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ERROR: type should be string, got "https://profreg.medscape.com/px/getpracticeprofile.do?method=getProfessionalProfile&urlCache=aHR0cHM6Ly9lbWVkaWNpbmUubWVkc2NhcGUuY29tL2FydGljbGUvOTU3MTg2LW92ZXJ2aWV3\nDrugs & Diseases > Pediatrics: General Medicine\nUpdated: Feb 01, 2019\nAuthor: Zora R Rogers, MD; Chief Editor: Hassan M Yaish, MD more...\nSections Pearson Syndrome\nLaboratory Studies\nImaging Studies\nHistologic Findings\nPearson marrow-pancreas syndrome, an often fatal disorder, was first described in 1979, by pediatric hematologist/oncologist Howard Pearson. Affected infants manifest a refractory, transfusion-dependent sideroblastic anemia, vacuolization of hematopoietic precursors, and exocrine pancreatic insufficiency. [1] The last, although frequently encountered, may be absent in some cases of Pearson syndrome. The condition is now known to be a rare, multisystemic, mitochondrial cytopathy with anemia, neutropenia, and thrombocytopenia, as well as variable hepatic, renal, and endocrine failure. Death usually occurs early in life (before age 4 years). The most common causes of death are lactic acidemia (which may be triggered by infection) and liver or renal failure. [2] Survivors after early childhood develop features of Kearns-Sayre syndrome (KSS), a mitochondriopathy characterized by progressive external ophthalmoplegia, weakness of skeletal muscle, atypical retinal pigmentation, and cardiac conduction defects.\nThe syndrome is due to mitochondrial DNA (mtDNA) deletions of variable size and location; mtDNA encodes for 13 of the respiratory chain enzymes, along with 24 RNA molecules used in intramitrochondrial protein synthesis. As a result, defective oxidative phosphorylation, as well as other defects (occurring in enzymes and RNA molecules), is involved in the syndrome's etiology. Patients may recover from the refractory anemia.\nMitochondriopathies\nThe mitochondriopathies comprise several diverse, overlapping syndromes caused by mutations of mitochondrial DNA. [3] Pearson syndrome is a specific clinical subset of these syndromes in which involvement of the bone marrow and exocrine pancreas is prominent. The pathogenesis of Pearson syndrome is complex and not well understood. Deletions of certain components of the electron transport chain, encoded by mitochondrial DNA, cause a defect in cellular oxidative metabolism. Certain transfer RNAs (tRNAs) may also be deleted, and their deletion impairs the translation of messenger RNAs (mRNAs) to proteins.\nThe specific mtDNA deletion includes deletion of the complete genes for ATPases 6 and 8, cytochrome c oxydase III, and NADH dehydrogenase 3, 4, 4L, and 5. [4, 5, 6, 7]\nThese defects cause cellular injury in target tissues.\nOther mitochondriopathies, such as KSS and the mitochondrial myopathies, have deletions of mitochondrial DNA that may be similar or identical to those detected in Pearson syndrome. How similar abnormalities of mitochondrial DNA cause such diverse disorders is not well understood. The distinct phenotypes are probably the result of differences in the amount and in the tissue-specific distribution of abnormal mitochondrial DNA, the evolution of this distribution over time, and the effects of tissue-specific nuclear modifier genes. [8, 9]\nDefining features of Pearson syndrome\nThe first defining feature of Pearson syndrome is marrow failure. Sideroblastic anemia, usually macrocytic and frequently transfusion dependent, is observed in isolation or associated with neutropenia and thrombocytopenia. Bone marrow examination is hypoplastic with characteristic vacuolation of hematopoietic precursors and ringed sideroblasts (see the images below).