Phosphoglycerate Kinase Deficiency

磷酸甘油酸激酶缺乏所致糖原贮积病

Phosphoglycerate kinase deficiency is an extremely rare inherited metabolic disorder characterized by deficiency of the enzyme phosphoglycerate kinase. This enzyme is essential for the breakdown of glycogen, resulting in the release of energy. Symptoms and findings associated with the disorder may include low levels of circulating red blood cells (hemolytic anemia); varying degrees of intellectual disability; rapidly changing emotions (emotional liability); an impaired ability to communicate through and/or to comprehend speech or writing (aphasia); exercise-induced pain, stiffness, or cramps; enlargement of the spleen (splenomegaly); and/or paralysis of one side of the body (hemiplegia). In most cases, phosphoglycerate kinase deficiency is inherited as an X-linked genetic trait. In such cases, the disorder is fully expressed in males only; however, some females who carry one copy of the disease gene (heterozygotes) may have hemolytic anemia.

The three main features of phosphoglycerate kinase deficiency are hemolytic anemia, intellectual disability, and muscle problems (myopathy). An individual with the disorder may be affected by one or more of these features, but it is unusual for one person to exhibit all three signs.

PGK is considered to be an inborn error of metabolism that is inherited in an X-linked manner. The gene responsible is located on the X chromosome (Xq13).

Phosphoglycerate kinase deficiency is a very rare disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygous carriers) may exhibit some symptoms associated with the disorder (i.e., hemolytic anemia). The disorder can be diagnosed at birth when enzymatic testing is done. More than 30 cases of PGK deficiency have been written up in the medical literature. It is thought that there are people with the disease who do not receive a diagnosis.

Symptoms of the following disorders can be similar to those of phosphoglycerate kinase deficiency. Comparisons may be useful for a differential diagnosis:

Warm antibody hemolytic anemia is an autoimmune disorder characterized by the premature destruction of red blood cells by the body’s natural defenses against invading organisms (antibodies). The severity of the anemia is determined by the amount of time the red blood cells survive. (For more information on this disorder, choose Warm Antibody, Hemolytic Anemia as your search term in the Rare Disease Database.)


Pierre Robin Sequence

罗宾序列-少指畸形综合征

glossoptosis, micrognathia, and cleft palate

PRS involves physical changes during development that lead to altered oral cavity anatomy. Since air and food both pass through the mouth and down the throat, breathing and feeding problems are common.

At present, the exact cause of PRS is unknown. The most widely held view is that multiple contributing factors lead to a sequence of physical changes within the oral cavity. These changes are thought to occur in a series of steps, rather than as isolated events. Specifically, it is believed that failure of the lower jaw to fully develop early in gestation causes the tongue to be positioned toward the back and high up in the mouth cavity, which, in turn, prevents palate closure.

PRS affects males and females in equal numbers, with an estimated prevalence of about 1 in 8,500-14,000 individuals.

Symptoms of the following disorders can be similar to, or may be associated with, PRS. Comparisons may be useful for a differential diagnosis.

PRS can be detected while the fetus is still in the womb. Trained medical personnel may visualize characteristic features of PRS using ultrasound imaging. If not diagnosed previously, craniofacial abnormalities are typically detected at birth on physical exam. Infants with severe airway obstruction may present with respiratory distress at birth, and may require medical intervention.


PIK3CA-related overgrowth syndrome

PIK3CA基因相关生长过度综合征

Different subtypes within PROS include: CLAPO syndrome, CLOVES syndrome, DCMO, DMEG, FAH/FAO/HHML, FAVA, FIL, HMEG, Klippel-Trenaunay syndrome (KTS), LON, macrodactyly, MCAP and muscular hemihyperplasia (HH). Symptoms vary widely and depend on which part of the body overgrows, ranging from intellectual disability, seizures and autism when the brain is involved to blood clots when blood vessels are affected. Some PROS syndromes affect a wider range of body systems while others are more limited in which parts of the body overgrow.

PROS is caused by somatic mutations in the PIK3CA gene. There are a variety of activating mutations of the PIK3CA gene associated with each syndrome with some genetic overlap between the different syndromes.

Because PROS includes several different syndromes, the exact incidence and prevalence rates are not known. These syndromes are typically diagnosed at birth or in early childhood. Many syndromes such as MCAP, CLOVES and KTS affect males and females in equal numbers.

Proteus syndrome is a rare disorder characterized by asymmetric, patchy overgrowth of various tissues of the body. The cause of the disorder is a mosaic variant in a gene called AKT1 instead of PIK3CA as in PROS. (For more information on this disorder, choose Proteus Syndrome as your search term in the Rare Disease Database).

Diagnosis of PROS is based on genetic testing for PIK3CA genetic variants. Testing for somatic conditions includes biopsy of tissue affected by overgrowth. Detection of a PIK3CA mutation in biopsied tissue may be difficult because these mutations are detected at widely varying levels in affected cells and tissues.

Treatment depends on symptoms present for each syndrome and, for those patients with multiple features, requires collaboration between an interdisciplinary team of physicians and specialists.


Pitt-Hopkins Syndrome

With the publication of an increasing number of case series we are developing a better picture of associated symptoms and prognosis of individuals with Pitt-Hopkins syndrome. However, much about the disorder is not fully understood. It is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.

Pitt-Hopkins syndrome is caused by an unexpected change (mutation) in the TCF4 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body, including the brain. The TCF4 gene creates a protein that is a transcription factor. This protein has an important role in various developmental processes of the body. It is highly expressed early during human development and is found throughout the central nervous system.

Pitt-Hopkins syndrome affects both males and females and can affect individuals of any ethnic or racial background. The exact incidence of the disorder is unknown. Approximately 500 affected individuals have been identified worldwide. Researchers believe that affected individuals often go undiagnosed or misdiagnosed, making it difficult to determine the true frequency the disorder in the general population. Intellectual disability (due to all causes) affects approximately 1%-3% of the general population.

Symptoms of the following disorders can be similar to those of Pitt-Hopkins syndrome. Comparisons may be useful for a differential diagnosis.

A diagnosis of Pitt-Hopkins syndrome depends upon a detailed patient history, a thorough clinical evaluation, and identification of characteristic symptoms. There is overlap among symptoms associated with Pitt-Hopkins syndrome and other similar neurological disorders. The lack of major congenital malformations, which are structural or functional abnormalities that are present at birth, supports a diagnosis, which can generally be confirmed by molecular testing demonstrating a specific change (mutation) or deletion involving the TCF4 gene. This gene is often included on gene panels that can be ordered for individuals with features of Pitt-Hopkins/Rett/Angelman syndromes. There are individuals with clinical features that can’t be distinguished from Pitt-Hopkins syndrome for which no mutation in TCF4 can be found, and some individuals with variants in TCF4 with a phenotype differing from Pitt-Hopkins syndrome. Diagnostic criteria have been published based on published cases, but are being redefined as more molecularly confirmed cases have been identified.

Treatment is directed toward the specific symptoms that are apparent in each individual and generally requires a team of specialists, that can be coordinated by a medical geneticist or your pediatrician. Members of this team may include a pediatric neurologist (a physician who specializes in the diagnosis and treatment of disorders of the brain, nerves and nervous system in children), a gastroenterologist (a physician who specializes in the diagnosis and treatment of disorders of the gastrointestinal tract), an ophthalmologist (a physician who specializes in the diagnosis and treatment of disorders of the eye), a pulmonologist (a physician who specializes in the diagnosis and treatment of disorders of the lungs and breathing issues), a speech pathologist, psychologist, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Genetic counseling is of benefit for affected individuals and their families. Psychosocial support for the entire family is essential as well.


Pityriasis Rubra Pilaris

The terms sign and symptom are not redundant. SIGN is an indication of a medical condition that can be objectively observed by others, including healthcare professionals. In contrast, a SYMPTOM is subjective, information that is shared by the PRP patient with the healthcare provider such as pain, itching, fatigue. The following is a list of signs and symptoms that define PRP.

The specific underlying cause of PRP is unknown, although a combination of a genetic predisposition, environmental trigger, and other unknown causes is believed to play key roles. Vitamin A deficiency was once believed to be related to the disorder, however, this theory lacks sufficient evidence and treatment with Vitamin A has been less than effective.36, 38

Based on conversations within the PRP community, we can say with metaphysical certitude that PRP isn’t a punishment for misbehavior or forgetting to put the toilet seat down. There are thousands of perfectly wonderful people who have — or had — PRP. Moreover, there are many very bad people who don’t have it. Who then gets the short end of this rare disease stick?

Symptoms of the following disorders can be similar to those of pityriasis rubra pilaris. Comparisons may be useful for a differential diagnosis:

Psoriasis: According to the National Psoriasis Foundation (NPF), Psoriasis is an immune-mediated disease that causes raised, red, scaly patches to appear on the skin. It typically affects the outside of the elbows, knees or scalp, though it can appear on any location. Some people report that psoriasis is itchy, burns and stings. Psoriasis is associated with other serious health conditions, such as diabetes, heart disease and depression. More information is available at the NPF website.26


PLA2G6-associated neurodegeneration

PLA2G6基因相关神经退行性变

INAD and other forms of PLAN are inherited in an autosomal recessive pattern. Variants of the PLA2G6 gene cause PLAN.

PLAN is an extremely rare genetic disorder, and the incidence and prevalence are not known with any certainty. It is estimated to occur in about 1-2/million children.

Symptoms of the following disorders may be similar to those of PLAN. Comparisons may be useful while investigating diagnoses.

