Rivista di formazione e aggiornamento professionale del pediatra e del medico di base, fondata nel 1982. In collaborazione con l'Associazione Culturale Pediatri.
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Problemi speciali

La sindrome di Pearson

Pearson syndrome

Piero Farruggia1, Floriana Di Marco1, Carlo Dufour2

1Oncoematologia Pediatrica, ARNAS Ospedali “Civico, Di Cristina e Benfratelli”, Palermo
2Ematologia, Istituto “G. Gaslini”, Genova

Giugno 2018 - pagg. 371 -377

Abstract
Pearson syndrome is a sporadic and very rare progressive generalised disorder with heterogeneity in clinical expression classically associated with single large-scale deletions of mitochondrial DNA: it is characterised by refractory sideroblastic anaemia during infancy. The general improvement of support therapy probably explains the better survival rate reported in more recent series. Its prognosis remains poor, but early diagnosis will help to improve clinical course.
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Bibliografia
1. 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;95(6):976-84. 2. Rötig A, Collonna M, Bonnefont JP, et al. Mitochondrial DNA deletion in Pearson’s marrow/pancreas syndrome. Lancet 1989;1 (8643):902-3. 3. Rötig A, Cormier V, Blanche S, et al. Pearson’s marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 1990;86(5):1601-8. 4. Rötig A, Bourgeron T, Chretien D, Rustin P, Munnich A. Spectrum of mitochondrial DNA rearrangements in the Pearson marrow- pancreas syndrome. Hum Mol Genet 1995;4:1327-30. 5. Broomfield A, Sweeney MG, Woodward CE, et al. Paediatric single mitochondrial DNA deletion disorders: an overlapping spectrum of disease. J Inherit Metab Dis 2015;38 (3):445-57. 6. Farruggia P, Di Cataldo A, Pinto RM, et al. Pearson Syndrome: a retrospective cohort study from the marrow failure study group of AIEOP (Associazione Italiana Emato-Oncologia Pediatrica). JIMD Rep 2016;26:37-43. 7. Gorman GS, Schaefer AM, Ng Y, et al. Prevalence of nuclear and mitochondrial DNA mutations related to adult mitochondrial disease. Ann Neurol 2015;77(5):753-9. 8. Chinnery PF, Johnson MA, Wardell TM, et al. The epidemiology of pathogenic mitochondrial DNA mutations. Ann Neurol 2000;48 (2):188-93. 9. Chinnery PF, Turnbull DM. Epidemiology and treatment of mitochondrial disorders. Am J Med Genet 2001;106(1):94-101. 10. Giles RE, Blanc H, Cann HM, Wallace DC. Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 1980;77(11):6715-9. 11. Rötig A, Poulton J. Genetic causes of mitochondrial DNA depletion in humans. Biochim Biophys Acta 2009;1792(12):1103-8. 12. Tuppen HA, Blakely EL, Turnbull DM, Taylor RW. Mitochondrial DNA deletions and human disease. Biochim Biophys Acta 2010; 1797(2):113-28. 13. Haigis MC, Yankner BA. The aging stress response. Mol Cell 2010;40(2):333-44. 14. Krishnan KJ, Reeve AK, Samuels DC, et al. What causes mitochondrial DNA deletions in human cells? Nat Genet 2008;40(3):275-9. 15. Schon EA, Di Mauro S, Hirano M. Human mitochondrial DNA: roles of inherited and somatic mutations. Nat Rev Genet 2012;13(12): 878-90. 16. Kisler JE, Whittaker RG, McFarland R. Mitochondrial diseases in childhood: a clinical approach to investigation and management. Dev Med Child Neurol 2010;52(5):422-33. 