A novel mutation of late-onset very-long-chain acyl-CoA dehydrogenase deficiency

Abstract 

We describe a novel mutation in three patients with the myopathic form of very-long-chain acyl-CoA dehydrogenase deficiency. Three siblings born to second-degree cousins of Jewish-Iraqi origin exhibited rhabdomyolysis and myoglobinuria as the presenting signs of the mild late-onset form of very-long-chain acyl-CoA dehydrogenase deficiency. We screened the patients for mutations in the very-long-chain acyl-CoA dehydrogenase gene by amplification of all 20 exons and analysis by single-stranded conformation variance on gel electrophoresis. The patients were homozygous for a novel mutation G637A that alters alanine 173 to threonine. We hypothesize that this missense substitution caused a mild change of enzyme function correlating with the mild clinical features and, thus, favoring a genotype-phenotype correlation.