PLAN is diagnosed by means of a thorough clinical evaluation, brain MRI, a detailed history, and a variety of specialized tests including molecular genetic testing to sequence the PLA2G6 gene. A diagnosis of PLAN is confirmed by finding two changes in the PLA2G6 gene that are predicted to affect how it works or have been documented in other patients with PLAN. If no gene variant or only one gene variant is found through sequencing analysis of the PLA2G6 gene, then genetic testing may proceed to deletion/duplication analysis. This looks for large pieces of the gene that may be extra or missing, which sequencing can miss. Among individuals who go forward with deletion/duplication analysis, a gene change may be found in ~ 12.5 % of patients.


Plague

Plague is an acute, severe infectious disease caused by the bacterium Yersinia pestis. The bacterium is found in fleas and wild rodents such as rats, squirrels, chipmunks or prairie dogs. Plague is a zoonotic disease, which means it can be transmitted to humans through animals, most often through the bites of fleas or through direct contact with infected animal tissue. The disease is most common in parts of Africa, Asia and South America, but it also occurs in some areas of the western United States. Symptoms can include an abrupt onset of chills, fever, and enlarged, painful lymph nodes (buboes). Most cases of plague resolve with effective treatment, though treatment must be started immediately to avoid life-threatening complications. Although plague is extremely rare in the United States, interest in the infection has heightened in recent years because of its potential use as an agent of biological warfare.

The symptoms of plague vary greatly depending upon the specific form that develops. The main clinical forms of plague are bubonic, septicemic, and pneumonic.

Plague is caused by infection with the bacterium Yersinia pestis. This bacterium is found in wild rodents and their fleas. Some of the most commonly infected rodents are rats, squirrels, chipmunks or prairie dogs. Rabbits and hares (lagomorphs) may also carry the bacteria. The disease is most often transmitted to humans by the bite of infected fleas. Less frequently, direct contact with infectious animal tissue can also result in infection.

Plague affects both males and females of all ages; however, historically it is slightly more common among men. Men may be more likely to become infected with plague because they are more likely to engage in outdoor activities that put them at risk (https://www.cdc.gov/plague/maps/index.html). Seven human plague cases are reported on average in the United States each year. Most cases in the United States occur in the Western and Southwestern part of the country, especially in New Mexico, Colorado, Arizona and California (https://www.cdc.gov/plague/maps/index.html). Plague has a scattered worldwide distribution. Most cases occur in sub-Saharan Africa, but plague still occurs on most continents. Historically, plague has caused massive pandemics most notably the Black Death of the Middle Ages.

Symptoms of the following disorders can be similar to those of the plague. Comparisons may be useful for a differential diagnosis.

The diagnosis of plague may be confirmed by specialized laboratory tests in addition to characteristic clinical findings. Yersinia pestis can be identified in blood samples, tissue taken from enlarged lymph nodes (buboes) and sputum. All suspected cases of plague in the United States must be reported to the appropriate local and/or state health department, which in turn notifies the Centers for Disease Control and Prevention (CDC).


Pleuropulmonary Blastoma

Two different sets of symptoms are found in children with PPB, based generally on the child’s age and the type of PPB:

Sometimes PPB occurs without any other conditions in the individual or family. PPB may also be an indication of an underlying variation in a gene called DICER1 (see Related Disorders).

PPB occurs in boys and girls approximately equally. Children under the age of 7-8 years are most often affected, but rarely teenagers or young adults may be diagnosed with PPB. Other conditions sometimes associated with PPB may be seen in individuals throughout the life span (see Related Disorders).

Individuals with PPB may have variants in the DICER1 gene. When a gene variant alters the function of the gene, there is an increased risk for PPB and a variety of other conditions including lung cysts, kidney cysts or tumors, ovarian tumors in children or adults, thyroid nodules or cancers, certain childhood brains and rarely, tumors in the eye or nose/sinuses. All of these are in the DICER1– related spectrum of diseases and conditions. It should be emphasized that many children and adults in these families have no medical problems.

When a child presents with symptoms of PPB, a chest X-ray may show an air-filled pocket (cyst) or a solid mass. Chest CT may be performed to look at the lungs in more detail. Surgery, either a biopsy or removal of the cyst or mass, is performed to diagnose and often remove the tumor. Microscopic examination of the specimen is needed. Review by the International PPB/DICER1 Registry pathology specialists may be helpful in confirming the diagnosis. This is offered at no cost to families or hospitals.


carbohydrate-deficient glycoprotein syndrome, type Ia

In order to help characterize and clarify this disorder, researchers have divided PMM2-CDG into three stages. These stages are based upon the symptoms at different periods of life. They are: the infantile multisystem stage; the late-infantile and childhood ataxia-intellectual disability stage; and the adult stable disability stage.

PMM2-CDG is caused by mutations of the PMM2 gene and is inherited as an autosomal recessive genetic trait. The malfunctioning PMM2 gene has been tracked to gene map locus chromosome 16p13.3-p13.2.

PMM2-CDG is the most common of a growing family of more than 100 extremely rare inherited metabolic disorders. More than 800 cases of this specific disorder have been reported worldwide. Two other disorders in this family are each represented by more than 20 cases. The remaining disorders in this family have fewer than 20 cases with several earning a place in the medical literature based on the report of one or two cases. The exact incidence and prevalence of these disorders in the general population is unknown. It is difficult to determine the true frequency of PMM2-CDG in the general population since the disorder may still be under-recognized and under-diagnosed in many parts of the world.

Symptoms of the following disorders can be similar to those of PMM2-CDG. Comparisons may be useful for a differential diagnosis.

A diagnosis of PMM2-CDG may be suspected based upon the identification of characteristic symptoms, a detailed patient history and a thorough clinical evaluation. A variety of specialized tests may be necessary to confirm a diagnosis of PMM2-CDG.


POEMS syndrome

POEMS syndrome is a rare, multisystem paraneoplastic syndrome. POEMS stands for some of the major signs and symptoms associated with the disease. The major criteria for POEMS syndrome include polyneuropathy, monoclonal gammopathy and either osteosclerotic lesion, Castleman disease, or elevated levels of vascular endothelial growth factor (VEGF) in addition to at least one minor criterion listed below.

The exact cause of POEMS syndrome is unknown. POEMS syndrome is associated with an overproduction of molecules that promote inflammation through cell-to-cell communication (pro-inflammatory cytokines). Studies have demonstrated abnormally high levels of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines, interleukin-6, interleukin-1 and TNF-alpha in the blood of individuals with POEMS syndrome. Cytokines are proteins that are produced by the body’s immune system in response to inflammation. More research is needed to determine the exact role cytokines and VEGF play in the development of POEMS syndrome.

POEMS syndrome affects 1.5 times more men than women, and disease onset usually occurs during a patient’s 40s to 60s. POEMS syndrome often goes unrecognized, making it difficult to determine the number of people afflicted with the disease.

Symptoms of the following disorders can be similar to those of POEMS syndrome. Comparisons may be useful for a differential diagnosis:

Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder in which there is swelling of nerve roots and peripheral nerves as well as destruction of the fatty protective covering (myelin sheath) of the nerves. This disorder causes weakness, paralysis and/or impairment in motor function, especially of the arms and legs. Sensory loss may also be present causing numbness, tingling or prickling sensations in affected areas. The motor and sensory impairments are usually on both sides of the body (symmetrical) and the degree of severity and disease course may vary. Some affected individuals may follow a slow steady pattern of symptoms while others may have symptoms that stabilize and relapse. A distinct feature of CIDP is that most patients cannot identify a preceding viral infection or illness. (For more information on this disorder, choose chronic inflammatory demyelinating polyneuropathy as your search term in the Rare Disease Database.)


Poland syndrome

Poland Syndrome is a rare condition that is evident at birth (congenital). Associated features may be extremely variable from case to case. However, it is classically characterized by absence (aplasia) of chest wall muscles on one side of the body (unilateral) and abnormally short, webbed fingers (symbrachydactyly) of the hand on the same side (ipsilateral).

Associated symptoms and findings are extremely variable, including in rare cases in which more than one family member has been affected. For example, in some reported cases, one sibling has had all major features of the condition, while the other sibling has had only absence of pectoral muscle or hand involvement.

According to reports in the medical literature, an overwhelming majority of cases appear to occur randomly for unknown reasons (sporadically) in the absence of a family history. However, in some very rare cases, familial patterns have been reported, including occurrence of the condition in a parent and child and in siblings born to unaffected parents. Some researchers suggest that apparently familial cases may result from inherited susceptibility to a certain event or anomaly (such as early interruption of blood flow) that may predispose to the syndrome (see directly below).

Poland Syndrome was named for the investigator (Poland A) who initially described the condition in 1841. According to reports in the medical literature, Poland Syndrome appears to be three times as common in males as females. Estimates of its incidence have ranged from approximately one in 10,000 to one in 100,000 individuals. (Incidence refers to the number of new cases in a particular period.)

Symptoms of the following disorders may be similar to those of Poland Syndrome. Comparisons may be useful for a differential diagnosis:

Several investigators have reported cases in which the features of Poland Syndrome occur in association with Moebius Syndrome. Known as Poland-Moebius Syndrome, such cases are characterized by facial paralysis due to impairment of the sixth and seventh cranial nerves (i.e., Moebius Syndrome) associated with the chest wall defects and/or hand malformations (symbrachydactyly) typically seen in Poland Syndrome. Moebius Syndrome may be characterized by a masklike, expressionless face; inability to conduct certain eye movements; drooping of the upper eyelids (ptosis); underdevelopment and/or limited mobility of the tongue; poor sucking and swallowing; and speech impairment. Additional features may include a deformity in which the foot is twisted out of shape or position (clubfoot); various other limb defects; mild mental retardation; and/or other abnormalities. Moebius Syndrome typically appears to occur randomly for unknown reasons (sporadically). As mentioned above (see Causes), some investigators suggest that the condition may result from early disruption of blood flow through particular arteries during embryonic development (i.e., Subclavian Artery Supply Disruption Sequence). (For more information on this condition, choose Moebius as your search term in the Rare Disease Database.)


