A Large-Scale Mitochondrial DNA Deletion Causing Progressive Ataxia

Abstract

Mitochondrial diseases are characterized by heteroplasmic mitochondrial DNA mutations and multisystemic dysfunction. Base substitutions of mitochondrial DNA have been reported in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), ^1,2 myoclonus epilepsy with ragged red fibers (MERRF), ³ and other neuromuscular disorders.⁴ Heteroplasmic mitochondrial DNA deletions are usually detected in chronic external ophthalmoplegia, including Kearns-Sayre syndrome, ⁵ and on rare occasions in Pearson marrow-pancreas syndrome.⁶ A few unusual clinical complexes associated with single mitochondrial DNA deletions have been reported, such as maternally transmitted diabetes and deafness,⁷ diffuse leukodystrophy,⁸ MELAS, Fanconi's syndrome,9 pure myopathy and neuropathy,¹⁰ myopathy with lipomatosis, ¹¹ and Leigh-type neuropathology.¹²

We report here a patient with a large-scale mitochondrial DNA deletion, which was located at a novel site and produced an atypical Kearns-Sayre syndrome phenotype. The major clinical sign at the early stage was not ophthalmoplegia, but cerebellar ataxia.