\nCharacteristic vacuolization of a hematopoietic precursor in the bone marrow. (Light microscopy; 100x; Wright-Giemsa stain)\nView Media Gallery\nElectron photomicrograph of a hematopoietic precursor (normoblast) with vacuolization. (Transmission electron microscopy; original 10,000x)\nThe second defining feature of Pearson syndrome is dysfunction of the exocrine pancreas due to fibrosis and acinar atrophy. The result is malabsorption, chronic diarrhea, and poor growth or failure to thrive. Studies have reported that 23-63% of patients with Pearson syndrome do not suffer from pancreatic insufficiency. In a retrospective cohort study by the Marrow Failure Study Group of the Associazione Italiana Emato-Oncologia Pediatrica (AIEOP), the investigators found no such insufficiency in 73% of patients. [10]\nAnother cardinal feature of Pearson syndrome is persistent or intermittent lactic acidemia, which is caused by defects in oxidative phosphorylation. Increased lactate/pyruvate ratio is observed along with increased urinary excretion of lactate and related organic acids.\nOther organ systems are affected in various ways. Hepatic involvement may cause increases in transaminase, bilirubin, and lipid levels, as well as in steatosis. Some patients develop hepatic failure. Renal involvement is common and manifests as a tubulopathy, such as Fanconi syndrome. Endocrinologic disturbances, such as growth hormone deficiency, hypothyroidism, and hypoparathyroidism, may develop but are not usually part of the initial presentation. [11] The endocrine pancreas usually remains functional; however, a few patients develop diabetes mellitus and adrenal insufficiency. Splenic atrophy and impaired cardiac function have also been reported. [12, 13, 14, 15, 16]\nFailure to thrive is common. Several factors are likely contributory. Such factors include a defect in cellular metabolic energy, malabsorption due to exocrine pancreatic failure, hepatic and renal insufficiency, abnormal myelinization, and possibly endocrinologic abnormalities. [17, 18]\nPearson syndrome is rare. Less than 100 cases have been reported worldwide.\nSee United States.\nMortality/Morbidity\nPearson syndrome is often fatal in infancy or early childhood. The usual causes of death are bacterial sepsis due to neutropenia, metabolic crisis, and hepatic failure.\nAll races can be affected.\nPearson syndrome has no sex predilection.\nPearson syndrome is a progressive disease, and its features change with age. Neonates may be well at birth, but some 40% of patients present in the first year with persistent hypoplastic anemia, other cytopenias, low birth weight, microcephaly, and multiple organ system involvement (GI, neuromuscular, and metabolic). [17, 19, 20] Hydrops fetalis has also been reported. Anemic newborns may need transfusion.\nDuring infancy and early childhood, failure to thrive, chronic diarrhea, and progressive hepatomegaly often occur in individuals with Pearson syndrome. These conditions are punctuated by episodic crises characterized by somnolence, vomiting, electrolytic abnormalities, lactic acidosis (elevated lactate:pyruvate ratio), and hepatic insufficiency. The lactic acidosis may become persistent with time. Typical causes of death in infants and young children with Pearson syndrome are metabolic crisis, hepatic failure, and overwhelming sepsis related to neutropenia.\nSome patients survive infancy and early childhood and spontaneously recover from the hematologic dysfunction. Case reports document a shift in the phenotype of these individuals to a predominantly myopathic or encephalopathic condition. For example, some patients who survive early childhood may develop KSS or Leigh syndrome, whereas others may be neurologically healthy. In the aforementioned AIEOP study, the investigators reported that, while all of the 11 patients in the study tested neurologically normal at birth, seven of them (64%) subsequently suffered from retardation of speech development, hypotonia, and muscle hypotrophy, with three patients eventually approaching a complete KSS phenotype. [10]\nPearson HA, Lobel JS, Kocoshis SA, et al. A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction. J Pediatr. 1979 Dec. 95(6):976-84. [Medline].\nBlaw ME, Mize CE. Juvenile Pearson syndrome. J Child Neurol. 1990 Jul. 5(3):187-90. [Medline].\nHerst PM, Rowe MR, Carson GM, Berridge MV. Functional Mitochondria in Health and Disease. Front Endocrinol (Lausanne). 