Polyarteritis nodosa

Polyarteritis nodosa is a rare multi-system disorder characterized by widespread inflammation, weakening, and damage to small and medium-sized arteries. Blood vessels in any organ or organ system may be affected, including those supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles. Damage to affected arteries may result in abnormally increased blood pressure (hypertension), ballooning (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas.

Polyarteritis nodosa mainly affects small and medium-sized arteries.  Blood vessels in any organ or organ system may be affected, including arteries supplying the kidneys, heart, intestine, nervous system, and/or skeletal muscles.  Damage to affected arteries may result in abnormally increased blood pressure (hypertension), ballooning (aneurysm) of an arterial wall, the formation of blood clots (thrombosis), obstruction of blood supply to certain tissues, and/or tissue damage and loss (necrosis) in certain affected areas. Joint, muscle, abdominal and testicular pain may occur.  The small and medium-sized arteries of the kidneys are most often involved.  The lungs are much less commonly affected.

The exact cause of polyarteritis nodosa is not known.  In the majority of patients no predisposing cause has been found.  Unidentified bacterial and/or viral infections may be a cause.  Polyarteritis nodosa has been observed in drug abusers, particularly those using amphetamines, and in patients with hepatitis B (infection of the liver).  (For more information on this disorder, choose Hepatitis B as your search term in the Rare Disease Database.)  This disorder has also been linked to an allergic reaction to some drugs and vaccines.

Polyarteritis nodosa usually affects people between 40 and 50 years of age, but it may occur in any age group.  It affects approximately 1 in 100,000 people. Men appear to be affected two to three times more often than women.

Symptoms of the following disorders can be similar to those of polyarteritis nodosa.  Comparisons may be useful for a differential diagnosis:

Microscopic polyangiitis (formerly known as microscopic polyarteritis) can have inflammation of arteries that is clinically and pathologically indistinguishable from polyarteritis nodosa, but, unlike polyarteritis nodosa, this form of systemic vasculitis also has inflammation of vessels smaller than arteries, including arterioles, capillaries and venules. This small vessel involvement often involvers the venules in the skin (causing hemorrhage called purpura), capillaries in the lungs (causing pulmonary hemorrhage) and capillaries in the filters of the kidneys (causing glomerulonephritis).  Microscopic polyangiitis is closely related to Wegener’s granulomatosis and Churg-Strauss syndrome; and all three are associated with anti-neutrophil cytoplasmic autoantibodies (ANCA) in the blood.


Isolated polycystic liver disease

Polycystic liver disease is characterized by the growth of more than 10 cysts in the liver, ranging in size from a few millimeters to over 15 cm in diameter. Symptoms usually begin to show in the third decade, as cysts grow and increase in number with age. Some people begin to have symptoms in early adulthood, but many affected individuals do not have symptoms. The growth and accumulation of cysts can cause enlargement of the liver (hepatomegaly) and compression of adjacent anatomical structures, leading to abdominal pain and discomfort, shortness of breath (dyspnea), indigestion (dyspepsia), gastro-esophageal reflux and limited mobility. More rarely, liver cysts can also compress the bile duct and lead to yellowing of the skin (jaundice). Compression of the blood vessels of the liver by cysts can lead to accumulation of fluid in the abdomen (ascites), bleeding and high blood pressure in the blood flow from intestines to the liver (portal hypertension). In rare cases, patients can suffer from cyst bleeding (hepatic cyst hemorrhage) or a cyst can be infected by bacteria (hepatic cyst infection), causing pain and fever. Infrequently, large liver cysts may rupture, causing severe abdominal pain. Even with the presence of many cysts, the liver of individuals with polycystic liver disease functions normally.

Changes (mutations or pathogenic variants) in many different genes can cause ADPLD. Mutations in PRKCSH cause about 20% of cases and mutations in SEC6 cause about 15% of cases. Other genes associated with ADPLD include ALG8, GANAB, LRP5, PKHD and SEC61B3. However, less than 50% of individuals with polycystic liver disease have a mutation in one of these genes, so other genes may be involved in this condition.

Polycystic liver disease is estimated to affect less than 1 in 10,000 people. This is likely an underestimate because many people with the condition do not have symptoms. Males and females are affected in equal numbers, but most patients with symptoms and with severe disease are women. The suggested cause of this difference is that female sex hormones, such as estrogen, contribute to growth of liver cysts. Oral contraceptives and estrogen replacement therapy are also associated with more severe disease]. Cysts can begin to grow at any age but are rare in childhood and more common with age. The age at which symptoms begin to occur varies with individuals but is usually after 30 years old.

Symptoms of the following disorders can be similar to those of polycystic liver disease. Comparisons may be useful for a differential diagnosis:

Caroli syndrome is a rare congenital liver disorder characterized by enlargement (dilation) of the small branches of the bile ducts inside the liver. If symptoms occur, the most common are abdominal pain, fever and jaundice. Caroli syndrome is often associated with autosomal recessive polycystic kidney disease (ARPKD). (For more information on this disorder, choose Caroli as your search term in the Rare Disease Database.).


Polycythemia vera

The symptoms of polycythemia vera usually develop slowly over many years. Often, the disorder is found incidentally on a blood test as part of a routine exam before noticeable symptoms occur. Occasionally, affected individuals may report vague, nonspecific symptoms that eventually lead to diagnosis of the disorder.

Polycythemia vera is caused by a malignant change in the genetic material (DNA) within a single cell of the bone marrow (clonal disorder). Bone marrow is the soft, spongy material found inside bone where most blood cell production occurs. The underlying reason why this malignant change occurs is unknown.

Polycythemia vera affects slightly more males than females. The disorder is estimated to affect approximately 44 to 57 per 100,000 people in the US. It occurs most often in individuals more than 60 years old but can affect individuals of any age. It is extremely rare in individuals under 20.

Symptoms of the following disorders can be similar to those of polycythemia vera. Comparisons may be useful for a differential diagnosis.

Diagnosis of polycythemia vera may be made based upon a thorough clinical evaluation, detailed patient history and various specialized tests. In many people, the disorder may be detected from blood tests conducted during a routine examination. A complete blood count (CBC) may demonstrate elevated numbers of red blood cells and sometimes platelets and white blood cells.


Polymorphous Low-Grade Adenocarcinoma

Lobular Carcinoma of the Minor Salivary Glands

Polymorphous low-grade adenocarcinoma (PLGA) is a rare tumor of the salivary glands that is limited, to a great extent, to the minor salivary glands and commonly, but not exclusively, localized in the palate of the mouth. The major salivary glands are the parotid glands (at the side of the face, below the ears), the sublingual glands (below the tongue), and the submandibular glands (below the lower jaw).  As the name suggests, each of the major salivary glands is of substantial size and visible to the naked eye. There are about 600 to 1,000 minor salivary glands that are microscopic in size. These minor salivary glands are found in the lining (mucosa) of the lips, tongue, and hard and soft palate, as well as inside the nose, cheeks, and sinuses.

A lump or mass in the palate or near any of the salivary glands should be seen by a physician as soon as possible.  A lingering pain in the area of the salivary glands is a signal to see a physician.  A change in the size and/or shape of one of the salivary glands (asymmetry) may be a sufficient reason to see a doctor.  Unexplained bleeding in the mouth is also a symptom warranting attention, and any persistent numbness on any part of the face or a weakening of the muscles on one side of the face should be brought to the attention of a physician.  Early diagnosis and treatment are important.

Why a normal cell becomes malignant is not yet fully understood.

In most instances PLGA affects people in their middle age.  The median age at which patients are diagnosed is 57 years, with a range of from 22 to 71 years.  For reasons that are unknown, this disease affects slightly more women than men.

The diagnosis of PLGA may be suspected on history and clinical examination, but can be confirmed only by biopsy of the affected tissue.


Polymyalgia Rheumatica

Polymyalgia rheumatica is a rare inflammatory disease characterized by muscle pain (myalgia), stiffness, and additional generalized systemic symptoms such as fatigue, low-grade fever, and/or a general feeling of ill health (malaise). Polymyalgia rheumatica can be a relatively benign condition that is extremely responsive to treatment. In some rare cases, permanent muscle weakness, degeneration and loss (atrophy) of muscle mass, and disability may occur. The exact cause of polymyalgia rheumatica is unknown, although immunological factors and familial tendencies (genetic predisposition) have been mentioned in the medical literature.

In most cases, the symptoms of polymyalgia rheumatica begin abruptly (acutely). However, symptoms may develop slowly (insidiously) during a period of several weeks or months. Symptoms may include muscle pain (myalgia) and stiffness in the neck, shoulders, upper arms, lower back, hips, and/or thighs. The lower arms, hands, lower legs, and feet (distal extremities) are not usually affected by this disorder. Stiffness and pain, which typically occur on both sides of the body (bilateral), are most severe in the morning (morning stiffness) and after long periods of rest or inactivity (gel phenomenon). In most cases, the shoulder girdle is the first area affected. However, in other cases, the neck or hips may show the first signs of the disorder. Pain or discomfort usually begins on one side of the body before affecting the other side as well.

The exact cause of polymyalgia rheumatica is not known. The immune system has been implicated in some studies, but a direct relationship has not been established. Autoimmune disorders are caused when the body’s natural defenses against foreign or invading organisms (e.g., antibodies) begin to attack healthy tissue for unknown reasons. In addition, because the disorder occurs in older individuals, polymyalgia rheumatica may be related to the aging process.

Polymyalgia rheumatica is a rare disorder that affects twice as many females as males. Affected individuals are usually over the age of 50 years. This disorder occurs at the rate of about 50 per 100,000 in people over 50 years of age. Polymyalgia rheumatica is estimated to affect 450,000 individuals in the United States.

