The frequency of mitochondrial diseases among patients with childhood encephalopathies and myopathies in a defined population of Northern Finland was investigated at the University of Oulu, Finland. Among a total of 116 consecutive patients with unexplained psychomotor retardation enrolled during a 7-year period, the frequency of ultrastructural mitochondrial abnormalities was 71% (ragged-red fibres in 4 cases), oxidative phosphorylation defect (OXPHOS) occurred in 28% (complex I and IV most commonly), and mutations in mitochondrial DNA (mtDNA) in only 1 patient (.9%). A diagnosis of mitochondrial disease was possible (with ultrastructural changes in muscle mitochondria) in 71%, probable (with defects in OXPHOS enzymes in addition to ultrastructural changes) in 15%, and definite (having pathogenic mutations in mtDNA) in 0.9%. Clinical manifestations were mental retardation alone or with hypotonia, ataxia, epilepsy, or spasticity in 74%, and muscular hypotonia or ataxia in 14%. EMG and NCS showed myopathy in 13%, nerve degeneration in 7%, and anterior horn cell disease in 2%. MRI or CT showed cortical atrophy in 18% and calcifications in 6%. Blood lactate was elevated in 58%. [1]

COMMENT. Biochemical and ultrastructural abnormalities indicative of mitochondrial disease are sufficiently frequent to recommend muscle biopsy as an important diagnostic examination in children with unexplained mental retardation. Both ultrastructural mitochondrial abnormalities and decreased activity of 1 or more respiratory chain enzymes are required for a probable diagnosis of mitochondrial disease. The commonly known mtDNA mutations are a rare cause of childhood encephalomyopathies, in contrast to the adult form that frequently shows the MELAS mutation.

Mitochondrial DNA (mtDNA) defects in neuromuscular disorders are reviewed by Marin-Garcia J. and Goldenthal MJ [2] at the Molecular Cardiology Institute, Highland Park, NJ. Mitochondrial mtDNA deletions were found in 1 child with Kearns-Sayre disease, 1 with stroke/CADASIL, and 1 with progressive external ophthalmoplegia, hypotonia, developmental delay, and lactic acidosis. Reduced mtDNA levels occurred in 2 children with encephalomyopathy, hypotonia, lactic acidosis, and mtDNA depletion. Pathogenic mtDNA point mutations are maternally inherited, and most are located in tRNA and rRNA genes.