Early-onset fatal encephalomyopathy associated with severe mtDNA depletion

Abstract We studied a 3-month-old girl who was admitted to hospital because of respiratory distress. The clinical course was characterized by a rapidly progressive generalized hypotonia with lactic acidosis and she died at 4 months of age. A muscle biopsy showed few ragged-red fibres and lack of histochemical cytochrome c oxidase reaction in all fibres. Enzyme activities of the respiratory chain complexes containing subunits encoded by the mitochondrial DNA (mtDNA) were markedly decreased. A quantitative Southern blot analysis revealed 99% depletion of mtDNA in muscle and normal amounts in blood. There was no family history and the dizygotic twin sister of the patient was no symptomatic.