Symptoms of the following disorders can be similar to those of polymyalgia rheumatica. Comparisons may be useful for a differential diagnosis:

Giant cell arteritis, also known as temporal arteritis, is a chronic inflammatory disorder characterized by the progressive inflammation of many arteries of the body (panarteritis). Granular material and abnormally large cells (giant cells) accumulate in the elastic lining of the arteries. Symptoms of giant cell arteritis vary widely from case to case. In some cases, chronic inflammation is confined to the different branches of the heart’s main artery (aorta), resulting in many large arteries becoming inflamed. However, the temporal arteries in the head are most frequently affected, causing symptoms such as headaches and stabbing pain on both sides of the head. The scalp of some affected individuals may also become red, swollen, and/or tender. Some affected individuals may also feel rhythmic pulsations on either side of the head. Additional symptoms may include fever, muscles weakness, a general feeling of ill health (malaise), muscle pain, weight loss, and stiffness. Some individuals with giant cell arteritis may develop polymyalgia rheumatica. (For more information on this disorder, choose Giant Cell Arteritis as your search term in the Rare Disease Database.)


前阿黑皮素缺乏所致肥胖症

Obesity due to pro-opiomelanocortin deficiency

obesity due to pro-opiomelanocortin deficiency

Most individuals diagnosed with POMC deficiency have early-onset obesity and adrenal insufficiency, a condition in which the adrenal glands don’t work correctly. The first symptom of POMC deficiency is often very low blood sugar (hypoglycemia) related to adrenal insufficiency and low levels of ACTH, an important hormone made by the pituitary. ACTH is necessary for the adequate production of cortisol in the adrenal gland. If left untreated, adrenal insufficiency may lead to liver failure and less commonly, death. Infants with POMC deficiency have a normal birth weight but are constantly hungry (hyperphagia) and gain weight very quickly. Obesity is common by age one. Children and adults with this condition have continuous hunger, obesity and behavior problems related to food and eating. Obesity may become severe, leading to other health problems. Some people have a low functioning thyroid gland and are shorter than average. Delayed or absent puberty has also been reported. Many people with POMC deficiency also have pale skin and light or red hair.

POMC deficiency is caused by pathogenic variants (mutations) in the POMC gene. The POMC gene works with other genes to help signal the body when it’s time to eat and when it has had enough food. When the POMC gene doesn’t work correctly, these signals don’t exist and a person with POMC deficiency feels hungry all the time. In addition, the protein made by the POMC gene affects other glands in the body, especially the adrenal gland, thyroid and liver.

POMC deficiency is very rare, and it is unclear if it is more common in any particular populations. It has been diagnosed more often in populations where marriage between relatives is customary.

POMC deficiency is one of several rare inherited conditions that include early-onset obesity with few or no other signs or symptoms. These conditions are due to changes in one of the genes that normally work together to help regulate hunger and energy production. These conditions may be difficult to diagnose based solely on clinical examination. Adrenal insufficiency and pale skin and hair may set POMC deficiency apart from other early-onset obesity conditions, but often genetic testing is the only way to tell the difference between them.

POMC deficiency is diagnosed based on a clinical examination, symptoms and the results of laboratory and genetic testing. POMC deficiency is usually diagnosed after adrenal insufficiency is confirmed and obesity develops. The diagnosis of POMC deficiency is confirmed using genetic testing for variants in the POMC gene.

Early treatment options for obesity for people with POMC deficiency include weight management through diet and behavioral counseling, physical training and outpatient obesity programs. However, most of these do not result in permanent weight loss.


酸性麦芽糖酶缺乏所致糖原贮积病

Glycogen storage disease due to acid maltase deficiency

glycogen storage disease type II (GSD II)

Patients with the ‘classic infantile’ form of Pompe disease are the most severely affected. Although hardly any symptoms may be apparent at birth, the disease usually presents within the first three months of life with rapidly progressive muscle weakness (‘floppy infants’), diminished muscle tone (hypotonia), respiratory deficiency, and a type of heart disease known as hypertrophic cardiomyopathy, a condition characterized by abnormal thickening of the walls of the heart (mainly the left chamber and the wall between the left and right chamber) resulting in diminished cardiac function. These problems together culminate in cardio-respiratory failure within the first 2 years of life.

Pompe disease is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease. Pompe disease carriers will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

Pompe disease occurs in various populations and ethnic groups around the world. Estimates vary, but its incidence is generally placed at approximately 1 in 40,000 births in the United States (and in the Netherlands). However, a recent review of birth incidences in Missouri reported a much higher incidence of 1 in 5,463 in that state. A ‘founder effect’ cannot be excluded. The same holds for Pompe disease in the American Black population and for Pompe disease in Taiwan where unique pathogenic variants have been reported.

A variety of disorders can cause symptoms or physical findings that are like those seen in individuals with Pompe disease. Several of these disorders are discussed below. For more information on these disorders, choose the specific disorder name as your search term in the NORD Rare Disease Database.

Most physicians are not familiar with Pompe disease. They may never have had patients with Pompe Disease. They need to know what they are looking for. The diagnosis of Pompe disease is based on a thorough clinical evaluation, a detailed patient and family history, and a variety of biochemical tests with first of all the measuring of GAA activity. Preimplantation testing and prenatal diagnosis are also possible when a pregnancy is known to be at risk for Pompe disease.


非综合征型脑桥小脑发育不全

Pontocerebellar hypoplasias (PCH) are a group of rare heterogeneous conditions characterized by prenatal development of an abnormally small cerebellum and brain stem, which is usually associated with profound psychomotor retardation. Although the clinical features vary widely, pontocerebellar hypoplasias are usually associated with profound intellectual disability and delayed or absent psychomotor milestones. In most cases, the disease is uniformly fatal early in life. Life span has ranged from death in the perinatal period to about 20-25 years of age. Only a few individuals-usually patients with PCH type 2-have survived to the second and third decades of life. At least 6 types of PCH have been described and a few rare variants are now being identified.

Pontocerebellar Hypoplasia Type 1 (PCH type 1):

Pontocerebellar hypoplasia is considered to be inherited as an autosomal recessive disorder because it occurs mostly in consanguineous families (families where both parents are related). Therefore, each offspring of parents carrying the genetic abnormality has a one in four chance of suffering from pontocerebellar hypoplasia. However there is a two out of three chance that a sibling of an affected child may have one of the abnormal genes that on its own will not cause the disease in that sibling. Brain imaging (MRI or CT) shows small cerebellum and pons.

The disease affects both males and females without a predilection for either sex. More than 100 cases have been reported in the medical literature. The exact incidence of pontocerebellar hypoplasia is unknown.

Symptoms of the following disorders can be similar to those of PCH. Comparisons may be useful for a differential diagnosis.

Molecular genetic diagnosis is available and has been described above with each PCH type for which it is available. Genetic tests are available for PCH types 1, 2A, 2B, 2C, 4 and 6. Prenatal diagnosis is now available for some forms of PCH.


Porphyria cutanea tarda

The symptoms of PCT can vary greatly from one individual to another. Skin abnormalities characterize this disorder. Affected individuals are abnormally susceptible to damage of the skin from sunlight (photosensitivity). Extremely fragile skin that can peel or blister on minimal impact is common. Affected individuals may develop blistering skin lesions on areas of the skin that are frequently exposed to the sun such as the hands and face. These lesions may crust over.

PCT is a multifactorial disorder, which means that several different factors such as genetic and environmental factors occurring in combination are necessary for the development of the disorder. These factors are not necessarily the same for each individual. These factors contribute either directly or indirectly to decreased levels or ineffectiveness of an enzyme known as uroporphyrinogen decarboxylase (UROD) within the liver. When UROD levels in the liver decrease to approximately 20% of normal levels, the symptoms of PCT may develop.

PCT is a rare disorder that affects males and females. The disorder usually develops after the age of 30 and its onset in childhood is rare. PCT is found worldwide and in individuals of all races. The prevalence is estimated to be approximately 1 in 10,000 to 25,000 individuals in the general population. PCT is the most common form of porphyria.

Symptoms of the following disorders can be similar to those of PCT. Comparisons may be useful for a differential diagnosis.

A diagnosis of PCT is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests.


Porphyrias

先天性红细胞生成性卟啉病

Porphyria occurs when there is an alteration of one of the enzymes used to make the molecule heme. At least eight different enzymes are involved in making heme. A different gene is responsible for making each of these enzymes. Each type of porphyria is related to a different altered (mutated) gene responsible for one of the enzymes involved in the steps making the molecule heme. Most mutations cause decreased function of the affected enzyme, but mutations in one type of porphyria (XLP) cause an increase in enzyme activity.

The exact number of people who have porphyria is unknown, but it has been estimated that about 1 in 20,000 people may have some type of porphyria. Some forms of porphyria are more common in specific populations. For example, acute intermittent porphyria is more common in Sweden than other parts of the world. Porphyria cutanea tarda may be the most common type of porphyria, occurring in 1 in 25,000 people in the United States. Erythropoietic porphyria is the most common in children, with the highest incidence in the Netherlands of about 1 in 75,000.

Symptoms of the following disorders can be similar to those of the porphyrias. Comparisons may be useful for a differential diagnosis.

Porphyria is diagnosed based on a clinical exam and symptoms, as well as blood, urine and stool tests. Molecular genetic (DNA) testing may be used to help confirm the diagnosis. Once someone in a family has been diagnosed with porphyria, other family members may be tested to see if they have inherited the condition.


