Adolescent myopathic presentation in two sisters with very long-chain acyl-CoA dehydrogenase deficiency

Two sisters were investigated at the ages of 20 and 13 years owing to persi stently increased serum creatine kinase and recurrent episodes of rhabdomyo lysis after emotional stress in the older and myalgias in the younger. The finding of increased levels of cis-5-tetradecenoic acid (C-14:1) in plasma, severe hypocarnitinaemia and the absence of a pathological dicarboxylic ac iduria in both sisters suggested a very long-chain acyl-CoA dehydrogenase ( VLCAD) deficiency. Reduced [1-C-14]palmitate oxidation and deficient mitoch ondrial VLCAD activity in fibroblasts were found. Mutation analysis reveale d compound heterozygosity for Asp(365)His and Arg(410)His changes. This lat e-onset, milder clinical presentation differs from the other two more sever e infantile phenotypes described, since there is no hypoglycaemia or cardia c disease. Fatty acid oxidation defects should be investigated in all cases with rhabdomyolysis beginning in adolescence or early adulthood.