mutation in the gene, and not all people with a gene mutation will develop the disorder. Most cases of nonsyndromic paraganglioma and pheochromocytoma are considered sporadic, which means the tumors occur in people with no history of the disorder in their family.
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What are the treatments for nonsyndromic paraganglioma ?
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These resources address the diagnosis or management of nonsyndromic paraganglioma: - Genetic Testing Registry: Pheochromocytoma These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) core binding factor acute myeloid leukemia ?
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Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer of the blood-forming tissue (bone marrow) called acute myeloid leukemia. In normal bone marrow, early blood cells called hematopoietic stem cells develop into several types of blood cells: white blood cells (leukocytes) that protect the body from infection, red blood cells (erythrocytes) that carry oxygen, and platelets (thrombocytes) that are involved in blood clotting. In acute myeloid leukemia, the bone marrow makes large numbers of abnormal, immature white blood cells called myeloid blasts. Instead of developing into normal white blood cells, the myeloid blasts develop into cancerous leukemia cells. The large number of abnormal cells in the bone marrow interferes with the production of functional white blood cells, red blood cells, and platelets. People with CBF-AML have a shortage of all types of mature blood cells: a shortage of white blood cells (leukopenia) leads to increased susceptibility to infections, a low number of red blood cells (anemia) causes fatigue and weakness, and a reduction in the amount of platelets (thrombocytopenia) can result in easy bruising and abnormal bleeding. Other symptoms of CBF-AML may include fever and weight loss. While acute myeloid leukemia is generally a disease of older adults, CBF-AML often begins in young adulthood and can occur in childhood. Compared to other forms of acute myeloid leukemia, CBF-AML has a relatively good prognosis: about 90 percent of individuals with CBF-AML recover from their disease following treatment, compared with 25 to 40 percent of those with other forms of acute myeloid leukemia. However, the disease recurs in approximately half of them after successful treatment of the initial occurrence.
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How many people are affected by core binding factor acute myeloid leukemia ?
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Acute myeloid leukemia occurs in approximately 3.5 per 100,000 individuals each year. CBF-AML accounts for 12 to 15 percent of acute myeloid leukemia cases in adults.
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What are the genetic changes related to core binding factor acute myeloid leukemia ?
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CBF-AML is associated with chromosomal rearrangements between chromosomes 8 and 21 and within chromosome 16. The rearrangements involve the RUNX1, RUNX1T1, CBFB, and MYH11 genes. Two of these genes, RUNX1 and CBFB, provide instructions for making the two pieces of a protein complex known as core binding factor (CBF). CBF attaches to certain regions of DNA and turns on genes that help control the development of blood cells (hematopoiesis). In particular, it plays an important role in development of hematopoietic stem cells. Chromosomal rearrangements involving the RUNX1 or CBFB gene alter CBF, leading to leukemia. In CBF-AML, the RUNX1 gene is affected by a type of genetic rearrangement known as a translocation; in this type of change, pieces of DNA from two chromosomes break off and are interchanged. The most common translocation in this condition, called t(8;21), fuses a part of the RUNX1 gene on chromosome 21 with part of the RUNX1T1 gene (also known as ETO) on chromosome 8. The combination of these genes leads to production of the RUNX1-ETO fusion protein. This fusion protein is able to form CBF and attach to DNA, like the normal RUNX1 protein. However, because the function of the protein produced from the normal RUNX1T1 gene is to block gene activity, the abnormal CBF turns genes off instead of turning them on. Other genetic rearrangements associated with CBF-AML alter the CBFB gene. One such rearrangement, called an inversion, involves breakage of a chromosome in two places; the resulting piece of DNA is reversed and reinserted into the chromosome. The inversion involved in CBF-AML (written as inv(16)) leads to the fusion of two genes on chromosome 16, CBFB and MYH11. Less commonly, a translocation involving chromosome 16, written as t(16;16), leads to the fusion of the same two genes. The protein produced from these genetic rearrangements is called CBF-MYH11. The fusion protein can form CBF, but it is thought that the presence of the MYH11 portion of the fusion protein prevents CBF from binding to DNA, impairing its ability to control gene activity. Alternatively, the MYH11 portion may interact with other proteins that prevent CBF from controlling gene activity. The change in gene activity caused by alteration of CBF blocks the maturation (differentiation) of blood cells and leads to the production of abnormal myeloid blasts. However, a chromosomal rearrangement alone is usually not enough to cause leukemia; one or more additional genetic changes are needed for cancer to develop. The additional changes likely cause the immature cells to grow and divide uncontrollably, leading to the excess of myeloid blasts characteristic of CBF-AML.
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Is core binding factor acute myeloid leukemia inherited ?
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CBF-AML is not inherited but arises from genetic rearrangements in the body's cells that occur after conception.
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What are the treatments for core binding factor acute myeloid leukemia ?
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These resources address the diagnosis or management of core binding factor acute myeloid leukemia: - Fred Hutchinson Cancer Research Center - Genetic Testing Registry: Acute myeloid leukemia - National Cancer Institute: Acute Myeloid Leukemia Treatment - St. Jude Children's Research Hospital These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) eosinophil peroxidase deficiency ?
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Eosinophil peroxidase deficiency is a condition that affects certain white blood cells called eosinophils but causes no health problems in affected individuals. Eosinophils aid in the body's immune response. During a normal immune response, these cells are turned on (activated), and they travel to the area of injury or inflammation. The cells then release proteins and other compounds that have a toxic effect on severely damaged cells or invading organisms. One of these proteins is called eosinophil peroxidase. In eosinophil peroxidase deficiency, eosinophils have little or no eosinophil peroxidase. A lack of this protein does not seem to affect the eosinophils' ability to carry out an immune response. Because eosinophil peroxidase deficiency does not cause any health problems, this condition is often diagnosed when blood tests are done for other reasons or when a family member has been diagnosed with the condition.
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How many people are affected by eosinophil peroxidase deficiency ?
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Approximately 100 individuals with eosinophil peroxidase deficiency have been described in the scientific literature. Based on blood test data, varying estimates of the prevalence of the condition have been reported in specific populations. Eosinophil peroxidase deficiency is estimated to occur in 8.6 in 1,000 Yemenite Jews, in 3 in 1,000 North-African Jews, and in 1 in 1,000 Iraqi Jews. In northeastern Italy, the condition occurs in approximately 1 in 14,000 individuals; in Japan it occurs in 1 in 36,000 people; and in Luxembourg, eosinophil peroxidase deficiency is thought to occur in 1 in 100,000 people.
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What are the genetic changes related to eosinophil peroxidase deficiency ?
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Mutations in the EPX gene cause eosinophil peroxidase deficiency. The EPX gene provides instructions for making the eosinophil peroxidase protein. During an immune response, activated eosinophils release eosinophil peroxidase at the site of injury. This protein helps form molecules that are highly toxic to bacteria and parasites. These toxic molecules also play a role in regulating inflammation by fighting microbial invaders. EPX gene mutations reduce or prevent eosinophil peroxidase production or result in a protein that is unstable and nonfunctional. As a result, eosinophils have severely reduced amounts of eosinophil peroxidase or none at all. Other proteins within affected eosinophils are normal, and while the cells lacking eosinophil peroxidase are smaller and may have structural changes, the loss of eosinophil peroxidase does not appear to impair the function of eosinophils.
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Is eosinophil peroxidase deficiency inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for eosinophil peroxidase deficiency ?
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These resources address the diagnosis or management of eosinophil peroxidase deficiency: - Genetic Testing Registry: Eosinophil peroxidase deficiency - Tulane University Eosinophilic Disorder Center These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) alpha thalassemia ?