17. Mita S, Rizzuto R, Moraes CT, et al. Recombination via flanking direct repeats is a major cause of large-scale deletions of human mitochondrial DNA. Nucleic Acids Res 1990; 18(3):561-7. 18. Thorburn DR, Dahl HH. Mitochondrial disorders: genetics, counseling, prenatal diagnosis and reproductive options. Am J Med Genet 2001;106(1):102-14. 19. Chen X, Prosser R, Simonetti S, Sadlock J, Jagiello G, Schon EA. Rearranged mitochondrial genomes are present in human oocytes. Am J Hum Genet 1995;57(2):239-47. 20. Bernes SM, Bacino C, Prezant TR, et al. Identical mitochondrial DNA deletion in mother with progressive external ophthalmoplegia and son with Pearson marrow-pancreas syndrome. J Pediatr 1993;123(4):598-602. 21. Shanske S, Tang Y, Hirano M, et al. Identical mitochondrial DNA deletion in a woman with ocular myopathy and in her son with Pearson syndrome. Am J Hum Genet 2002;71 (3):679-83. 22. Ozawa T, Yoneda M, Tanaka M, et al. Maternal inheritance of deleted mitochondrial DNA in a family with mitochondrial myopathy. Biochem Biophys Res Commun 1988; 154(3):1240-7. 23. Larsson NG, Holme E, Kristiansson B, Oldfors A, Tulinius M. Progressive increase of the mutated mitochondrial DNA fraction in Kearns-Sayre syndrome. Pediatr Res 1990;28 (2):131-6. 24. Jokinen R, Marttinen P, Sandell HK, et al. Gimap3 regulates tissue-specific mitochondrial DNA segregation. PLoS Genet 2010;6 (10):e1001161. 25. Marchington DR, Macaulay V, Hartshorne GM, Barlow D, Poulton J. Evidence from human oocytes for a genetic bottleneck in an mtDNA disease. Am J Hum Genet 1998;63 (3):769-75. 26. Graff C, Wredenberg A, Silva JP, Bui TH, Borg K, Larsson NG. Complex genetic counselling and prenatal analysis in a woman with external ophthalmoplegia and deleted mtDNA. Prenat Diagn 2000;20(5):426-31. 27. Gussi IL, Rahimian H, Stanescu Popp AM. Prenatal features of an uncommon specific mitochondrial cytopathy - the Pearson syndrome. Ultrasound in Obstetrics & Gynecology 2009;34 (Suppl. 1):177-284. 28. Fellman V, Kotarsky H. Mitochondrial hepatopathies in the newborn period. Semin Fetal Neonatal Med 2011;16(4):222-8. 29. 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;31(12):947-51. 30. Lohi O, Kuusela AL, Arola M. A novel deletion in a Pearson syndrome infant with hypospadias and cleft lip and palate. J Inherit Metab Dis 2005;28(6):1165-6. 31. Gürgey A, Ozalp I, Rötig A, et al. A case of Pearson syndrome associated with multiple renal cysts. Pediatr Nephrol 1996;10(5):637-8. 32. Munakata K, Bundo M, Kato T, et al. Coexisting point mutations of mitochondrial DNA in a patient with a heart abnormality and Pearson syndrome-like symptoms. Am J Med Genet A 2005;139A(2):162-4. 33. Pathak S, Sethi A, Gupta N, Ranasaria M. Proximal renal tubular acidosis due to mitochondrial cytopathy: a case report. IJRRMS 2014;4(3):23-7. 34. Morel AS, Joris N, Meuli R, et al. Early neurological impairment and severe anemia in a newborn with Pearson syndrome. Eur J Pediatr 2009;168(3):311-5. 35. Mancuso M, Orsucci D, Angelini C, et al. Redefining phenotypes associated with mitochondrial DNA single deletion. J Neurol 2015;262(5):1301-9. 36. Crippa BL, Leon E, Calhoun A, Lowichik A, Pasquali M, Longo N. Biochemical abnormalities in Pearson syndrome. Am J Med Genet A 2015;167°(3):621-8. 37. 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;106(1):104-7. 