Practice Essentials

Pearson 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. Patients may recover from the refractory anemia.

In adulthood a phenotypically milder disorder, chronic progressive external ophthalmoplegia (CPEO), is seen; it is marked by variable ptosis, ophthalmoplegia, and proximal limb weakness.

Pearson 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.

Pearson 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. [QxMD MEDLINE Link].
Blaw ME, Mize CE. Juvenile Pearson syndrome. J Child Neurol. 1990 Jul. 5(3):187-90. [QxMD MEDLINE Link].
Gibson 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. [QxMD MEDLINE Link].
Herst PM, Rowe MR, Carson GM, Berridge MV. Functional Mitochondria in Health and Disease. Front Endocrinol (Lausanne). 2017. 8:296. [QxMD MEDLINE Link]. [Full Text].
Rotig 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. [QxMD MEDLINE Link].
Rotig 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. [QxMD MEDLINE Link].
Rotig 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. [QxMD MEDLINE Link].
Kerr DS. Protean manifestations of mitochondrial diseases: a minireview. J Pediatr Hematol Oncol. 1997 Jul-Aug. 19(4):279-86. [QxMD MEDLINE Link].
De Vivo DC. The expanding clinical spectrum of mitochondrial diseases. Brain Dev. 1993 Jan-Feb. 15(1):1-22. [QxMD MEDLINE Link].
Harding AE, Hammans SR. Deletions of the mitochondrial genome. J Inherit Metab Dis. 1992. 15(4):480-6. [QxMD MEDLINE Link].
Son JS, Seo GH, Kim YM, et al. Clinical and genetic features of four patients with Pearson syndrome: An observational study. Medicine (Baltimore). 2022 Feb 4. 101 (5):e28793. [QxMD MEDLINE Link]. [Full Text].
Farruggia 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. [QxMD MEDLINE Link]. [Full Text].
Williams 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. [QxMD MEDLINE Link].
Krauch 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. [QxMD MEDLINE Link].
Muraki 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. [QxMD MEDLINE Link].
Seneca 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. [QxMD MEDLINE Link].
Stoddard 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. [QxMD MEDLINE Link].
Superti-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. [QxMD MEDLINE Link].
Siri B, D'Alessandro A, Maiorana A, et al. Adrenocortical function in patients with Single Large Scale Mitochondrial DNA Deletions: a retrospective single centre cohort study. Eur J Endocrinol. 2023 Nov 8. 189 (5):485-94. [QxMD MEDLINE Link]. [Full Text].
Manea 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. [QxMD MEDLINE Link].
McShane 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. [QxMD MEDLINE Link].
Anteneova N, Kelifova S, Kolarova H, et al. The Phenotypic Spectrum of 47 Czech Patients with Single, Large-Scale Mitochondrial DNA Deletions. Brain Sci. 2020 Oct 22. 10 (11):[QxMD MEDLINE Link]. [Full Text].
Morel 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. [QxMD MEDLINE Link].
Knerr 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. [QxMD MEDLINE Link].
Lee 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. [QxMD MEDLINE Link].
Momont AC, Trobe JD. Transient corneal edema and left hemisphere dysfunction in pearson syndrome. J Neuroophthalmol. 2009 Jun. 29(2):158-9. [QxMD MEDLINE Link].
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Crippa 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. [QxMD MEDLINE Link].
Panda 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. [QxMD MEDLINE Link].
Ozbek 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. [QxMD MEDLINE Link].
Angotti LB, Post GR, Robinson NS, et al. Pancytopenia with myelodysplasia due to copper deficiency. Pediatr Blood Cancer. 2008 Nov. 51(5):693-5. [QxMD MEDLINE Link].
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Faraci M, Cuzzubbo D, Micalizzi C, et al. Allogeneic bone marrow transplantation for Pearson's syndrome. Bone Marrow Transplant. 2007 May. 39(9):563-5. [QxMD MEDLINE Link].

Media Gallery

Characteristic vacuolization of a hematopoietic precursor in the bone marrow. (Light microscopy; 100x; Wright-Giemsa stain)
Electron photomicrograph of a hematopoietic precursor (normoblast) with vacuolization. (Transmission electron microscopy; original 10,000x)
Ringed 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)

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#author-disclosures{display:block}#author-disclosures.modal-layer{position:relative}#author-disclosures .modal-content{max-height:none}#author-disclosures .close-modal{display:none}

Author

Zora R Rogers, MD Professor of Pediatrics (Emerita), University of Texas Southwestern Medical Center at Dallas

Zora 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

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Novartis for sickle cell disease clinical trials; Phar, Inc for panel on Aplastic Anemia<br/>Received income in an amount equal to or greater than $250 from: Up to Date-Topic Cards on SDS and SCD; Leidos-grant reviewer for DOD Congressionally Mandated Research:Bone Marrow Failure Research Program; BeTheMatch -vice chair federal BMT CTN DSMB #1, Executive Committee Section on Hematology Oncology (SOHO) of AAP.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

James 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

James 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

Disclosure: Nothing to disclose.

Chief Editor

Hassan 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

Hassan M Yaish, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Michigan State Medical Society, New York Academy of Sciences

Disclosure: Nothing to disclose.

Additional Contributors

Sharada A Sarnaik, MBBS Professor of Pediatrics, Wayne State University School of Medicine; Director, Sickle Cell Center, Associate Hematologist/Oncologist, Children's Hospital of Michigan

Sharada 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

Disclosure: Nothing to disclose.

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