2017. 8:296. [Medline]. [Full Text].\nRotig A, Bourgeron T, Chretien D, et al. Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome. Hum Mol Genet. 1995 Aug. 4(8):1327-30. [Medline].\nRotig A, Cormier V, Koll F, et al. Site-specific deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. Genomics. 1991 Jun. 10(2):502-4. [Medline].\nRotig A, Cormier V, Blanche S, et al. Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest. 1990 Nov. 86(5):1601-8. [Medline].\nKerr DS. Protean manifestations of mitochondrial diseases: a minireview. J Pediatr Hematol Oncol. 1997 Jul-Aug. 19(4):279-86. [Medline].\nDe Vivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Dev. 1993 Jan-Feb. 15(1):1-22. [Medline].\nHarding AE, Hammans SR. Deletions of the mitochondrial genome. J Inherit Metab Dis. 1992. 15(4):480-6. [Medline].\nFarruggia P, Di Cataldo A, Pinto RM, et al. Pearson Syndrome: A Retrospective Cohort Study from the Marrow Failure Study Group of A.I.E.O.P. (Associazione Italiana Emato-Oncologia Pediatrica). JIMD Rep. 2016. 26:37-43. [Medline]. [Full Text].\nWilliams TB, Daniels M, Puthenveetil G, Chang R, Wang RY, Abdenur JE. Pearson syndrome: unique endocrine manifestations including neonatal diabetes and adrenal insufficiency. Mol Genet Metab. 2012 May. 106(1):104-7. [Medline].\nKrauch G, Wilichowski E, Schmidt KG, Mayatepek E. Pearson marrow-pancreas syndrome with worsening cardiac function caused by pleiotropic rearrangement of mitochondrial DNA. Am J Med Genet. 2002 Jun 1. 110(1):57-61. [Medline].\nMuraki K, Nishimura S, Goto Y, et al. The association between haematological manifestation and mtDNA deletions in Pearson syndrome. J Inherit Metab Dis. 1997 Sep. 20(5):697-703. [Medline].\nSeneca S, De Meirleir L, De Schepper J, et al. Pearson marrow pancreas syndrome: a molecular study and clinical management. Clin Genet. 1997 May. 51(5):338-42. [Medline].\nStoddard RA, McCurnin DC, Shultenover SJ, et al. Syndrome of refractory sideroblastic anemia with vacuolization of marrow precursors and exocrine pancreatic dysfunction presenting in the neonate. J Pediatr. 1981 Aug. 99(2):259-61. [Medline].\nSuperti-Furga A, Schoenle E, Tuchschmid P, et al. Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal haemoglobin caused by deletion and duplication of mitochondrial DNA. Eur J Pediatr. 1993 Jan. 152(1):44-50. [Medline].\nManea EM, Leverger G, Bellmann F, et al. Pearson syndrome in the neonatal period: two case reports and review of the literature. J Pediatr Hematol Oncol. 2009 Dec. 31(12):947-51. [Medline].\nMcShane MA, Hammans SR, Sweeney M, et al. Pearson syndrome and mitochondrial encephalomyopathy in a patient with a deletion of mtDNA. Am J Hum Genet. 1991 Jan. 48(1):39-42. [Medline].\nMorel AS, Joris N, Meuli R, et al. Early neurological impairment and severe anemia in a newborn with Pearson syndrome. Eur J Pediatr. 2009 Mar. 168(3):311-5. [Medline].\nKnerr I, Metzler M, Niemeyer CM, et al. Hematologic features and clinical course of an infant with Pearson syndrome caused by a novel deletion of mitochondrial DNA. J Pediatr Hematol Oncol. 2003 Dec. 25(12):948-51. [Medline].\nLee HF, Lee HJ, Chi CS, Tsai CR, Chang TK, Wang CJ. The neurological evolution of Pearson syndrome: Case report and literature review. Eur J Paediatr Neurol. 2007 Apr 13. [Medline].\nMomont AC, Trobe JD. Transient corneal edema and left hemisphere dysfunction in pearson syndrome. J Neuroophthalmol. 2009 Jun. 29(2):158-9. [Medline].\nAlter BP. Pearson syndrome in a Diamond-Blackfan anemia cohort. Blood. 2014 Jul 17. 124(3):312-3. [Medline]. [Full Text].\nCrippa BL, Leon E, Calhoun A, Lowichik A, Pasquali M, Longo N. Biochemical abnormalities in Pearson syndrome. Am J Med Genet A. 2015 Mar. 167A (3):621-8. [Medline].\nPanda D, Gupta N, Gupta R, Bakhshi S. Pediatric myelodysplastic syndrome with cytoplasmic vacuolation in myeloid precursors. J Pediatr Hematol Oncol. 2011 Jan. 33(1):59-61. [Medline].\nOzbek N, Derbent M, Olcay L, Yilmaz Z, Tokel K. Dysplastic changes in the peripheral blood of children with microdeletion 22q11.2. Am J Hematol. 