38. Atale A, Bonneau-Amati P, Rötig A, et al. Tubulopathy and pancytopaenia with normal pancreatic function: a variant of Pearson syndrome. Eur J Med Genet 2009;52(1):23-6. 39. Inoue S, Yokota M, Nakada K, Miyoshi H, Hayashi J. Pathogenic mitochondrial DNA-induced respiration defects in hematopoietic cells result in anemia by suppressing erythroid differentiation. FEBS Lett 2007;581(9): 1910-6. 40. Gümrük F, Kuşkonmaz B, Coşkun T. Pearson syndrome associated with hemophagocytic syndrome in a child. Turk J Haematol 2008;25(1):54-5. 41. Gagne KE, Ghazvinian R, Yuan D, et al. Pearson marrow pancreas syndrome in patients suspected to have Diamond-Blackfan anemia. Blood 2014;124(3):437-40. 42. Hoyoux C, Dresse MF, Robinet S, et al. Cord blood transplantation in a child with Pearson’s disease. Pediatr Blood Cancer 2008;51(4):566. 43. Tumino M, Meli C, Farruggia P, et al. Clinical manifestations and management of four children with Pearson syndrome. Am J Med Genet A 2011;155A(12):3063-6. 44. Santorelli FM, Barmada MA, Pons R, Zhang LL, DiMauro S. Leigh-type neuropathology in Pearson syndrome associated with impaired ATP production and a novel mtDNA deletion. Neurology 1996;47(5):1320- 3. 45. Momont AC, Trobe JD. Transient corneal edema and left hemisphere dysfunction in Pearson syndrome. J Neuroophthalmol 2009; 29(2):158-9. 46. Cursiefen C, Küchle M, Scheurlen W, Naumann GO. Bilateral zonular cataract associated with the mitochondrial cytopathy of Pearson syndrome. Am J Ophthalmol 1998; 125(2):260-1. 47. Arzanian MT, Eghbali A, Karimzade P, Ahmadi M, Houshmand M, Rezaei N. mtDNA deletion in an Iranian infant with Pearson marrow syndrome. Iran J Pediatr 2010;20(1): 107-12. 48. Lacbawan F, Tifft CJ, Luban NL, et al. Clinical heterogeneity in mitochondrial DNA deletion disorders: a diagnostic challenge of Pearson syndrome. Am J Med Genet 2000;95 (3):266-8. 49. Gibson KM, Bennett MJ, Mize CE, et al. 3-Methylglutaconic aciduria associated with Pearson syndrome and respiratory chain defects. J Pediatr 1992;121(6):940-2. 50. Lichter-Konecki U, Trefz FK, Rötig A, Munnich A, Pfeil A, Bremer HJ. 3-Methylglutaconic aciduria in a patient with Pearson syndrome. Eur J Pediatr 1993;152(4):378. 51. Sanderson S, Green A, Preece MA, Burton H. The incidence of inherited metabolic disorders in the West Midlands, UK. Arch Dis Child 2006;91(11):896-9. 52. 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;152(1):44-50. 53. Aljurf M, Gluckman E, Dufour C (Eds). Severe congenital neutropenias and other rare congenital marrow failures. In: Congenital and acquired bone marrow failures. Elsevier, 2017. 54. Faraci M, Cuzzubbo D, Micalizzi C, et al. Allogeneic bone marrow transplantation for Pearson’s syndrome. Bone Marrow Transplant 2007;39(9):563-5. 55. Seneca S, De Meirleir L, De Schepper J, et al. Pearson marrow pancreas syndrome: a molecular study and clinical management. Clin Genet 1997;51(5):338-42. 56. Parikh S, Saneto R, Falk MJ, Anselm I, Cohen BH, Haas R, Medicine Society TM. A modern approach to the treatment of mitochondrial disease. Curr Treat Options Neurol 2009;11(6):414-30. 57. Lee CK, Klopp RG, Weindruch R, Prolla TA. Gene expression profile of aging and its retardation by caloric restriction. Science 1999;285(5432):1390-3.

Corrispondenza: piero.farruggia@arnascivico.it