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Alpha thalassemia is a blood disorder that reduces the production of hemoglobin. Hemoglobin is the protein in red blood cells that carries oxygen to cells throughout the body. In people with the characteristic features of alpha thalassemia, a reduction in the amount of hemoglobin prevents enough oxygen from reaching the body's tissues. Affected individuals also have a shortage of red blood cells (anemia), which can cause pale skin, weakness, fatigue, and more serious complications. Two types of alpha thalassemia can cause health problems. The more severe type is known as hemoglobin Bart hydrops fetalis syndrome or Hb Bart syndrome. The milder form is called HbH disease. Hb Bart syndrome is characterized by hydrops fetalis, a condition in which excess fluid builds up in the body before birth. Additional signs and symptoms can include severe anemia, an enlarged liver and spleen (hepatosplenomegaly), heart defects, and abnormalities of the urinary system or genitalia. As a result of these serious health problems, most babies with this condition are stillborn or die soon after birth. Hb Bart syndrome can also cause serious complications for women during pregnancy, including dangerously high blood pressure with swelling (preeclampsia), premature delivery, and abnormal bleeding. HbH disease causes mild to moderate anemia, hepatosplenomegaly, and yellowing of the eyes and skin (jaundice). Some affected individuals also have bone changes such as overgrowth of the upper jaw and an unusually prominent forehead. The features of HbH disease usually appear in early childhood, and affected individuals typically live into adulthood.
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How many people are affected by alpha thalassemia ?
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Alpha thalassemia is a fairly common blood disorder worldwide. Thousands of infants with Hb Bart syndrome and HbH disease are born each year, particularly in Southeast Asia. Alpha thalassemia also occurs frequently in people from Mediterranean countries, North Africa, the Middle East, India, and Central Asia.
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What are the genetic changes related to alpha thalassemia ?
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Alpha thalassemia typically results from deletions involving the HBA1 and HBA2 genes. Both of these genes provide instructions for making a protein called alpha-globin, which is a component (subunit) of hemoglobin. People have two copies of the HBA1 gene and two copies of the HBA2 gene in each cell. Each copy is called an allele. For each gene, one allele is inherited from a person's father, and the other is inherited from a person's mother. As a result, there are four alleles that produce alpha-globin. The different types of alpha thalassemia result from the loss of some or all of these alleles. Hb Bart syndrome, the most severe form of alpha thalassemia, results from the loss of all four alpha-globin alleles. HbH disease is caused by a loss of three of the four alpha-globin alleles. In these two conditions, a shortage of alpha-globin prevents cells from making normal hemoglobin. Instead, cells produce abnormal forms of hemoglobin called hemoglobin Bart (Hb Bart) or hemoglobin H (HbH). These abnormal hemoglobin molecules cannot effectively carry oxygen to the body's tissues. The substitution of Hb Bart or HbH for normal hemoglobin causes anemia and the other serious health problems associated with alpha thalassemia. Two additional variants of alpha thalassemia are related to a reduced amount of alpha-globin. Because cells still produce some normal hemoglobin, these variants tend to cause few or no health problems. A loss of two of the four alpha-globin alleles results in alpha thalassemia trait. People with alpha thalassemia trait may have unusually small, pale red blood cells and mild anemia. A loss of one alpha-globin allele is found in alpha thalassemia silent carriers. These individuals typically have no thalassemia-related signs or symptoms.
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Is alpha thalassemia inherited ?
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The inheritance of alpha thalassemia is complex. Each person inherits two alpha-globin alleles from each parent. If both parents are missing at least one alpha-globin allele, their children are at risk of having Hb Bart syndrome, HbH disease, or alpha thalassemia trait. The precise risk depends on how many alleles are missing and which combination of the HBA1 and HBA2 genes is affected.
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What are the treatments for alpha thalassemia ?
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These resources address the diagnosis or management of alpha thalassemia: - Gene Review: Gene Review: Alpha-Thalassemia - Genetic Testing Registry: alpha Thalassemia - MedlinePlus Encyclopedia: Thalassemia - University of California, San Francisco Fetal Treatment Center: Stem Cell Treatments These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) multiple lentigines syndrome ?
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Multiple lentigines syndrome (formerly called LEOPARD syndrome) is a condition that affects many areas of the body. The characteristic features associated with the condition include brown skin spots called lentigines that are similar to freckles, abnormalities in the electrical signals that control the heartbeat, widely spaced eyes (ocular hypertelorism), a narrowing of the artery from the heart to the lungs (pulmonary stenosis), abnormalities of the genitalia, short stature, and hearing loss. These features vary, however, even among affected individuals in the same family. Not all individuals affected with multiple lentigines syndrome have all the characteristic features of this condition. The lentigines seen in multiple lentigines syndrome typically first appear in mid-childhood, mostly on the face, neck, and upper body. Affected individuals may have thousands of brown skin spots by the time they reach puberty. Unlike freckles, the appearance of lentigines has nothing to do with sun exposure. In addition to lentigines, people with this condition may have lighter brown skin spots called caf-au-lait spots. Caf-au-lait spots tend to develop before the lentigines, appearing within the first year of life in most affected people. Abnormal electrical signaling in the heart can be a sign of other heart problems. Of the people with multiple lentigines syndrome who have heart problems, about 80 percent have hypertrophic cardiomyopathy, which is a thickening of the heart muscle that forces the heart to work harder to pump blood. The hypertrophic cardiomyopathy in affected individuals most often affects the lower left chamber of the heart (the left ventricle). Up to 20 percent of people with multiple lentigines syndrome who have heart problems have pulmonary stenosis. People with multiple lentigines syndrome can have a distinctive facial appearance. In addition to ocular hypertelorism, affected individuals may have droopy eyelids (ptosis), thick lips, and low-set ears. Abnormalities of the genitalia occur most often in males with multiple lentigines syndrome. The most common abnormality in affected males is undescended testes (cryptorchidism). Other males may have a urethra that opens on the underside of the penis (hypospadias). Males with multiple lentigines syndrome may have a reduced ability to have biological children (decreased fertility). Females with multiple lentigines syndrome may have poorly developed ovaries and delayed puberty. At birth, people with multiple lentigines syndrome are typically of normal weight and height, but in some, growth slows over time. This slow growth results in short stature in 50 to 75 percent of people with multiple lentigines syndrome. Approximately 20 percent of individuals with multiple lentigines syndrome develop hearing loss. This hearing loss is caused by abnormalities in the inner ear (sensorineural deafness) and can be present from birth or develop later in life. Other signs and symptoms of multiple lentigines syndrome include learning disorders, mild developmental delay, a sunken or protruding chest, and extra folds of skin on the back of the neck. Many of the signs and symptoms of multiple lentigines syndrome also occur in a similar disorder called Noonan syndrome. It can be difficult to tell the two disorders apart in early childhood. However, the features of the two disorders differ later in life.
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How many people are affected by multiple lentigines syndrome ?
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Multiple lentigines syndrome is thought to be a rare condition; approximately 200 cases have been reported worldwide.
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What are the genetic changes related to multiple lentigines syndrome ?
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Mutations in the PTPN11, RAF1, or BRAF genes cause multiple lentigines syndrome. Approximately 90 percent of individuals with multiple lentigines syndrome have mutations in the PTPN11 gene. RAF1 and BRAF gene mutations are responsible for a total of about 10 percent of cases. A small proportion of people with multiple lentigines syndrome do not have an identified mutation in any of these three genes. In these individuals, the cause of the condition is unknown. The PTPN11, RAF1, and BRAF genes all provide instructions for making proteins that are involved in important signaling pathways needed for the proper formation of several types of tissue during development. These proteins also play roles in the regulation of cell division, cell movement (migration), and cell differentiation (the process by which cells mature to carry out specific functions). Mutations in the PTPN11, RAF1, or BRAF genes lead to the production of a protein that functions abnormally. This abnormal functioning impairs the protein's ability to respond to cell signals. A disruption in the regulation of systems that control cell growth and division leads to the characteristic features of multiple lentigines syndrome.