2004 Oct. 77(2):126-31. [Medline].\nAngotti LB, Post GR, Robinson NS, et al. Pancytopenia with myelodysplasia due to copper deficiency. Pediatr Blood Cancer. 2008 Nov. 51(5):693-5. [Medline].\nGibson KM, Bennett MJ, Mize CE, et al. 3-Methylglutaconic aciduria associated with Pearson syndrome and respiratory chain defects. J Pediatr. 1992 Dec. 121(6):940-2. [Medline].\nSemeraro M, Boenzi S, Carrozzo R, et al. The urinary organic acids profile in single large-scale mitochondrial DNA deletion disorders. Clin Chim Acta. 2018 Jun. 481:156-60. [Medline].\nBaertling F, Meissner T, Troeger A, Pillekamp F, Mayatepek E, Laws HJ, et al. Granulocyte colony stimulating factor for treatment of neutropenia-associated infection in Pearson syndrome. Klin Padiatr. 2014 May. 226(3):190-1. [Medline].\nFaraci M, Cuzzubbo D, Micalizzi C, et al. Allogeneic bone marrow transplantation for Pearson's syndrome. Bone Marrow Transplant. 2007 May. 39(9):563-5. [Medline].\nRinged sideroblast in the bone marrow (iron stain). The dark structures that form a ring around the nucleus are hemosiderin-laden mitochondria. (Light microscopy; 100x; iron stain)\nContributor Information and Disclosures\nZora R Rogers, MD Professor of Pediatrics, University of Texas Southwestern Medical Center; Clinical Director of Hematology, Pauline Allen Gill Center for Cancer and Blood Disorders, Children’s Medical Center Dallas; Consulting Pediatric Hematologist/Oncologist, Parkland Memorial Hospital\nZora R Rogers, MD is a member of the following medical societies: American Academy of Pediatrics, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research, Texas Pediatric Society\nDisclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: BCT Terumo.\nSpecialty Editor Board\nMary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference\nDisclosure: Nothing to disclose.\nJames L Harper, MD Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Associate Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center\nJames L Harper, MD is a member of the following medical societies: American Society of Pediatric Hematology/Oncology, American Federation for Clinical Research, Council on Medical Student Education in Pediatrics, Hemophilia and Thrombosis Research Society, American Academy of Pediatrics, American Association for Cancer Research, American Society of Hematology\nHassan M Yaish, MD Medical Director, Intermountain Hemophilia and Thrombophilia Treatment Center; Professor of Pediatrics, University of Utah School of Medicine; Director of Hematology, Pediatric Hematologist/Oncologist, Department of Pediatrics, Primary Children's Medical Center\nHassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, New York Academy of Sciences, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society\nSharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan\nSharada A Sarnaik, MBBS is a member of the following medical societies: American Society of Hematology, American Society of Pediatric Hematology/Oncology, New York Academy of Sciences, Society for Pediatric Research, Children's Oncology Group, American Academy of Pediatrics, Midwest Society for Pediatric Research\nPrint the entire contents of article\nencoded search term (Pearson Syndrome) and Pearson Syndrome\nRelated Conditions and Diseases\nExocrine Pancreatic Insufficiency\nA 15-Year-Old Girl With Steatorrhea Who Can’t See at Night\nLongitudinal Pancreaticojejunostomy (Puestow Procedure)\nBusting Some Popular Myths About Exocrine Pancreatic Insufficiency\nWhat Is the Appropriate Management of Nonfunctioning Pancreatic Neuroendocrine Tumours Disclosed on Screening in Adult Patients With Multiple Endocrine Neoplasia Type 1?\nDiagnosis and Treatment of Pancreatic Exocrine Insufficiency\nGastroenterology Guidelines: 2017 Midyear Review\nDiseases & Conditions Exocrine Pancreatic Insufficiency\n2001 /viewarticle/900231 Journal Article\nJournal Article Diagnosis and Treatment of Pancreatic Exocrine Insufficiency\n2010 creon-pancreaze-pancrelipase-342069 Drugs\nDrugs pancrelipase\nDiseases & Conditions Pearson Syndrome"