Post Polio Syndrome

Post-polio syndrome (PPS) is a syndrome that affects some people who have had polio (poliomyelitis) and occurs many years (typically from 10 to 40 years) after recovery from the initial infection. It is characterized by the development of progressive weakness in muscles that were affected by the original polio infection. In addition, those affected may experience extreme fatigue and joint pain. Skeletal deformities, such as scoliosis, may occur as a result of this syndrome. There is variation in the severity of symptoms. In severe cases, symptoms may mimic those of the rare disorder known as Lou Gehrig’s disease (amyotrophic lateral sclerosis). The degree of muscle atrophy during the post-polio period appears to reflect the severity of the impact of the initial polio infection. People who were significantly affected by polio are more likely to experience severe symptoms from post-polio syndrome. The cause of this syndrome is not known. Although exact numbers are not available, it has been estimated that there are 300,000 polio survivors in the United States and that from one-fourth to one-half of them may ultimately develop some degree of post-polio syndrome.

Post-polio syndrome occurs at least 10 years after a person has been stricken by polio.  It is characterized by gradual deterioration of muscle function and increased weakness that usually occurs in the limbs that were most severely affected by polio.  Sometimes, the disorder involves muscles that appeared to be fully recovered or that were not involved in the original polio attack, including muscles necessary for respiration.  Other symptoms may include fatigue, muscle pain and twitching (fasciculations).

The cause of post-polio syndrome is not known at this time.  One theory is that it may be related to the recovery from the original polio.  During recovery from polio, nerve cells in affected muscles may regrow many smaller branches (dendrites) from the message-transmitting large branches (axons) of nerve cells.  These sprouts take over the function of neurons killed by the polio virus.  It is thought that, after years of functioning beyond capacity, the nerve cells weaken and lose their ability to maintain these tiny dendrites, which then begin to shrink, and the whole muscle becomes weaker.  Additional research is needed to determine whether this may, in fact, be the cause of post-polio syndrome.

Post-polio syndrome affects people who have had acute episodes of poliomyelitis.  It occurs 10 years or more after the original illness, and can occur as long as 40 years afterward.  According to one estimate, 25% to 50% of the 300,000 polio survivors in the United States may develop the syndrome.  At the present time, there is no known way to prevent the syndrome.

Symptoms of the following disorders can be similar to those of post-polio syndrome.  Comparisons may be useful for differential diagnosis:

Amyotrophic lateral sclerosis (ALS) is one of a group of disorders known as motor neuron diseases.  It is characterized by the progressive degeneration and eventual death of nerve cells (motor neurons) in the brain, brainstem and spinal cord that facilitate communication between the nervous system and voluntary muscles of the body.  Ordinarily, motor neurons in the brain (upper motor neurons) sent messages to motor neurons in the spinal cord (lower motor neurons), and then to various muscles.  ALS affects both the upper and lower motor neurons, so that the transmission of messages is interrupted, and muscles gradually weaken and waste away.  As a result, the ability to initiate and control voluntary movement is lost.  Ultimately, ALS leads to respiratory failure because affected individuals lose the ability to control muscles in the chest and diaphragm.  ALS is often called Lou Gehrig’s disease. (For more information on this disorder, choose amyotrophic lateral sclerosis as your search term in the Rare Disease Database.)


Post-transplant lymphoproliferative disease (PTLD) is a rare, but well-known complication of solid organ transplants and hematopoietic stem cell transplantation. PTLD is related to the Epstein-Barr virus and immunosuppression therapy. People who receive these transplants are treated with drugs that suppress the activity of the immune system. Doctors must suppress the immune system to help the body accept the transplant and avoid rejection. Individuals receive these drugs at the time of the transplant (induction therapy) and must remain on these drugs for the rest of their lives (maintenance therapy). Immunosuppressive therapy leaves patients at a greater risk of developing infections and, in some people, of developing post-transplant lymphoproliferative disease. Early diagnosis and prompt treatment of these disorders are extremely important.

The specific symptoms and severity of PTLD can vary greatly from one person to another. Some affected individuals develop a mild, noncancerous overgrowth of affected tissue, while other people can develop a cancerous, life-threatening form of lymphoma. The mild, benign form of PTLD can resemble reactive hyperplasia, the normal process in which lymph nodes become enlarged in response to an infection or inflammation. PTLD can be localized, which means the disease only affects a specific area of the body, or widespread (disseminated), which means it affects several different areas of the body. They can also cause severe, life-threatening complications. In addition, PTLD may affect the transplanted organ, and these disorders commonly involve extranodal tissue.

Post-transplant lymphoproliferative disease may be associated with infection with the Epstein-Barr virus (EBV). This is a common virus that, generally, does not cause any problems in people after an active phase. This virus infects B-cells. After the active phase, the virus remains in the body, where it lies dormant or silent in these cells (latent phase). Most people are first infected with the Epstein-Barr virus in childhood and only develop mild symptoms or no symptoms. If infection first occurs in the teen-aged years or adulthood, affected individuals may develop fever, sore throat, and enlarged lymph nodes. The Epstein-Barr virus is one of the most common causes of infectious mononucleosis or mono. As many as 90-95% of people will be infected with the Epstein-Barr virus at some point during their lives. EBV negative recipients are at higher risk of PTLD.

The incidence and prevalence of post-transplant lymphoproliferative disease varies based on the type of transplant and affects about 1%-2% of people who have received a kidney (renal) transplant. Rates are higher in heart and lung transplants. PTLD occurs most often with gastrointestinal and multiorgan transplants. PTLD is the most common cancer affecting people who receive solid organ transplants after squamous cell carcinoma of the skin. In a retrospective multicenter study, the overall incidence of PTLD in people who had hematopoietic stem-cell transplants was reported to be 3.2%

Symptoms of the following disorders can be similar to those of post-transplant lymphoproliferative disease. Comparisons may be useful for a differential diagnosis.

A diagnosis of a post-transplant lymphoproliferative disease is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests, including a complete blood count (CBC), chemical panel, specialized imaging (x-ray) techniques, an evaluation for the Epstein-Barr virus, and a tissue biopsy.


Posterior urethral valve

Most cases of posterior urethral valves are found before birth during an ultrasound. Doctors look for things like swelling in the tubes that carry urine from the kidneys to the bladder (the ureters) and for a swollen thick-walled bladder that may not empty well. A low level of fluid around the baby or swelling in the baby’s belly may also be seen.

Posterior urethral valves form when a baby is still developing inside its mother, but the cause is not known. Some theories suggest it’s due to problems with the formation of the urinary system. More research is needed to pinpoint the exact cause.

PUV is rare, occurring in about 1 in 5,000 to 1 in 8,000 male infants. It is the most common cause of urinary tract obstruction in newborn males, occurring in roughly 500 babies per year in the U.S.

The following disorders sometimes occur along with PUV:

Posterior urethral valves are typically suspected during prenatal ultrasound and diagnosed with imaging after birth. Doctors look for signs like a swollen bladder, but it’s not always clear. If undetected during pregnancy, symptoms such as difficulty urinating, urinary retention and/or urinary tract infections in infants and young children may raise suspicion.


Posterior uveitis

Uveitis is a general term that refers to inflammation of the part of the eye known as the uvea. The uvea is a relatively thick, strong layer of fibrous tissue that encloses and protects the eyeball. It contains many blood vessels and can cause inflammation in neighboring structures of the eye such as the retina, vitreous, optic nerve head and retinal vessels. The uvea consists of three parts: the iris, ciliary body and choroid.

Some people do not experience symptoms; however, some who experience them may have a sudden onset and get worse quickly.

Uveitis can be caused by a person’s immune system, infections, tumors, bruising, eye injury or exposure to toxins. Posterior uveitis is inflammation of the uvea due to the body’s response to various factors such as microorganisms, toxins and damaged tissue. Inflammation may cause redness, swelling and heat in a particular area of the eye. This reaction can trigger an immune response and lead to the destruction of certain tissues and cause white blood cells to collect in that area of the eye.

Posterior uveitis occurs as an isolated condition or as part of other diseases that affect multiple body systems. This condition affects males and females in equal numbers. It can strike at almost any age, but usually begins between the ages of 30 and 40. According to one estimate, posterior uveitis occurs in 18/100,000 people (2020).

Symptoms of the following disorders can be similar to those of posterior uveitis. Comparisons may be useful for a differential diagnosis:

Anterior uveitis is characterized by inflammation of the front (anterior) part of the eye. It is more common than posterior uveitis and its symptoms, which frequently include pain and redness of the eye, are not as subtle as those of posterior uveitis.


Potter Syndrome

The signs and symptoms of Potter syndrome can vary from one newborn to another. However, the condition is associated with severe complications affecting the developing fetus and is often fatal at or shortly after birth. When caused by bilateral agenesis of the kidneys, Potter syndrome is not compatible with life. Potter syndrome due to other causes is also often fatal at or shortly after birth, but there is an increased chance for survival. Infants who do survive the newborn period generally experience chronic lung disease and chronic kidney failure.

The most common underlying cause of Potter syndrome is absence, underdevelopment or malformation of the kidneys. Absence of both kidneys (bilateral renal agenesis) is the most common condition associated with Potter syndrome. The kidneys produce urine, which makes up the major part of the amniotic fluid, which supports, cushions and protects a developing fetus. Because there is not enough amniotic fluid to protect the fetus, the pressure a fetus undergoes while developing within the uterus that normally does not cause any problems can cause a variety of physical features including distinctive facial features, skeletal abnormalities, and other complications.

Potter syndrome is a rare disorder, and the exact incidence or prevalence is unknown. The main cause of this condition, bilateral renal agenesis, occurs in approximately 1 in 5,000 fetuses and accounts for about 20% of Potter syndrome cases. The incidence or prevalence of other causes are unknown. Overall, estimates for the incidence or prevalence of Potter syndrome range from 1 in 4,000 to 10,000 births. A couple studies have shown that male newborns are affected more often than female newborns, probably due to the obstructive uropathy that is seen more often in males.

