Mitochondrial DNA Deletion in a Child With Mitochondrial Encephalomyopathy,Growth Hormone Deficiency,and Hypoparathyroidism

Abstract

We report an 11-year-old boy with short stature, bilateral ptosis, sensorineural hearing loss, muscle weakness, and endocrine abnormalities. Brain magnetic resonance imaging (MRI) showed a bilateral abnormal signal in the globus pallidus and in the midbrain tegment. Muscle biopsy specimens showed ragged red and cytochrome c oxidase negative fibers, and biochemical analysis of muscle homogenate showed a partial defect of complex I and IV activities of the respiratory chain enzymes. Analysis of mitochondrial DNA by a polymerase chain reaction screening procedure and Southern blot revealed a novel heteroplasmic single mitochondrial DNA deletion of 7.8 kb in different tissues. This deletion was absent in the blood DNA of his mother and brother. This case further expands and confirms the wide clinical spectrum of mitochondrial disorders associated with single large-scale mitochondrial DNA deletions. (J Child Neurol 2006;21:983—985; DOI 10.2310/7010.2006.00218).

Get full access to this article

View all access options for this article.

References

DiMauro S. , Andreu AL , De Vivo DC : Mitochondrial disorders. J Child Neurol 2002 ;17(Suppl 3):3S35—S45.

Chinnery PF , DiMauro S. , Shanske S. , et al: Risk of developing a mitochondrial DNA deletion disorder. Lancet 2004;364:592—596.

Nicolino M. , Ferlin T. , Forest M. , et al: Identification of a large-scale mitochondrial deoxyribonucleic acid deletion in endocrinopathies and deafness: Report of two unrelated cases with diabetes mellitus and adrenal insufficiency, respectively. J Clin Endocrinol Metab 1997;82:3063—3067.

Gucuyener K. , Seyrantepe V. , Topaloglu H. , Ozguc M. : Mitochondrial deletion in a boy with growth hormone deficiency mimicking cerebral palsy. J Inherit Metab Dis 1998;21:173—174.

Bruno C. , Gandullia P. , Santorelli FM , et al: Tubulopathy, endocrinopathies and encephalomyopathy in a child with a novel large-scale mitochondrial DNA deletion. Clin Genet 2002;61:465—467.

Niaudet P. , Heidet L. , Munnich A. , et al: Deletion of the mitochondrial DNA in a case of de Toni-Debré-Fanconi syndrome and Pearson syndrome. PediatrNephrol 1994;8:164-168.

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

Bruno C. , Biancheri R. , Garavaglia B. , et al: A novel mutation in the SURF1 gene in a child with Leigh disease, peripheral neuropathy, and cytochrome-c oxidase deficiency. J Child Neurol 2002;17:233—236.

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.

10.

Moraes CT , DiMauro S. , Zeviani M. , et al: Mitochondrial DNA deletions in progressive external ophthalmoplegia and Kearns-Sayre syndrome. N Engl J Med 1989 ;320:1293—1299.

11.

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;18:561—567.

12.

Harvey JN , Barnett D. : Endocrine dysfunction in Kearns-Sayre syndrome. Clin Endocrinol (Oxf) 1992;37:97—103.

13.

Matsuzaki M. , Izumi T. , Shishikura K. , et al: Hypothalamic growth hormone deficiency and supplementary GH therapy in two patients with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. Neuropediatrics 2002;33:271—273.