Myophosphorylase deficiency associated with a defect in complex I of the mitochondrial respiratory chain

We studied a 21-year-old patient with clinical, biochemical and histochemic al evidence of myophosphorylase deficiency and unusual repetitive episodes of pigmenturia. His muscle biopsy also revealed morphological signs of mito chondrial proliferation and a defect of complex I of the respiratory chain. His mother had exercise intolerance without myoglobinuria and no histochem ical evidence of myophosphorylase deficiency. In muscle, the mother showed some ragged-red fibers, normal respiratory chain levels and a significant r esidual phosphorylase activity. Molecular genetic analysis revealed that th e proband was homozygous for the mutation commonly found in McArdle's disea se. The mother, father, and the five siblings were all heterozygous for the same mutation. Mitochondrial DNA analysis of the proband's muscle failed t o demonstrate known mutations associated with his clinical pattern. Moreove r, we sequenced his tRNA(Leu(UUR)) gene, a hot spot for mutations, showing no abnormality. (C) 1998 Elsevier Science B.V. All rights reserved.