Kearns-Sayre Syndrome With a Novel Mitochondrial DNA Deletion

Abstract

We describe a 17-year-old boy with a clinical neurologic picture consistent with Kearns-Sayre syndrome. His manifestations included progressive external ophthalmoplegia, bilateral ptosis, retinitis pigmentosa, and muscle weakness. He was found to harbor an abundant novel deletion in skeletal muscle mitochondrial DNA. Biochemical analysis of the patient's biopsied skeletal muscle showed that the specific activities of all four respiratory complexes with mitochondrial DNA-encoded subunits were markedly reduced in contrast to normal activity levels of entirely nuclear DNA-encoded enzyme activities (eg, complex II and citrate synthase). Ultrastructural analysis also indicated the presence of strikingly abnormal mitochondria with both unusual cristae and frequent paracrystalline inclusions. The great amount of the deleted mitochondrial DNA in this patient's muscle, as well as the concomitant reduction in specific respiratory complex activity, suggests that the mitochondrial DNA deletion plays a role in the pathogenesis of this neurologic disease. (J Child Neurol 2000;15:555-558).

Get full access to this article

View all access options for this article.

References

Marin-Garcia J. , Goldenthal MJ , Pierpont ME , et al: Impaired mitochondrial function in idiopathic dilated cardiomyopathy: Biochemical and molecular analysis . J Card Fail 1995;1:285-292.

Schon EA , Bonilla E. , DiMauro S. : Mitochondrial DNA mutations and pathogenesis. J Bioenerg Biomembr 1997;29:131-149.

Marin-Garcia J. , Goldenthal MJ , Ananthakrishnan R. , et al: Specific mitochondrial DNA deletions in idiopathic dilated cardiomyopathy. Cardiovasc Res 1996;31:306-314.

Anderson S. , Bankier AT , Barrell BG , et al: Sequence and organization of the human mitochondrial genome . Nature 1981;290:457-465.

Rowland LP , Blake D. , Hirano M. , et al: Clinical syndromes associated with ragged red fibers. Rev Neurol 1991 ; 147:467-473.

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 ;320:1293-1299.

Holt IJ , Harding AE , Morgan-Hughes JA : Deletions of mtDNA in patients with mitochondrial myopathies. Nature 1988;331:717-719.

Zeviani M. , Servidei S. , Gellera C. : An autosomal dominant disorder with multiple deletions of mitochondrial DNA at the D-loop region. Nature 1989;339:309-311.

10.

Wallace DC , Lott MT , Brown MD , et al: Report of the committee on human mitochondrial DNA. Online database , 1995: www.infinity.gen.emory.edu/mitomap.html .