Five children with mitochondrial myopathy associated with depletion of muscle mtDNA are reported from the Departments of Neurology and Genetics and Development, Columbia University College of Physicians and Surgeons, New York, NY and other centers in Germany, Belgium and the U.S. Symptoms manifested within or soon after the first year of life and muscle biopsies showed ragged red fibers and decreased respiratory chain activity. There was good correlation between clinical severity and degree of mtDNA depletion in muscle. An infant who died at 2 months had lactic acidosis and less than 2% of the normal level of mtDNA, while 4 children with relatively milder myopathy had no lactic acidosis and 8-34% residual mtDNA. 
COMMENT. Depletion of mtDNA is considered a distinct entity distinguished from other known mitochondrial disorders with COX deficiency or with multiple respiratory chain defects (fatal and benign infantile myopathies, Leigh’s syndrome, Kearns-Sayre syndrome). The principal clinical features of patients with mtDNA depletion and mitochondrial myopathy are weakness, hypotonia and respiratory distress.