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Is multiple lentigines syndrome inherited ?
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This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
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What are the treatments for multiple lentigines syndrome ?
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These resources address the diagnosis or management of multiple lentigines syndrome: - Cincinnati Children's Hospital: Cardiomyopathies - Gene Review: Gene Review: Noonan Syndrome with Multiple Lentigines - Genetic Testing Registry: LEOPARD syndrome 1 - Genetic Testing Registry: LEOPARD syndrome 2 - Genetic Testing Registry: LEOPARD syndrome 3 - Genetic Testing Registry: Noonan syndrome with multiple lentigines - MedlinePlus Encyclopedia: Hypertrophic Cardiomyopathy These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) achondrogenesis ?
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Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of serious health problems, infants with achondrogenesis usually die before birth, are stillborn, or die soon after birth from respiratory failure. However, some infants have lived for a short time with intensive medical support. Researchers have described at least three forms of achondrogenesis, designated as type 1A, type 1B, and type 2. The types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. However, types 1A and 1B are often hard to tell apart without genetic testing. Achondrogenesis type 1A, which is also called the Houston-Harris type, is the least well understood of the three forms. Affected infants have extremely short limbs, a narrow chest, short ribs that fracture easily, and a lack of normal bone formation (ossification) in the skull, spine, and pelvis. Achondrogenesis type 1B, also known as the Parenti-Fraccaro type, is characterized by extremely short limbs, a narrow chest, and a prominent, rounded abdomen. The fingers and toes are short and the feet may turn inward and upward (clubfeet). Affected infants frequently have a soft out-pouching around the belly-button (an umbilical hernia) or near the groin (an inguinal hernia). Infants with achondrogenesis type 2, which is sometimes called the Langer-Saldino type, have short arms and legs, a narrow chest with short ribs, and underdeveloped lungs. This condition is also associated with a lack of ossification in the spine and pelvis. Distinctive facial features include a prominent forehead, a small chin, and, in some cases, an opening in the roof of the mouth (a cleft palate). The abdomen is enlarged, and affected infants often have a condition called hydrops fetalis, in which excess fluid builds up in the body before birth.
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How many people are affected by achondrogenesis ?
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Achondrogenesis types 1A and 1B are rare genetic disorders; their incidence is unknown. Combined, achondrogenesis type 2 and hypochondrogenesis (a similar skeletal disorder) occur in 1 in 40,000 to 60,000 newborns.
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What are the genetic changes related to achondrogenesis ?
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Mutations in the TRIP11, SLC26A2, and COL2A1 genes cause achondrogenesis type 1A, type 1B, and type 2, respectively. The genetic cause of achondrogenesis type 1A was unknown until recently, when researchers discovered that the condition can result from mutations in the TRIP11 gene. This gene provides instructions for making a protein called GMAP-210. This protein plays a critical role in the Golgi apparatus, a cell structure in which newly produced proteins are modified so they can carry out their functions. Mutations in the TRIP11 gene prevent the production of functional GMAP-210, which alters the structure and function of the Golgi apparatus. Researchers suspect that cells called chondrocytes in the developing skeleton may be most sensitive to these changes. Chondrocytes give rise to cartilage, a tough, flexible tissue that makes up much of the skeleton during early development. Most cartilage is later converted to bone, except for the cartilage that continues to cover and protect the ends of bones and is present in the nose and external ears. Malfunction of the Golgi apparatus in chondrocytes likely underlies the problems with bone formation in achondrogenesis type 1A. Achondrogenesis type 1B is the most severe of a spectrum of skeletal disorders caused by mutations in the SLC26A2 gene. This gene provides instructions for making a protein that is essential for the normal development of cartilage and for its conversion to bone. Mutations in the SLC26A2 gene cause the skeletal problems characteristic of achondrogenesis type 1B by disrupting the structure of developing cartilage, which prevents bones from forming properly. Achondrogenesis type 2 is one of several skeletal disorders that result from mutations in the COL2A1 gene. This gene provides instructions for making a protein that forms type II collagen. This type of collagen is found mostly in cartilage and in the clear gel that fills the eyeball (the vitreous). It is essential for the normal development of bones and other connective tissues that form the body's supportive framework. Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules, which prevents bones and other connective tissues from developing properly.
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Is achondrogenesis inherited ?
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Achondrogenesis type 1A and type 1B both have an autosomal recessive pattern of inheritance, which means both copies of the TRIP11 or SLC26A2 gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene but do not show signs and symptoms of the condition. Achondrogenesis type 2 is considered an autosomal dominant disorder because one copy of the altered gene in each cell is sufficient to cause the condition. It is almost always caused by new mutations in the COL2A1 gene and typically occurs in people with no history of the disorder in their family.
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What are the treatments for achondrogenesis ?
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These resources address the diagnosis or management of achondrogenesis: - Gene Review: Gene Review: Achondrogenesis Type 1B - Genetic Testing Registry: Achondrogenesis type 2 - Genetic Testing Registry: Achondrogenesis, type IA - Genetic Testing Registry: Achondrogenesis, type IB - MedlinePlus Encyclopedia: Achondrogenesis These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) breast cancer ?
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Breast cancer is a disease in which certain cells in the breast become abnormal and multiply uncontrollably to form a tumor. Although breast cancer is much more common in women, this form of cancer can also develop in men. In both women and men, the most common form of breast cancer begins in cells lining the milk ducts (ductal cancer). In women, cancer can also develop in the glands that produce milk (lobular cancer). Most men have little or no lobular tissue, so lobular cancer in men is very rare. In its early stages, breast cancer usually does not cause pain and may exhibit no noticeable symptoms. As the cancer progresses, signs and symptoms can include a lump or thickening in or near the breast; a change in the size or shape of the breast; nipple discharge, tenderness, or retraction (turning inward); and skin irritation, dimpling, or scaliness. However, these changes can occur as part of many different conditions. Having one or more of these symptoms does not mean that a person definitely has breast cancer. In some cases, cancerous tumors can invade surrounding tissue and spread to other parts of the body. If breast cancer spreads, cancerous cells most often appear in the bones, liver, lungs, or brain. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. A small percentage of all breast cancers cluster in families. These cancers are described as hereditary and are associated with inherited gene mutations. Hereditary breast cancers tend to develop earlier in life than noninherited (sporadic) cases, and new (primary) tumors are more likely to develop in both breasts.
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How many people are affected by breast cancer ?
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Breast cancer is the second most commonly diagnosed cancer in women. (Only skin cancer is more common.) About one in eight women in the United States will develop invasive breast cancer in her lifetime. Researchers estimate that more than 230,000 new cases of invasive breast cancer will be diagnosed in U.S. women in 2015. Male breast cancer represents less than 1 percent of all breast cancer diagnoses. Scientists estimate that about 2,300 new cases of breast cancer will be diagnosed in men in 2015. Particular gene mutations associated with breast cancer are more common among certain geographic or ethnic groups, such as people of Ashkenazi (central or eastern European) Jewish heritage and people of Norwegian, Icelandic, or Dutch ancestry.
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What are the genetic changes related to breast cancer ?
