Mitochondrial DNA Deletion in a Child Mitochondrial DNA Deletion in a Child With Megaloblastic Anemia and Recurrent Encephalopathy

Abstract

A 3½-year-old boy presented with megaloblastic anemia and recurrent episodes of severe lactic acidosis and coma. At age 4 years, he developed sepsis and died; postmortem examination failed to show any gross abnormality in any tissue. Biochemical analysis of muscle showed decreased activities for all respiratory chain enzymes except complex II. Muscle histochemistry revealed diffuse cytochrome c oxidase deficiency. Southern blot analysis of mitochondrial DNA from muscle, liver, and blood showed a heteroplasmic single mitochindrial DNA deletion of 2.4 kb, which removed the genes for cytochrome c oxidase I and II and the transfer ribonucleic acid genes for serine and aspartic acid. Single large-scale deletions in mitochondrial DNA have been associated with Pearson's syndrome, Kearns-Sayre syndrome, and progressive external ophthalmoplegia. This patient's presentation is unusual and suggests an overlap between Pearson's syndrome and Kearns-Sayre syndrome. (J Child Neurol 2004;19:258-261).

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References

DiMauro S. , Bonilla E. , Davidson M. , et al: Mitochondria in neuromuscular disorders. Biochem Biophys Acta 1998;1366:199-210.

Zeviani M. , Moraes CT , DiMauro S. , et al: Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 1988;38: 1339-1346.

Moraes CT , DiMauro S. , Zeviani M. , et al: Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 1989 ;32:1293-1299.

Rötig A. , Cormier V. , Blanche S. , et al: Pearson's marrow-pancreas syndrome. A multisystem mitochondrial disorder in infancy. J Clin Invest 1990;86:1601-1608.

Cormier V. , Rotig A. , Quartino AR , et al: Widespread multi-tissue deletions of the mitochondrial genome in the Pearson marrow-pancreas syndrome. J Pediatr 1990;117:599-602.

DiMauro S. Servidei S. Zeviani M. , et al: Cytochrome c oxidase deficiency in Leigh syndrome. Ann Neurol 1987;22:498-506.

Zupanc ML , Moraes C. , Shanske S. , et al: Deletion of mtDNA in patients with combined features of Kearns-Sayre and MELAS syndrome. Ann Neurol 1991;29:680-683.

Santorelli FM , Barmada MA , Pons R. , et al: Leigh-type neuropathology in Pearson syndrome associated with impaired ATP production and a novel mtDNA deletion . Neurology 1996; 47:1320-1323.

Cormier V. , Rotig A. , Tardieu M. , et al: Autosomal dominant deletions of the mitochondrial genome in a case of progressive encephalopathy. Am J Hum Genet 1991;48:643-648.

10.

Pearson HA , Lobel JS , Kocoshis SA , et al: A new syndrome of refractory sideroblastic anemia with vacuolization of marrow precursor and exocrine pancreatic dysfunction. J Pediatr 1979;95:976-984.

11.

Eviatar L. , Shanske S. , Gauthier B. , et al: Kearns-Sayre syndrome presenting as renal tubular acidosis. Neurology 1990;40:1761-1763.

12.

Rötig A. , Bourgeron T. , Chretien D. , et al: Spectrum of mitochondrial DNA rearrangements in the Pearson marrow-pancreas syndrome. Hum Mol Genet 1995 ;14:1327-1330.

13.

Superti-Furga A. , Tuchschmid P. , Caduff R. , et al: Pearson bone marrow-pancreas syndrome with insulin-dependent diabetes, progressive renal tubulopathy, organic aciduria and elevated fetal hemoglobin caused by deletion and duplication of mitochondrial DNA. Eur J Pediatr 1993;152:44-50.

14.

McShane MA , Hammans SR , Sweeney M. , et al: Pearson syndrome and mitochondrial encephalopathy in a patient with a deletion of mtDNA. Am J Hum Genet 1991 ,48:39-42.

15.

Muraki K. , Nishimura S. , Goto Y. , et al: The association between hematological manifestations and mtDNA deletions in Pearson syndrome. J Inherit Metab Dis 1997;20:697-703.

16.

De Vries DD , Buzing JM , Ruitenbeek W. , et al: Myopathology and a mitochondrial DNA deletion in the Pearson marrow and pancreas syndrome. Neuromuscul Disord 1992;2:185-195.

17.

Fischel-Ghodsian N. , Bohlman MC , Prezant TR , et al: Deletion in blood mitochondrial DNA in Kearns-Sayre syndrome. Pediatr Res 1992 ;31:557-560.