FATAL MITOCHONDRIAL MYOPATHY, LACTIC-ACIDOSIS, AND COMPLEX-I DEFICIENCY ASSOCIATED WITH A HETEROPLASMIC A-]G MUTATION AT POSITION-3251 IN THE MITOCHONDRIAL TRNALEU(UUR) GENE

A girl, who died at 14 years of age from a rapidly progressive mitocho ndrial myopathy, was found to be heteroplasmic for a mutation in the m itochondrial tRNALeu(UUR) gene at position 3251. A large proportion of muscle fibres contained accumulations of abnormal mitochondria but no cytochrome c oxidase deficient fibres were present. Polarographic and enzymatic measurements on isolated muscle mitochondria revealed a pro found isolated complex I deficiency. A high percentage of mutant mtDNA was found in muscle (94%), fibroblasts (93%), brain (90%), liver (80% ), and heart (79%), The family was not available for investigation. Fo r genotype to phenotype correlation studies, we investigated the propo rtion of mutated mtDNA in single muscle fibres of normal appearance an d muscle fibres with accumulations of mitochondria, The proportion of mutant mtDNA was 28% (range < 0.3%-86%) in normal-appearing fibres and 6l% (range 15%-88%) in abnormal fibres. The difference in the proport ion of mutant mtDNA was highly significant (P < 0.001) between the two groups of fibres.