A diagnosis of Potter syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and certain specialized tests. If not detected before birth (prenatally), then lack of urine production, specific (facial) features or difficulty breathing may be signs of Potter syndrome.

There is no treatment for Potter syndrome due to bilateral absence of the kidneys, which is not compatible with life. Efforts should be made to ensure the entire family receives coping support and grief counseling. Genetic counseling is recommended. Psychosocial support for the entire family is essential as well.


Prader-Willi syndrome

The symptoms and severity of PWS can vary from one person to another. Many features of the disorder are nonspecific, and others may develop slowly over time or can be subtle. It is important to note that affected individuals may not have all the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. Often this requires input from a clinical geneticist or genetic counselor with experience in this genetic disorder to supply the most recent and accurate information about the disorder and discuss genetic testing options or treatment plans.

PWS occurs when the genes in a specific region of chromosome 15 are not present or do not function. This region of chromosome 15 is located at 15q11.2-q13 and has been designated the Prader-Will syndrome/Angelman syndrome region (PWS/AS). In individuals with PWS, the nonfunctioning PWS/AS region is always located on the number 15 chromosome inherited from the father.

PWS affects males and females in equal numbers and occurs in all ethnic groups and geographic regions in the world. Most estimates place the incidence between 1 in 10,000-30,000 individuals in the general population and about 350,000-400,000 individuals worldwide.

Symptoms of the following disorders can be similar to those seen in PWS including fragile X, Bardet-Biedl Cohen, Borjesson-Forssman-Lehmann, and Alstrom syndromes, uniparental disomy 14 and several other different chromosomal alterations besides chromosome 15, Albright hereditary osteodystrophy, congenital muscular dystrophy and spinal muscular atrophy. For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.

A diagnosis of PWS is based upon a detailed patient history, thorough clinical evaluation and identification of characteristic symptoms. Consensus diagnostic criteria for PWS have been established and are effective for identifying potential cases of PWS but genetic testing is required to confirm the diagnosis and to identify the specific genetic subtype (15q11-q13 deletion, maternal disomy 15, imprinting defect). Hence, all infants and newborns with unexplained hypotonia and poor suck should be tested for PWS. To confirm a diagnosis of PWS, certain specialized tests are required including DNA methylation tests and fluorescent in situ hybridization (FISH). More recently, high resolution chromosomal microarray studies with several hundred thousand DNA probes (e.g., 2.8 million probes) from throughout the genome representing all chromosomes can be utilized to identify small deletions or duplications of the chromosomes that cannot be seen with routine chromosome studies. High resolution chromosome microarrays are most useful in identifying the typical chromosome 15q11-q13 deletions in which there are two types (larger type I and smaller type II), other rearrangements of this chromosome region, imprinting defects and specific maternal disomy 15 subclasses seen in PWS. Genetic laboratory testing algorithms and advances in genetic technology have allowed more precise testing results and PWS molecular genetic class identified which is important as the severity of clinical findings, disease surveillance and recurrence risks can depend on the specific genetic abnormality.


Precocious Puberty

Precocious puberty means an abnormally early onset of puberty. A sequence of events occurs during which a child develops into a young adult beginning at an unexpectedly early age. Glands that secrete growth and sex hormones begin to function abnormally early in life resulting in this condition. Often, the exact cause of precocious puberty is not known.

Secondary sexual characteristics include testicular enlargement (>3 ml) and/or pubic hair development in boys, and breast and/or pubic hair development in girls. Other signs suggestive of pubertal onset include acne, growth acceleration, voice changes, vaginal discharge or bleeding, and advanced skeletal maturation. There are many terms used to describe pre-pubertal children who have isolated signs of puberty. These children, however, do not necessarily meet the criteria for true precocious puberty. These terms include premature thelarche, premature adrenarche, premature pubarche and premature menarche. The terminology is often confusing as these are also referred to by some authors as incomplete precocious puberty.

Central precocious puberty (CPP) can be caused by CNS tumors (craniopharyngioma, glioma, etc.) and other CNS disorders including: hypothalamic hamartoma of the tuber cinereum, encephalitis, brain abscess, static encephalopathy, global delays, sarcoid or tubercular granuloma, head trauma, vascular lesion, cranial irradiation, or neurofibromatosis type 1 (usually associated with optic glioma). A large proportion of CPP is idiopathic, especially in females; however, research is beginning to identify rare genetic causes for some of these cases. For instance, activating mutations of the kisspeptin gene (KISS1) and its receptor (KISS1R), which are known for their stimulatory effect on the hypothalamus ultimately leading to increased gonadotropin secretion, have been identified as precipitating precocious puberty. Additionally, inactivating mutations of a paternally inherited MKRN3 gene, similar to that seen in Prader-Willi syndrome, has been implicated in early puberty.  CPP can also follow the treatment of virilizing congenital adrenal hyperplasia or the treatment of other causes of gonadotropin independent precocious puberty (GIPP).

This disorder is classically characterized among females by breast development beginning before the age of eight years in white girls, 6.8 years for Hispanic girls and 6.6 years for Black girls, or the onset of menstruation before the age of approximately ten years (white-10.6 years, Hispanic-10.0 years and black-9.7 years). Among males, precocious puberty can be defined as pubertal development beginning before the age of nine years for white males, 9.5 years for Hispanic males and 8 years for black males. Boys with this disorder will usually have testicular and genital enlargement occur first and then tend to exhibit pubic, underarm (axillary) and facial hair, accelerated growth, and a deepening voice. Puberty may occur even before three years of age in some cases of this disorder.

Symptoms of the following disorders can be similar to those of precocious puberty. Comparisons may be useful for a differential diagnosis:

Pseudo-precocious puberty is characterized by high sex steroid levels due either to ingestion of sex steroids, hormone-producing tumors (usually of the ovaries or testes), or abnormalities of the adrenal gland which cause over-production of hormones. Although patients appear to be maturing sexually, ovulation or sperm production may not occur because the gonads are not mature. However, in children with true precocious puberty, ovulation and sperm production can occur abnormally early in life.


Primary biliary cholangitis

Primary biliary cholangitis (PBC) is a chronic (e.g.,long lasting), progressive liver disorder that mostly affects women and usually appears during middle age. Approximately 25% of patients with PBC are women younger than 40 years of age, and about 10% of patients are men. PBC leads to inflammation and scarring of the small bile ducts (the ‘plumbing’ system of the liver which transports bile, the substance that helps digest fat). When PBC is very severe, it can lead to yellow discoloration of the skin (jaundice), which occurs when bilirubin levels rise above 2 to 3mg/dL or 34 to 51 µmol/L). If PBC is untreated or there is incomplete response to medical treatment, it can lead to cirrhosis (e.g., scarring of the entire liver), which can lead to liver failure. PBC is divided into four stages from stage 1 (early disease, without significant scarring of the liver) to stage 4 (cirrhosis). Although the exact cause of PBC is unknown, it is thought that it is likely due to a combination of factors such as autoimmune (when a person’s own immune system attacks their body), genetic, and environmental factors.

The exact cause of PBC is unknown. Possible immunological, autoimmune, genetic, and/or environmental factors are under investigation as potential causes.

PBC affects mostly women, but more men are now being diagnosed. The disorder usually becomes apparent during middle age, initially affecting most individuals between the ages of 45 to 65 years. However, the disorder has been diagnosed in females as young as 22 years of age and in females in their early 90s. It has been estimated that PBC is one of the most common autoimmune diseases, affecting nearly 1 in 1000 women over the age of 40.

Other diseases that may need to be ruled out include the following:

The diagnosis of PBC requires the presence of:

In 2004, the drug ursodiol (Urso), also known as ursodeoxycholic acid (UDCA), was approved by the US Food and Drug Administration (FDA) for the treatment of PBC. Ursodiol is manufactured by Axan Pharma and Schwarz Pharma US.


Primary central nervous system lymphoma

原发性中枢神经系统淋巴瘤

The potential symptoms of primary CNS lymphoma are varied and mostly depend on the location of the tumor. Symptoms typically develop over weeks (subacute).

Primary CNS lymphomas most often develop from the uncontrolled proliferation of cells derived from B lymphocytes (also known as B cells), which are a type of immune cell. More rarely, PCNSL can also develop from T lymphocytes (also known as T cells), but our understanding of prognosis and therapies for PCNSL is based on patients who specifically have primary diffuse large B-cell lymphoma of the CNS. The exact mechanism by which malignant lymphocytes invade the brain is not understood yet, but there are two main hypotheses: lymphocytes might be drawn to the CNS and then replicate and lead to a malignant tumor. Alternatively, already malignant lymphocytes might be drawn to the CNS via the expression of specific adhesion molecules that mediate traffic to the brain.

Primary central nervous system lymphoma constitutes 2-3% of all brain tumors and develops in around five individuals per million each year, for a total of approximately 1,500 new cases per year in the United States. PCNSL is slightly more common in males. The most common risk factor for the development of a primary CNS lymphoma is an impaired immune system (immunosuppression). This is notably the case of patients living with HIV/ AIDS, especially those who are not treated who have a high viral load and low CD4+ cell count. Other immunosuppressed patients include organ transplant recipients and individuals with congenital immunodeficiency syndromes. In fact, primary CNS lymphoma is the most common brain tumor in immunosuppressed patients. The other main risk factor for developing a PCNSL is age. Most immunocompetent patients are diagnosed around age 65, although cases of PCNSL have also been reported in children. AIDS-related PCNSL most often develops during the fifth decade of life (age 40-49). There has been an increase in the incidence of immunocompetent PCNSL, particularly in the elderly.