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Cancers occur when a buildup of mutations in critical genesthose that control cell growth and division or repair damaged DNAallow cells to grow and divide uncontrollably to form a tumor. In most cases of breast cancer, these genetic changes are acquired during a person's lifetime and are present only in certain cells in the breast. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in breast cancer cells. Less commonly, gene mutations present in essentially all of the body's cells increase the risk of developing breast cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop breast cancer. Some breast cancers that cluster in families are associated with inherited mutations in particular genes, such as BRCA1 or BRCA2. These genes are described as "high penetrance" because they are associated with a high risk of developing breast cancer, ovarian cancer, and several other types of cancer in women who have mutations. Men with mutations in these genes also have an increased risk of developing several forms of cancer, including breast cancer. The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. They are described as tumor suppressors because they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair DNA repair, allowing potentially damaging mutations to persist in DNA. As these defects accumulate, they can trigger cells to grow and divide without control or order to form a tumor. A significantly increased risk of breast cancer is also a feature of several rare genetic syndromes. These include Cowden syndrome, which is most often caused by mutations in the PTEN gene; hereditary diffuse gastric cancer, which results from mutations in the CDH1 gene; Li-Fraumeni syndrome, which is usually caused by mutations in the TP53 gene; and Peutz-Jeghers syndrome, which typically results from mutations in the STK11 gene. The proteins produced from these genes act as tumor suppressors. Mutations in any of these genes can allow cells to grow and divide unchecked, leading to the development of a cancerous tumor. Like BRCA1 and BRCA2, these genes are considered "high penetrance" because mutations greatly increase a person's chance of developing cancer. In addition to breast cancer, mutations in these genes increase the risk of several other types of cancer over a person's lifetime. Some of the conditions also include other signs and symptoms, such as the growth of noncancerous (benign) tumors. Mutations in dozens of other genes have been studied as possible risk factors for breast cancer. These genes are described as "low penetrance" or "moderate penetrance" because changes in each of these genes appear to make only a small or moderate contribution to overall breast cancer risk. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1 or BRCA2 genes. Others act through different pathways. Researchers suspect that the combined influence of variations in these genes may significantly impact a person's risk of developing breast cancer. In many families, the genetic changes associated with hereditary breast cancer are unknown. Identifying additional genetic risk factors for breast cancer is an active area of medical research. In addition to genetic changes, researchers have identified many personal and environmental factors that contribute to a person's risk of developing breast cancer. These factors include gender, age, ethnic background, a history of previous breast cancer, certain changes in breast tissue, and hormonal and reproductive factors. A history of breast cancer in closely related family members is also an important risk factor, particularly if the cancer occurred in early adulthood.
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Is breast cancer inherited ?
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Most cases of breast cancer are not caused by inherited genetic factors. These cancers are associated with somatic mutations in breast cells that are acquired during a person's lifetime, and they do not cluster in families. In hereditary breast cancer, the way that cancer risk is inherited depends on the gene involved. For example, mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. Although breast cancer is more common in women than in men, the mutated gene can be inherited from either the mother or the father. In the other syndromes discussed above, the gene mutations that increase cancer risk also have an autosomal dominant pattern of inheritance. It is important to note that people inherit an increased likelihood of developing cancer, not the disease itself. Not all people who inherit mutations in these genes will ultimately develop cancer. In many cases of breast cancer that clusters in families, the genetic basis for the disease and the mechanism of inheritance are unclear.
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What are the treatments for breast cancer ?
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These resources address the diagnosis or management of breast cancer: - Gene Review: Gene Review: BRCA1 and BRCA2 Hereditary Breast/Ovarian Cancer - Gene Review: Gene Review: Hereditary Diffuse Gastric Cancer - Gene Review: Gene Review: Li-Fraumeni Syndrome - Gene Review: Gene Review: PTEN Hamartoma Tumor Syndrome (PHTS) - Gene Review: Gene Review: Peutz-Jeghers Syndrome - Genetic Testing Registry: Familial cancer of breast - Genomics Education Programme (UK): Hereditary Breast and Ovarian Cancer - National Cancer Institute: Breast Cancer Risk Assessment Tool - National Cancer Institute: Genetic Testing for BRCA1 and BRCA2: It's Your Choice - National Cancer Institute: Genetic Testing for Hereditary Cancer Syndromes These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) chorea-acanthocytosis ?
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Chorea-acanthocytosis is primarily a neurological disorder that affects movement in many parts of the body. Chorea refers to the involuntary jerking movements made by people with this disorder. People with this condition also have abnormal star-shaped red blood cells (acanthocytosis). This condition is one of a group of conditions called neuroacanthocytoses that involve neurological problems and abnormal red blood cells. In addition to chorea, another common feature of chorea-acanthocytosis is involuntary tensing of various muscles (dystonia), such as those in the limbs, face, mouth, tongue, and throat. These muscle twitches can cause vocal tics (such as grunting), involuntary belching, and limb spasms. Eating can also be impaired as tongue and throat twitches can interfere with chewing and swallowing food. People with chorea-acanthocytosis may uncontrollably bite their tongue, lips, and inside of the mouth. Nearly half of all people with chorea-acanthocytosis have seizures. Individuals with chorea-acanthocytosis may develop difficulty processing, learning, and remembering information (cognitive impairment). They may have reduced sensation and weakness in their arms and legs (peripheral neuropathy) and muscle weakness (myopathy). Impaired muscle and nerve functioning commonly cause speech difficulties in individuals with this condition, and can lead to an inability to speak. Behavioral changes are a common feature of chorea-acanthocytosis and may be the first sign of this condition. These behavioral changes may include changes in personality, obsessive-compulsive disorder (OCD), lack of self-restraint, and the inability to take care of oneself. The signs and symptoms of chorea-acanthocytosis usually begin in early to mid-adulthood. The movement problems of this condition worsen with age. Loss of cells (atrophy) in certain brain regions is the major cause of the neurological problems seen in people with chorea-acanthocytosis.
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How many people are affected by chorea-acanthocytosis ?
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It is estimated that 500 to 1,000 people worldwide have chorea-acanthocytosis.
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What are the genetic changes related to chorea-acanthocytosis ?
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Mutations in the VPS13A gene cause chorea-acanthocytosis. The VPS13A gene provides instructions for producing a protein called chorein; the function of this protein in the body is unknown. Some researchers believe that chorein plays a role in the movement of proteins within cells. Most VPS13A gene mutations lead to the production of an abnormally small, nonfunctional version of chorein. The VPS13A gene is active (expressed) throughout the body; it is unclear why mutations in this gene affect only the brain and red blood cells.
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Is chorea-acanthocytosis inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for chorea-acanthocytosis ?
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These resources address the diagnosis or management of chorea-acanthocytosis: - Gene Review: Gene Review: Chorea-Acanthocytosis - Genetic Testing Registry: Choreoacanthocytosis These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) spastic paraplegia type 3A ?
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Spastic paraplegia type 3A is one of a group of genetic disorders known as hereditary spastic paraplegias. These disorders are characterized by muscle stiffness (spasticity) and weakness in the lower limbs (paraplegia). Hereditary spastic paraplegias are often divided into two types: pure and complex. The pure types involve only the lower limbs, while the complex types also involve other areas of the body; additional features can include changes in vision, changes in intellectual functioning, difficulty walking, and disturbances in nerve function (neuropathy). Spastic paraplegia type 3A is usually a pure hereditary spastic paraplegia, although a few complex cases have been reported. In addition to spasticity and weakness, which typically affect both legs equally, people with spastic paraplegia type 3A can also experience progressive muscle wasting (amyotrophy) in the lower limbs, reduced bladder control, an abnormal curvature of the spine (scoliosis), loss of sensation in the feet (peripheral neuropathy), or high arches of the feet (pes cavus). The signs and symptoms of spastic paraplegia type 3A usually appear before the age of 10; the average age of onset is 4 years. In some affected individuals the condition slowly worsens over time, sometimes leading to a need for walking support.
