CLINICAL MANIFESTATIONS OF MITOCHONDRIAL-DNA DEPLETION

Objective: We studied five new patients with mitochondrial DNA (mtDNA) depletion to better define the clinical spectrum of this disorder. Ba ckground: mtDNA depletion has been associated with myopathy or hepatop athy, or both, in infants and young children. Involvement of the CNS a nd peripheral nervous system has not been clearly established. Methods : We reviewed the clinical course and performed morphologic, biochemic al, and genetic analyses of muscle samples from five patients. Results : Age at onset ranged from 3 months to 5 years, and one patient surviv ed until age 101/2 years. Two patients had laboratory and clinical fea tures reminiscent of dystrophinopathy, two had evidence of brain invol vement, and two had peripheral neuropathy. Muscle biopsy specimens in all patients showed abundant ragged-red fibers. Biochemistry showed cy tochrome c oxidase deficiency in all patients tested and decreased act ivities of other respiratory chain complexes in some. Conclusions: Inh eritance appeared to be autosomal recessive, suggesting that mutations in nuclear DNA are responsible for mtDNA depletion. mtDNA depletion s hould be considered in children with mitochondrial disorders of uncert ain etiology, and criteria for diagnosis are proposed.