Symptoms of the following disorders can be similar to those of primary central nervous system lymphoma. Comparisons may be useful for a differential diagnosis:

Other types of brain tumors have symptoms similar to primary CNS lymphoma. They are classified according to their origin. Examples include gliomas, meningiomas, medulloblastomas and brain metastases, which are more common than tumors arising in the brain (primary brain tumors) and come from cancers elsewhere in the body, including the lungs, breasts and gastrointestinal tract.


Primary ciliary dyskinesia

Primary ciliary dyskinesia (PCD) is a genetic condition in which the microscopic organelles (cilia) in the respiratory system do not function properly. Ciliary dysfunction prevents the clearance of mucous from the lungs, paranasal sinuses and middle ears. Bacteria and other irritants in the mucous lead to frequent respiratory infections. Kartagener syndrome is a type of PCD associated with a mirror-image orientation of the heart and other internal organs (situs inversus). PCD usually follows autosomal recessive inheritance, but rare cases of X-linked and autosomal dominant inheritance have been observed.

The severity of symptoms of primary ciliary dyskinesia varies in affected individuals. Symptoms often begin shortly after birth and can include coughing, gagging, choking and neonatal respiratory distress (lung atelectasis). Affected individuals often experience chronic sinus, middle ear and lung infections as well as chronic coughing, excess mucus and hearing loss. The recurring respiratory infections can lead to irreversible scarring and dilatation in the bronchi (bronchiectasis) and severe lung damage.

PCD is known to be caused by changes (disease-causing variants) in over 50 genes. This does not account for all cases of PCD, therefore, more PCD genes are yet to be identified.

Primary ciliary dyskinesia occurs in approximately 1 in 16,000 to 20,000 births. Only half of primary ciliary dyskinesia results in Kartagener syndrome. Recent studies have estimated the overall global prevalence of primary ciliary dyskinesia to be at least 1 in 7,554 individuals.

Symptoms of the following disorders can be similar to those of primary ciliary dyskinesia. Comparisons may be useful for a differential diagnosis:

Cystic fibrosis is a genetic disease that often affects multiple organ systems of the body. Cystic fibrosis is characterized by abnormalities affecting certain glands (exocrine) of the body, especially those that produce mucus. Saliva and sweat glands may also be affected. Exocrine glands secrete substances through ducts, either internally (e.g., glands in the lungs) or externally (e.g., sweat glands). In cystic fibrosis, these secretions become abnormally thick and can clog up vital areas of the body causing inflammation, obstruction and infection. (For more information on this disorder, choose cystic fibrosis as your search term in the Rare Disease Database.)


Primary Craniosynostosis

前脑无裂畸形-颅缝早闭综合征

Primary craniosynostosis is a general term for the improper development of the bones of the skull, which can result in an abnormal head shape in affected individuals. Craniosynostosis refers to the premature fusion of the fibrous joints (sutures) between certain bones of the skull. The severity of primary craniosynostosis can vary from one person to another. While raised intracranial pressure is unlikely with single suture abnormalities with intelligence usually being unaffected, recent data and debate about unrecognized elevated pressure (as well as effects upon cognition) has led to considerable controversy. Until we are able to measure intracranial pressure via non-invasive means, it is likely that the surgical argument between appearance and brain pressure will continue. Primary craniosynostosis may occur as an isolated finding or as part of a syndrome. Patients with syndromic conditions generally have more than one suture involved. Not surprisingly, the therapeutic options and outcomes are dependent upon the degree of suture involvement. The main treatment for primary craniosynostosis is surgery, but not all affected children will require surgery. The exact cause of primary craniosynostosis is unknown, although the skull abnormalities may result from the abnormal hardening (ossification) of the cranial sutures. Primary craniosynostosis is distinguished from secondary craniosynostosis, which occurs because of a primary failure in brain growth which in turn may lead to abnormalities in head shape, occasionally mimicking craniosynostosis.

Primary craniosynostosis is usually apparent at birth or within a few months shortly thereafter (neonatal period). Mild cases may go undiagnosed until early during childhood.

The exact cause of primary (isolated) craniosynostosis is unknown. Primary isolated craniosynostosis refers to cases that are not associated with a larger syndrome. Most cases occur randomly for no apparent reason (sporadically) although an infant’s position in utero, large size and presence of twins have all been implicated as etiological factors. A variety of different genetic and environmental factors are suspected to play a role in the development of primary isolated craniosynostosis.

Primary craniosynostosis affects individuals of all races and ethnicities and is usually present at birth. Most forms of primary craniosynostosis affect men and women in equal numbers (although males outnumber females 2:1 for sagittal synostosis). Primary craniosynostosis affects approximately 0.6 in 100,000 people in the general population. Overall, craniosynostosis affects approximately 1 in 2,000-2,500 people in the general population. Approximately 80-90 percent of individuals with primary craniosynostosis have isolated defects. The remaining cases of primary craniosynostosis occur as part of a larger syndrome. More than 150 different syndromes have been identified that are potentially associated with craniosynostosis.

Symptoms of the following disorders can be similar to those of primary craniosynostosis. Comparisons may be useful for a differential diagnosis.

A diagnosis of primary craniosynostosis is made based upon identification of characteristic symptoms, a detailed patient history, and a thorough clinical evaluation that includes careful assessment of the shape of the skull. A variety of specialized tests include specialized imaging techniques. Such imaging techniques may include computerized tomography (CT) scanning and magnetic resonance imaging (MRI), although a head CT is best for evaluating suture / bone involvement. Although there has been recent debate about the need for CT’s prior to surgery (and accompanying radiation), there are a number of literature reports documenting their value in ruling out other suture involvement as well as brain abnormalities. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of certain tissue structures. Routine skull x-rays have been discontinued as a routine diagnostic tool in the setting of craniosynostosis due to the lack of sensitivity and frequent inaccuracy.


Distal renal tubular acidosis

Primary distal renal tubular acidosis is a highly variable disorder; this means that the disorder affects people differently. Some individuals may only have slightly elevated acid levels and no accompanying symptoms (asymptomatic). Some individuals living with primary dRTA may experience kidney stones and others may not. Generally, people with an autosomal dominant pattern of inheritance have milder symptoms and a later age of onset of symptoms than people with an autosomal recessive pattern of inheritance. However, this is not always true and sometimes more severe complications such as growth failure or rickets (bowing of the bones) can affect individuals with dominantly-inherited primary distal renal tubular acidosis.

Primary distal renal tubular acidosis is caused by a variation (mutation) in one of at least three different genes, the SLC4A1 gene, the ATP6V0A4 gene, and the ATP6V1B1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, absent, or overproduced. Depending upon the functions of the particular protein, this can affect many organ systems of the body. In some affected individuals, no variation in these three genes can be identified suggesting that other, as-yet-unidentified genes can play a role in primary dRTA.

Primary distal renal tubular acidosis affects females and males in equal numbers. The exact number of people who have this disorder is unknown. Rare disorders like primary distal renal tubular acidosis often go misdiagnosed or undiagnosed, making it difficult to determine their true frequency in the general population.

Symptoms of the following disorders can be similar to those of primary distal renal tubular acidosis. Comparisons may be useful for a differential diagnosis.

A diagnosis of primary distal renal tubular acidosis is based upon identification of characteristic symptoms, a detailed patient and family history, a thorough clinical evaluation and a variety of specialized tests. The disorder may be suspected in individuals with unexplained metabolic acidosis and an elevated plasma chloride (so called normal anion gap metabolic acidosis).


双侧纹状体-苍白球-齿状核钙化

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by the presence of abnormal calcium/hydroxyapatite deposits (calcifications) in the brain. The clinical presentations generally attributed to these brain calcifications are highly heterogeneous, ranging from asymptomatic patients to severe cases with progressive neuropsychiatric features. To date, disease-causing changes (pathogenic variants or mutations) in six genes have been associated with PFBC: SLC20A2, PDGFB, PDGFRB, XPR1, MYORG and JAM-2.  PFBC has recently become the preferred name for this condition because variants in specific genes are now known to be the cause of the condition. Previously, familial idiopathic basal ganglia calcification was the preferred name, and Fahr’s disease is often used for either familial or sporadic brain calcification, and it is unknown if these are the same or different diseases.

PFBC is characterized by symmetric and bilateral brain calcifications mainly in the basal ganglia, but also seen in the cerebellum, thalami, cerebral white matter and/or pons. These calcium phosphate deposits are commonly found in the fourth to fifth decade of life, while symptoms usually begin in the third to fifth decade of life, even though some individuals with PFBC may be clinically asymptomatic for several decades. PFBC is rare among children but, when present, most of these children present with seizures. Neuropsychiatric and movement disorders are the main PFBC clinical presentations in adults.

PFBC is caused by variants in several different genes, and it can either be inherited or develop spontaneously. In inherited cases, the vast majority follow autosomal dominant inheritance, but autosomal recessive inheritance have also been reported.

The prevalence of PFBC is unknown, but more people are being diagnosed, probably due to the growing availability of neuroimaging screening and genetic testing.

Calcification of the basal nuclei in the brain is found in many medical conditions and can be caused by infections as well as metabolic and other genetic syndromes. It is also not uncommon to observe calcium deposits of the basal ganglia in individuals over 60 years of age and this finding is not usually associated with diseases. Symptoms of the following disorders may be similar to those of PFBC. Comparisons may be useful for a differential diagnosis:

Parkinson disease is a slowly progressive neurologic condition characterized by involuntary trembling (tremor), muscular stiffness or inflexibility (rigidity), slowness of movement and difficulty carrying out voluntary movements. Degenerative changes occur in areas deep within the brain (substantia nigra and other pigmented regions of the brain), causing a decrease in dopamine levels in the brain. Dopamine is a neurotransmitter, which is a chemical that sends a signal in the brain.