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How many people are affected by spastic paraplegia type 3A ?
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Spastic paraplegia type 3A belongs to a subgroup of hereditary spastic paraplegias known as autosomal dominant hereditary spastic paraplegia, which has an estimated prevalence of 2 to 9 per 100,000 individuals. Spastic paraplegia type 3A accounts for 10 to 15 percent of all autosomal dominant hereditary spastic paraplegia cases.
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What are the genetic changes related to spastic paraplegia type 3A ?
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Mutations in the ATL1 gene cause spastic paraplegia type 3A. The ATL1 gene provides instructions for producing a protein called atlastin-1. Atlastin-1 is produced primarily in the brain and spinal cord (central nervous system), particularly in nerve cells (neurons) that extend down the spinal cord (corticospinal tracts). These neurons send electrical signals that lead to voluntary muscle movement. Atlastin-1 is involved in the growth of specialized extensions of neurons, called axons, which transmit nerve impulses that signal muscle movement. The protein also likely plays a role in the normal functioning of multiple structures within neurons and in distributing materials within these cells. ATL1 gene mutations likely lead to a shortage of normal atlastin-1 protein, which impairs the functioning of neurons, including the distribution of materials within these cells. This lack of functional atlastin-1 protein may also restrict the growth of axons. These problems can lead to the abnormal functioning or death of the long neurons of the corticospinal tracts. As a result, the neurons are unable to transmit nerve impulses, particularly to other neurons and muscles in the lower extremities. This impaired nerve function leads to the signs and symptoms of spastic paraplegia type 3A.
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Is spastic paraplegia type 3A inherited ?
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Spastic paraplegia type 3A is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In approximately 95 percent of cases, an affected person inherits the mutation from one affected parent.
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What are the treatments for spastic paraplegia type 3A ?
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These resources address the diagnosis or management of spastic paraplegia type 3A: - Gene Review: Gene Review: Hereditary Spastic Paraplegia Overview - Gene Review: Gene Review: Spastic Paraplegia 3A - Genetic Testing Registry: Spastic paraplegia 3 - Spastic Paraplegia Foundation, Inc.: Treatments and Therapies These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) gnathodiaphyseal dysplasia ?
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Gnathodiaphyseal dysplasia is a disorder that affects the bones. People with this condition have reduced bone mineral density (osteopenia), which causes the bones to be unusually fragile. As a result, affected individuals typically experience multiple bone fractures in childhood, often from mild trauma or with no apparent cause. While most bone tissue is less dense than normal in gnathodiaphyseal dysplasia, the outer layer (cortex) of the shafts of the long bones in the arms and legs is abnormally hard and thick (diaphyseal sclerosis). Bowing of the long bones also occurs in this disorder. Jaw problems are common in gnathodiaphyseal dysplasia; the prefix "gnatho-" in the condition name refers to the jaw. Affected individuals may develop bone infections (osteomyelitis) in the jaw, which can lead to pain, swelling, discharge of pus from the gums, loose teeth, and slow healing after teeth are lost or extracted. Areas of the jawbone may lose the protective coverage of the gums, which can result in deterioration of the exposed bone (osteonecrosis of the jaw). Also, normal bone in areas of the jaw may be replaced by fibrous tissue and a hard material called cementum, which normally surrounds the roots of teeth and anchors them in the jaw. These areas of abnormal bone, called cementoosseous lesions, may be present at birth or develop later in life. When gnathodiaphyseal dysplasia was first described, it was thought to be a variation of another bone disorder called osteogenesis imperfecta, which is also characterized by frequent bone fractures. However, gnathodiaphyseal dysplasia is now generally considered to be a separate condition. Unlike in osteogenesis imperfecta, the fractures in gnathodiaphyseal dysplasia heal normally without causing deformity or loss of height.
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How many people are affected by gnathodiaphyseal dysplasia ?
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The prevalence of gnathodiaphyseal dysplasia is unknown, but it is thought to be a rare disorder. A few affected individuals and families have been described in the medical literature.
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What are the genetic changes related to gnathodiaphyseal dysplasia ?
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Gnathodiaphyseal dysplasia is caused by mutations in the ANO5 gene, which provides instructions for making a protein called anoctamin-5. While the specific function of this protein is not well understood, it belongs to a family of proteins, called anoctamins, that act as chloride channels. Studies suggest that most anoctamin channels are turned on (activated) in the presence of positively charged calcium atoms (calcium ions); these channels are known as calcium-activated chloride channels. The mechanism for this calcium activation is unclear. The ANO5 gene mutations that have been identified in people with gnathodiaphyseal dysplasia change single protein building blocks (amino acids) in the anoctamin-5 protein. It is unclear how these protein changes lead to the fragile bones, jaw problems, and other skeletal abnormalities that occur in gnathodiaphyseal dysplasia. Researchers suggest that the mutations may affect the way cells process calcium, an important mineral in bone development and growth.
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Is gnathodiaphyseal dysplasia inherited ?
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This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family.
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What are the treatments for gnathodiaphyseal dysplasia ?
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These resources address the diagnosis or management of gnathodiaphyseal dysplasia: - Cleveland Clinic: Osteomyelitis - MedlinePlus Encyclopedia: Bone Mineral Density Testing These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) autosomal recessive axonal neuropathy with neuromyotonia ?
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Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Axonal neuropathy, a characteristic feature of this condition, is caused by damage to a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. In people with autosomal recessive axonal neuropathy with neuromyotonia, the damage primarily causes progressive weakness and wasting (atrophy) of muscles in the feet, legs, and hands. Muscle weakness may be especially apparent during exercise (exercise intolerance) and can lead to an unusual walking style (gait), frequent falls, and joint deformities (contractures) in the hands and feet. In some affected individuals, axonal neuropathy also causes decreased sensitivity to touch, heat, or cold, particularly in the lower arms or legs. Another feature of this condition is neuromyotonia (also known as Isaac syndrome). Neuromyotonia results from overactivation (hyperexcitability) of peripheral nerves, which leads to delayed relaxation of muscles after voluntary tensing (contraction), muscle cramps, and involuntary rippling movement of the muscles (myokymia).
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How many people are affected by autosomal recessive axonal neuropathy with neuromyotonia ?
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Autosomal recessive axonal neuropathy with neuromyotonia is a rare form of inherited peripheral neuropathy. This group of conditions affects an estimated 1 in 2,500 people. The prevalence of autosomal recessive axonal neuropathy with neuromyotonia is unknown.
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What are the genetic changes related to autosomal recessive axonal neuropathy with neuromyotonia ?
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Autosomal recessive axonal neuropathy with neuromyotonia is caused by mutations in the HINT1 gene. This gene provides instructions for making a protein that is involved in the function of the nervous system; however its specific role is not well understood. Laboratory studies show that the HINT1 protein has the ability to carry out a chemical reaction called hydrolysis that breaks down certain molecules; however, it is not known what effects the reaction has in the body. HINT1 gene mutations that cause autosomal recessive axonal neuropathy with neuromyotonia lead to production of a HINT1 protein with little or no function. Sometimes the abnormal protein is broken down prematurely. Researchers are working to determine how loss of functional HINT1 protein affects the peripheral nerves and leads to the signs and symptoms of this condition.
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Is autosomal recessive axonal neuropathy with neuromyotonia inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for autosomal recessive axonal neuropathy with neuromyotonia ?
