Objective: We studied five new patients with mitochondrial DNA (mtDNA) depletion to better define the clinical spectrum of this disorder.
Background: mtDNA depletion has been associated with myopathy or hepatopathy, or both, in infants and young children. Involvement of the CNS and peripheral nervous system has not been clearly established.
Methods: We reviewed the clinical course and performed morphologic, biochemical, and genetic analyses of muscle samples from five patients.
Results: Age at onset ranged from 3 months to 5 years, and one patient survived until age 10 1/2 years. Two patients had laboratory and clinical features reminiscent of dystrophinopathy, two had evidence of brain involvement, and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed abundant ragged-red fibers. Biochemistry showed cytochrome c oxidase deficiency in all patients tested and decreased activities of other respiratory chain complexes in some.
Conclusions: Inheritance appeared to be autosomal recessive, suggesting that mutations in nuclear DNA are responsible for mtDNA depletion. mtDNA depletion should be considered in children with mitochondrial disorders of uncertain etiology, and criteria for diagnosis are proposed.