To date, no specific treatment for PFBC is known. Medications can be used to treat symptoms associated with this condition, such as movement disorders, seizures, anxiety, headaches, depression, psychosis and urinary incontinence (Oliveira JRM, 2011). Medications established in psychiatric clinical practice are generally prescribed to control other disorders, such as mood stabilizers (mainly anticonvulsants) that may be useful in managing depressive symptoms, irritability, euphoria or agitation. Antipsychotics are also used to treat symptoms such as delusions and hallucinations, but they are also useful for managing psychomotor agitation.


Primary Gastric Lymphoma

The symptoms of primary gastric lymphoma are usually vague and nonspecific, seen in other conditions beside cancer. In many people, there may be no noticeable physical findings upon diagnosis. Specific symptoms can be very different from one person to another. Abdominal pain or cramping is probably the most common and may be one of the first symptoms noted.

The exact cause of primary gastric lymphoma is unknown. However, a strong association between infection with Helicobacter pylori (H. pylori) and the development of MALT gastric lymphoma has been established. H. pylori is a bacterium that is found in the stomach and the upper portion of the intestines and is well known for causing ulcers.

Primary gastric lymphoma is estimated to affect approximately 1 in 100,000 people in the general population in Western countries. Several reports have noted that the incidence is increasing. Most cases of primary gastric lymphoma occur in individuals 50 years or older, with a peak incidence in the 60s and 70s. However, cases have been reported in children, adolescents and young adults. Some reports suggest that males are affected more often than females. Primary gastric lymphoma has also been reported to occur more frequently in Caucasians than African Americans.

The following disorders can have symptoms similar to primary gastric lymphoma.

Primary gastric lymphoma is diagnosed based upon a thorough clinical evaluation, detection of certain symptoms and physical findings, a detailed patient history and a variety of specialized tests. Such testing is necessary to confirm the specific type (and subtype) of NHL present, to assess the nature and extent of the disease and to determine the most appropriate treatments.


Primary Hyperoxaluria

PH has characteristic or core symptoms, but some aspects of these disorders are still not fully understood. Several factors including the small number of identified cases (especially with PH types II and III), the lack of large clinical studies, and multiple genes influencing the disorders prevent physicians from developing a complete picture of associated symptoms and prognosis. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.

PH type I is caused by changes (mutations) in the AGXT gene. PH type II is caused by mutations in the GRHPR gene. PH type III is caused by mutations in the HOGA1 gene. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.

PH affects males and females in equal numbers. The exact incidence and prevalence of these disorders is unknown. Because some cases go undiagnosed or misdiagnosed, determining the true frequency of these conditions in the general population is difficult. Molecular genetic testing of young patients with recurring kidney stone formation can aid in diagnosis. However, some patients with common symptoms of PH are not found to have the known genetic mutations linked to PH, which likely underestimates the true number of people with PH. PH type I is the most common form. One estimate places the prevalence of PH type I at 1-3 cases per 1,000,000 people in the general population with fewer than 1,000 individuals with PH in the United States and the incidence at 1 case per 120,000 live births per year in Europe. PH is thought to be approximately 2.5 times more common in European Americans than African Americans.

Symptoms of the following disorders can be similar to those of PH. Comparisons may be useful for a differential diagnosis.

A diagnosis of PH is based upon identification of characteristic symptoms (e.g. chronic stone formation), a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. Children with nephrocalcinosis or kidney stones should be screened for PH. PH may be suspected in individuals with a history of recurrent kidney stones and/or nephrocalcinosis. Because these conditions are rare, there may a delay from symptom onset to diagnosis.


Primary Hyperparathyroidism

家族性原发性甲状旁腺功能亢进症

Primary hyperparathyroidism is a condition in which the parathyroid glands produce too much parathyroid hormone and the calcium level in the blood becomes elevated. The parathyroid glands are part of the endocrine system, the network of glands that secrete hormones into the bloodstream where they travel to various areas of the body. Endocrine glands release hormones that regulate the chemical processes (metabolism) that influence the function of various organs and activities within the body. Hormones are involved in numerous vital processes including regulating heart rate, body temperature and blood pressure, as well as cell differentiation and growth, and in modulation of several metabolic processes. There are four tiny parathyroid glands found in the neck. They are about the size of a pea. Parathyroid hormone (along with vitamin D) is the main regulator of the level of calcium in the blood. It also affects the blood phosphorus level, bone growth and bone cell activity. Most individuals with primary hyperparathyroidism do not develop symptoms (asymptomatic) or have only extremely mild symptoms. Primary hyperparathyroidism mainly affects the skeleton and the kidneys, but the heart, gastrointestinal, and nervous system can sometimes be involved. About 80-85% of the time, the disorder is caused by a benign tumor called an adenoma that is usually found in one of the four parathyroid glands.

The most common cause of primary hyperparathyroidism is a tiny, benign tumor called an adenoma. Usually, one adenoma forms in one of the four parathyroid glands, but it is possible for more adenomas to form in multiple parathyroid glands. An adenoma causes the affected gland to become overactive. Multiple gland hyperplasia accounts for about 6-12%. This condition is characterized by enlargement of multiple parathyroid glands because of an increased reproduction rate of their cells. Multiple gland hyperplasia occurs randomly (sporadically) or as part of a larger genetic syndrome. Double adenomas account for about 2-5%.

Estimates of the incidence and prevalence of primary hyperparathyroidism in the Western world vary. Most people with the disorder, more than 80% in the Western world, do not have any symptoms (asymptomatic). Individuals with symptoms, particularly severe symptoms, are a rarer occurrence in developed countries where routine screening of calcium is common. Primary hyperparathyroidism can occur at any age but is most likely to affect individuals over 50. The incidence is highest among individuals of African American heritage, followed by Caucasians. Women are affected about three times more often than men. According to one estimate, about 100,000 people in the United States develop primary hyperparathyroidism each year.

Some characteristics or symptoms of the following disorders can be similar to those of primary hyperparathyroidism. Comparisons may be useful for a differential diagnosis.

A diagnosis of primary hyperparathyroidism is based primarily upon blood and urine tests. A thorough clinical evaluation that assesses symptoms and family history as well as a variety of specialized tests is also performed to determine the cause, effects on the skeleton and kidney and the need for surgery. Individuals with kidney stones may be suspected of having primary hyperparathyroidism.


Primary intestinal lymphangiectasia

Primary intestinal lymphangiectasia (PIL) is a rare digestive disorder characterized by abnormally enlarged (dilatated) lymph vessels supplying the lining of the small intestine. The main symptoms are swelling (edema) of the limbs and abdominal discomfort. The disorder is usually diagnosed before three years of age but is sometimes diagnosed later in life.

The most obvious sign of the disorder is moderate to severe swelling in the lower limbs, eventually face, abdomen and external genitalia due to fluid retention (edema). Fluid is retained because the blood protein (albumin) levels are low. Lymphedema may also be associated and not easy to differentiate from edema.

The cause of PIL is unknown. Multiple affected family members have been reported rarely.

PIL is a rare disease that affects males and females in equal numbers. The prevalence is unknown.

The diagnosis of PIL is made by viewing the intestine with a flexible scope (endoscope), removing tissue samples from several areas (biopsy) and examining these tissues for signs of abnormal dilation. This exam is rarely normal and videocapsule endoscopy may be useful when endoscopic findings are not contributive. Intestinal lymph oozing may be confirmed by the increased clearance of alpha-1 antitrypsin in the stools.


Primary lateral sclerosis

Primary lateral sclerosis (PLS) is a rare, neuromuscular disorder that affects the central motor neurons and is characterized by progressive weakness and stiffness of the muscles of the legs. Such weakness may progress to affect the arms and the muscles at the base of the brain (bulbar muscles). Less frequently, the muscles of the face are affected. In most cases, the disorder affects adults during midlife. The exact cause of primary lateral sclerosis is unknown.

Primary lateral sclerosis is a rare disorder affecting the nerve cells that control voluntary muscles. In most cases, the muscles of the legs are involved first. However, in some cases, the disorder may begin in the muscles of the hands or tongue.

The exact cause of primary lateral sclerosis is not known. Most cases seem to occur randomly, for no apparent reason (sporadically). Primary lateral sclerosis is one of a group of disorders known as motor neuron diseases. Motor neuron diseases are characterized by malfunction of the nerve cells (motor neurons) within the brain and spinal cord that carry instructions from the brain to the muscles.

Primary lateral sclerosis is a rare disorder that affects males and females in equal numbers. In most cases, the disorder occurs during the fifth decade. However, according to the medical literature a familial form may exist that affects children. The exact prevalence of primary lateral sclerosis and motor neuron diseases is unknown.

Symptoms of the following disorders can be similar to those of primary lateral sclerosis. Comparisons may be useful for a differential diagnosis:

Amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease) is a disorder that affects the motor neuron cells. It generally affects both the upper and lower motor neurons and results in the progressive wasting and weakening of those muscles that have lost their nerve supply. A number of different forms of ALS exist, all exhibiting some of the classic symptoms. The early symptoms of ALS include slight muscle weakness, clumsy hand movements, and/or difficulty performing tasks that require delicate movements of the fingers and/or hands. Muscular weakness in the legs may cause tripping and falling. People with ALS may have difficulty swallowing (dysphagia), and speech may be slowed. The exact cause of amyotrophic lateral sclerosis is unknown. (For more information on this disorder, choose ALS as your search term in the Rare Disease Database.)

Treatment of primary lateral sclerosis involves the use of drugs to help control specific symptoms. Baclofen and tizanidine may be prescribed for spasticity, quinine for cramps, and diazepam, a drug that relaxes muscles, for muscular contractions. Additional treatments may include physical therapy to prevent stiffness of joints, and speech therapy may be needed to aid affected individuals whose ability to speak has been impaired by muscle weakness. Other treatment is symptomatic and supportive.