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These resources address the diagnosis or management of autosomal recessive axonal neuropathy with neuromyotonia: - Genetic Testing Registry: Gamstorp-Wohlfart syndrome These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) malignant hyperthermia ?
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Malignant hyperthermia is a severe reaction to particular drugs that are often used during surgery and other invasive procedures. Specifically, this reaction occurs in response to some anesthetic gases, which are used to block the sensation of pain, and with a muscle relaxant that is used to temporarily paralyze a person during a surgical procedure. If given these drugs, people at risk for malignant hyperthermia may experience muscle rigidity, breakdown of muscle fibers (rhabdomyolysis), a high fever, increased acid levels in the blood and other tissues (acidosis), and a rapid heart rate. Without prompt treatment, the complications of malignant hyperthermia can be life-threatening. People at increased risk for this disorder are said to have malignant hyperthermia susceptibility. Affected individuals may never know they have the condition unless they undergo testing or have a severe reaction to anesthesia during a surgical procedure. While this condition often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease and multiminicore disease) are associated with malignant hyperthermia susceptibility.
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How many people are affected by malignant hyperthermia ?
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Malignant hyperthermia occurs in 1 in 5,000 to 50,000 instances in which people are given anesthetic gases. Susceptibility to malignant hyperthermia is probably more frequent, because many people with an increased risk of this condition are never exposed to drugs that trigger a reaction.
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What are the genetic changes related to malignant hyperthermia ?
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Variations of the CACNA1S and RYR1 genes increase the risk of developing malignant hyperthermia. Researchers have described at least six forms of malignant hyperthermia susceptibility, which are caused by mutations in different genes. Mutations in the RYR1 gene are responsible for a form of the condition known as MHS1. These mutations account for most cases of malignant hyperthermia susceptibility. Another form of the condition, MHS5, results from mutations in the CACNA1S gene. These mutations are less common, causing less than 1 percent of all cases of malignant hyperthermia susceptibility. The RYR1 and CACNA1S genes provide instructions for making proteins that play essential roles in muscles used for movement (skeletal muscles). For the body to move normally, these muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by the flow of certain charged atoms (ions) into muscle cells. The proteins produced from the RYR1 and CACNA1S genes are involved in the movement of calcium ions within muscle cells. In response to certain signals, the CACNA1S protein helps activate the RYR1 channel, which releases stored calcium ions within muscle cells. The resulting increase in calcium ion concentration inside muscle cells stimulates muscle fibers to contract. Mutations in the RYR1 or CACNA1S gene cause the RYR1 channel to open more easily and close more slowly in response to certain drugs. As a result, large amounts of calcium ions are released from storage within muscle cells. An overabundance of available calcium ions causes skeletal muscles to contract abnormally, which leads to muscle rigidity in people with malignant hyperthermia. An increase in calcium ion concentration within muscle cells also activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis). The genetic causes of several other types of malignant hyperthermia (MHS2, MHS4, and MHS6) are still under study. A form of the condition known as MHS3 has been linked to the CACNA2D1 gene. This gene provides instructions for making a protein that plays an essential role in activating the RYR1 channel to release calcium ions into muscle cells. Although this gene is thought to be related to malignant hyperthermia in a few families, no causative mutations have been identified.
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Is malignant hyperthermia inherited ?
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Malignant hyperthermia susceptibility is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of a severe reaction to certain drugs used during surgery. In most cases, an affected person inherits the altered gene from a parent who is also at risk for the condition.
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What are the treatments for malignant hyperthermia ?
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These resources address the diagnosis or management of malignant hyperthermia: - Gene Review: Gene Review: Malignant Hyperthermia Susceptibility - Genetic Testing Registry: Malignant hyperthermia susceptibility type 1 - Genetic Testing Registry: Malignant hyperthermia susceptibility type 2 - Genetic Testing Registry: Malignant hyperthermia susceptibility type 3 - Genetic Testing Registry: Malignant hyperthermia susceptibility type 4 - Genetic Testing Registry: Malignant hyperthermia susceptibility type 5 - Genetic Testing Registry: Malignant hyperthermia susceptibility type 6 - MedlinePlus Encyclopedia: Malignant Hyperthermia These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) medium-chain acyl-CoA dehydrogenase deficiency ?
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Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is a condition that prevents the body from converting certain fats to energy, particularly during periods without food (fasting). Signs and symptoms of MCAD deficiency typically appear during infancy or early childhood and can include vomiting, lack of energy (lethargy), and low blood sugar (hypoglycemia). In rare cases, symptoms of this disorder are not recognized early in life, and the condition is not diagnosed until adulthood. People with MCAD deficiency are at risk of serious complications such as seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death. Problems related to MCAD deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
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How many people are affected by medium-chain acyl-CoA dehydrogenase deficiency ?
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In the United States, the estimated incidence of MCAD deficiency is 1 in 17,000 people. The condition is more common in people of northern European ancestry than in other ethnic groups.
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What are the genetic changes related to medium-chain acyl-CoA dehydrogenase deficiency ?
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Mutations in the ACADM gene cause MCAD deficiency. This gene provides instructions for making an enzyme called medium-chain acyl-CoA dehydrogenase, which is required to break down (metabolize) a group of fats called medium-chain fatty acids. These fatty acids are found in foods and the body's fat tissues. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues. Mutations in the ACADM gene lead to a shortage (deficiency) of the MCAD enzyme within cells. Without sufficient amounts of this enzyme, medium-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to the characteristic signs and symptoms of this disorder such as lethargy and hypoglycemia. Medium-chain fatty acids or partially metabolized fatty acids may also build up in tissues and damage the liver and brain. This abnormal buildup causes the other signs and symptoms of MCAD deficiency.
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Is medium-chain acyl-CoA dehydrogenase deficiency inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for medium-chain acyl-CoA dehydrogenase deficiency ?
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These resources address the diagnosis or management of MCAD deficiency: - Baby's First Test - Gene Review: Gene Review: Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency - Genetic Testing Registry: Medium-chain acyl-coenzyme A dehydrogenase deficiency - MedlinePlus Encyclopedia: Newborn Screening Tests These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) congenital fibrosis of the extraocular muscles ?
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Congenital fibrosis of the extraocular muscles is a disorder that affects the muscles that surround the eyes. These muscles control eye movement and the position of the eyes (for example, looking straight ahead). Congenital fibrosis of the extraocular muscles prevents the normal development and function of these muscles. As a result, affected individuals are unable to move their eyes normally. Most people with this condition have difficulty looking upward, and their side-to-side eye movement may also be limited. The eyes may be misaligned such that they look in different directions (strabismus). Instead of moving their eyes, affected individuals may need to turn their head to track moving objects. Additionally, many people with congenital fibrosis of the extraocular muscles have droopy eyelids (ptosis), which further limits their vision. Researchers have identified at least four forms of congenital fibrosis of the extraocular muscles, designated CFEOM1, CFEOM2, CFEOM3, and Tukel syndrome. The specific problems with eye movement vary among the types. Tukel syndrome is characterized by missing fingers (oligodactyly) and other hand abnormalities in addition to problems with eye movement.
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How many people are affected by congenital fibrosis of the extraocular muscles ?
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CFEOM1 is the most common form of congenital fibrosis of the extraocular muscles, affecting at least 1 in 230,000 people. CFEOM1 and CFEOM3 have been reported worldwide, whereas CFEOM2 has been seen in only a few families of Turkish, Saudi Arabian, and Iranian descent. Tukel syndrome appears to be very rare; it has been diagnosed in only one large Turkish family.
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What are the genetic changes related to congenital fibrosis of the extraocular muscles ?
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CFEOM1 and rare cases of CFEOM3 result from mutations in the KIF21A gene. This gene provides instructions for making a protein called a kinesin, which is essential for the transport of materials within cells. Researchers believe that this protein plays an important role in the normal development and function of nerves in the head and face. In particular, this protein plays a critical role in the development of a particular branch of cranial nerve III, which emerges from the brain and controls muscles that raise the eyes and eyelids. Mutations in the KIF21A gene likely alter the protein's ability to transport materials within nerve cells, preventing the normal development of these cranial nerves and the extraocular muscles they control. Abnormal function of the extraocular muscles leads to restricted eye movement and related problems with vision. Mutations in the PHOX2A gene cause CFEOM2. This gene provides instructions for making a protein that is found in the developing nervous system. Studies suggest that the PHOX2A protein plays a critical role in the development of cranial nerves III and IV, which are necessary for normal eye movement. Mutations likely eliminate the function of the PHOX2A protein, which prevents the normal development of these cranial nerves and the extraocular muscles they control. In most cases of CFEOM3, the genetic cause of the condition is unknown. Studies suggest that a gene associated with CFEOM3 may be located near one end of chromosome 16. The gene associated with Tukel syndrome has not been identified either, although researchers think that it may be located near one end of chromosome 21.
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Is congenital fibrosis of the extraocular muscles inherited ?
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The different types of congenital fibrosis of the extraocular muscles have different patterns of inheritance. CFEOM1 and CFEOM3 are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In some cases, an affected person inherits the mutation from one affected parent. Other cases result from new mutations in the gene and occur in people with no history of the disorder in their family. CFEOM2 is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. Tukel syndrome also appears to have an autosomal recessive pattern of inheritance, although the genetic change responsible for this disorder is unknown.
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What are the treatments for congenital fibrosis of the extraocular muscles ?
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These resources address the diagnosis or management of congenital fibrosis of the extraocular muscles: - Gene Review: Gene Review: Congenital Fibrosis of the Extraocular Muscles - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 1 - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 2 - Genetic Testing Registry: Fibrosis of extraocular muscles, congenital, 3a, with or without extraocular involvement - Genetic Testing Registry: Tukel syndrome - MedlinePlus Encyclopedia: Extraocular Muscle Function Testing - MedlinePlus Encyclopedia: Strabismus These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) lysinuric protein intolerance ?
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Lysinuric protein intolerance is a disorder caused by the body's inability to digest and use certain protein building blocks (amino acids), namely lysine, arginine, and ornithine. Because the body cannot effectively break down these amino acids, which are found in many protein-rich foods, nausea and vomiting are typically experienced after ingesting protein. People with lysinuric protein intolerance have features associated with protein intolerance, including an enlarged liver and spleen (hepatosplenomegaly), short stature, muscle weakness, impaired immune function, and progressively brittle bones that are prone to fracture (osteoporosis). A lung disorder called pulmonary alveolar proteinosis may also develop. This disorder is characterized by protein deposits in the lungs, which interfere with lung function and can be life-threatening. An accumulation of amino acids in the kidneys can cause end-stage renal disease (ESRD) in which the kidneys become unable to filter fluids and waste products from the body effectively. A lack of certain amino acids can cause elevated levels of ammonia in the blood. If ammonia levels are too high for too long, they can cause coma and intellectual disability. The signs and symptoms of lysinuric protein intolerance typically appear after infants are weaned and receive greater amounts of protein from solid foods.
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How many people are affected by lysinuric protein intolerance ?
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Lysinuric protein intolerance is estimated to occur in 1 in 60,000 newborns in Finland and 1 in 57,000 newborns in Japan. Outside these populations this condition occurs less frequently, but the exact incidence is unknown.
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What are the genetic changes related to lysinuric protein intolerance ?
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Mutations in the SLC7A7 gene cause lysinuric protein intolerance. The SLC7A7 gene provides instructions for producing a protein called y+L amino acid transporter 1 (y+LAT-1), which is involved in transporting lysine, arginine, and ornithine between cells in the body. The transportation of amino acids from the small intestines and kidneys to the rest of the body is necessary for the body to be able to use proteins. Mutations in the y+LAT-1 protein disrupt the transportation of amino acids, leading to a shortage of lysine, arginine, and ornithine in the body and an abnormally large amount of these amino acids in urine. A shortage of lysine, arginine, and ornithine disrupts many vital functions. Arginine and ornithine are involved in a cellular process called the urea cycle, which processes excess nitrogen (in the form of ammonia) that is generated when protein is used by the body. The lack of arginine and ornithine in the urea cycle causes elevated levels of ammonia in the blood. Lysine is particularly abundant in collagen molecules that give structure and strength to connective tissues such as skin, tendons, and ligaments. A deficiency of lysine contributes to the short stature and osteoporosis seen in people with lysinuric protein intolerance. Other features of lysinuric protein intolerance are thought to result from abnormal protein transport (such as protein deposits in the lungs) or a lack of protein that can be used by the body (protein malnutrition).
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Is lysinuric protein intolerance inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for lysinuric protein intolerance ?
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These resources address the diagnosis or management of lysinuric protein intolerance: - Gene Review: Gene Review: Lysinuric Protein Intolerance - Genetic Testing Registry: Lysinuric protein intolerance - MedlinePlus Encyclopedia: Aminoaciduria - MedlinePlus Encyclopedia: Malabsorption These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) glycogen storage disease type IX ?
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Glycogen storage disease type IX (also known as GSD IX) is a condition caused by the inability to break down a complex sugar called glycogen. The different forms of the condition can affect glycogen breakdown in liver cells or muscle cells or sometimes both. A lack of glycogen breakdown interferes with the normal function of the affected tissue. When GSD IX affects the liver, the signs and symptoms typically begin in early childhood. The initial features are usually an enlarged liver (hepatomegaly) and slow growth. Affected children are often shorter than normal. During prolonged periods without food (fasting), affected individuals may have low blood sugar (hypoglycemia) or elevated levels of ketones in the blood (ketosis). Ketones are molecules produced during the breakdown of fats, which occurs when stored sugars are unavailable. Affected children may have delayed development of motor skills, such as sitting, standing, or walking, and some have mild muscle weakness. Puberty is delayed in some adolescents with GSD IX. In the form of the condition that affects the liver, the signs and symptoms usually improve with age. Typically, individuals catch up developmentally, and adults reach normal height. However, some affected individuals have a buildup of scar tissue (fibrosis) in the liver, which can rarely progress to irreversible liver disease (cirrhosis). GSD IX can affect muscle tissue, although this form of the condition is very rare and not well understood. The features of this form of the condition can appear anytime from childhood to adulthood. Affected individuals may experience fatigue, muscle pain, and cramps, especially during exercise (exercise intolerance). Most affected individuals have muscle weakness that worsens over time. GSD IX can cause myoglobinuria, which occurs when muscle tissue breaks down abnormally and releases a protein called myoglobin that is excreted in the urine. Myoglobinuria can cause the urine to be red or brown. In a small number of people with GSD IX, the liver and muscles are both affected. These individuals develop a combination of the features described above, although the muscle problems are usually mild.
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How many people are affected by glycogen storage disease type IX ?
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GSD IX that affects the liver is estimated to occur in 1 in 100,000 people. The forms of the disease that affect muscles or both muscles and liver are much less common, although the prevalence is unknown.
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What are the genetic changes related to glycogen storage disease type IX ?
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Mutations in the PHKA1, PHKA2, PHKB, or PHKG2 genes are known to cause GSD IX. These genes provide instructions for making pieces (subunits) of an enzyme called phosphorylase b kinase. The enzyme is made up of 16 subunits, four each of the alpha, beta, gamma, and delta subunits. At least two different versions of phosphorylase b kinase are formed from the subunits: one is most abundant in liver cells and the other in muscle cells. The PHKA1 and PHKA2 genes provide instructions for making alpha subunits of phosphorylase b kinase. The protein produced from the PHKA1 gene is a subunit of the muscle enzyme, while the protein produced from the PHKA2 gene is part of the liver enzyme. The PHKB gene provides instructions for making the beta subunit, which is found in both the muscle and the liver. The PHKG2 gene provides instructions for making the gamma subunit of the liver enzyme. Whether in the liver or the muscles, phosphorylase b kinase plays an important role in providing energy for cells. The main source of cellular energy is a simple sugar called glucose. Glucose is stored in muscle and liver cells in a form called glycogen. Glycogen can be broken down rapidly when glucose is needed, for instance to maintain normal levels of glucose in the blood between meals or for energy during exercise. Phosphorylase b kinase turns on (activates) the enzyme that breaks down glycogen. Although the effects of gene mutations on the respective protein subunits are unknown, mutations in the PHKA1, PHKA2, PHKB, and PHKG2 genes reduce the activity of phosphorylase b kinase in liver or muscle cells and in blood cells. Reduction of this enzyme's function impairs glycogen breakdown. As a result, glycogen accumulates in and damages cells, and glucose is not available for energy. Glycogen accumulation in the liver leads to hepatomegaly, and the liver's inability to break down glycogen for glucose contributes to hypoglycemia and ketosis. Reduced energy production in muscle cells leads to muscle weakness, pain, and cramping.
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Is glycogen storage disease type IX inherited ?
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GSD IX can have different inheritance patterns depending on the genetic cause of the condition. When caused by mutations in the PHKA1 or PHKA2 gene, GSD IX is inherited in an X-linked recessive pattern. These genes are located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. However, some women with one altered copy of the PHKA2 gene have signs and symptoms of GSD IX, such as mild hepatomegaly or short stature in childhood. These features are usually mild but can be more severe in rare cases. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. When the condition is caused by mutations in the PHKB or PHKG2 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for glycogen storage disease type IX ?
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These resources address the diagnosis or management of glycogen storage disease type IX: - Gene Review: Gene Review: Phosphorylase Kinase Deficiency - Genetic Testing Registry: Glycogen storage disease IXb - Genetic Testing Registry: Glycogen storage disease IXc - Genetic Testing Registry: Glycogen storage disease IXd - Genetic Testing Registry: Glycogen storage disease type IXa1 These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) carnitine palmitoyltransferase I deficiency ?
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Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The severity of this condition varies among affected individuals. Signs and symptoms of CPT I deficiency often appear during early childhood. Affected individuals usually have low blood sugar (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. People with CPT I deficiency can also have an enlarged liver (hepatomegaly), liver malfunction, and elevated levels of carnitine in the blood. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, seizures, coma, and sudden death. Problems related to CPT I deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.
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How many people are affected by carnitine palmitoyltransferase I deficiency ?
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CPT I deficiency is a rare disorder; fewer than 50 affected individuals have been identified. This disorder may be more common in the Hutterite and Inuit populations.
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What are the genetic changes related to carnitine palmitoyltransferase I deficiency ?
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Mutations in the CPT1A gene cause CPT I deficiency. This gene provides instructions for making an enzyme called carnitine palmitoyltransferase 1A, which is found in the liver. Carnitine palmitoyltransferase 1A is essential for fatty acid oxidation, which is the multistep process that breaks down (metabolizes) fats and converts them into energy. Fatty acid oxidation takes place within mitochondria, which are the energy-producing centers in cells. A group of fats called long-chain fatty acids cannot enter mitochondria unless they are attached to carnitine. Carnitine palmitoyltransferase 1A connects carnitine to long-chain fatty acids so they can enter mitochondria and be used to produce energy. During periods of fasting, long-chain fatty acids are an important energy source for the liver and other tissues. Mutations in the CPT1A gene severely reduce or eliminate the activity of carnitine palmitoyltransferase 1A. Without enough of this enzyme, carnitine is not attached to long-chain fatty acids. As a result, these fatty acids cannot enter mitochondria and be converted into energy. Reduced energy production can lead to some of the features of CPT I deficiency, such as hypoketotic hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and brain. This abnormal buildup causes the other signs and symptoms of the disorder.
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Is carnitine palmitoyltransferase I deficiency inherited ?
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This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
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What are the treatments for carnitine palmitoyltransferase I deficiency ?
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These resources address the diagnosis or management of CPT I deficiency: - Baby's First Test - FOD (Fatty Oxidation Disorders) Family Support Group: Diagnostic Approach to Disorders of Fat Oxidation - Information for Clinicians - Gene Review: Gene Review: Carnitine Palmitoyltransferase 1A Deficiency - Genetic Testing Registry: Carnitine palmitoyltransferase I deficiency These resources from MedlinePlus offer information about the diagnosis and management of various health conditions: - Diagnostic Tests - Drug Therapy - Surgery and Rehabilitation - Genetic Counseling - Palliative Care
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What is (are) neuromyelitis optica ?
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Neuromyelitis optica is an autoimmune disorder that affects the nerves of the eyes and the central nervous system, which includes the brain and spinal cord. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In neuromyelitis optica, the autoimmune attack causes inflammation of the nerves, and the resulting damage leads to the signs and symptoms of the condition. Neuromyelitis optica is characterized by optic neuritis, which is inflammation of the nerve that carries information from the eye to the brain (optic nerve). Optic neuritis causes eye pain and vision loss, which can occur in one or both eyes. Neuromyelitis optica is also characterized by transverse myelitis, which is inflammation of the spinal cord. The inflammation associated with transverse myelitis damages the spinal cord, causing a lesion that often extends the length of three or more bones of the spine (vertebrae). In addition, myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses, can be damaged. Transverse myelitis causes weakness, numbness, and paralysis of the arms and legs. Other effects of spinal cord damage can include disturbances in sensations, loss of bladder and bowel control, uncontrollable hiccupping, and nausea. In addition, muscle weakness may make breathing difficult and can cause life-threatening respiratory failure in people with neuromyelitis optica. There are two forms of neuromyelitis optica, the relapsing form and the monophasic form. The relapsing form is most common. This form is characterized by recurrent episodes of optic neuritis and transverse myelitis. These episodes can be months or years apart, and there is usually partial recovery between episodes. However, most affected individuals eventually develop permanent muscle weakness and vision impairment that persist even between episodes. For unknown reasons, approximately nine times more women than men have the relapsing form. The monophasic form, which is less common, causes a single episode of neuromyelitis optica that can last several months. People with this form of the condition can also have lasting muscle weakness or paralysis and vision loss. This form affects men and women equally. The onset of either form of neuromyelitis optica can occur anytime from childhood to adulthood, although the condition most frequently begins in a person's forties. Approximately one-quarter of individuals with neuromyelitis optica have signs or symptoms of another autoimmune disorder such as myasthenia gravis, systemic lupus erythematosus, or Sjgren syndrome. Some scientists believe that a condition described in Japanese patients as optic-spinal multiple sclerosis (or opticospinal multiple sclerosis) that affects the nerves of the eyes and central nervous system is the same as neuromyelitis optica.
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How many people are affected by neuromyelitis optica ?
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Neuromyelitis optica affects approximately 1 to 2 per 100,000 people worldwide. Women are affected by this condition more frequently than men.
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