Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is one of the recently discovered defects of mitochondrial fatty acid beta-oxidation. As a group, the beta-oxidation defects are among the most common inherited me tabolic disorders, and LCHAD deficiency appears to be the most frequently d iagnosed beta-oxidation defect in Finland. In the vast majority of patients , LCHAD deficiency is caused by a common autosomal recessive mutation G1528 C. Like several beta-oxidation defects, it presents during infancy with hyp oglycemic coma, hepatic steatosis, and hypocarnitinemia. Other manifestatio ns are cardiomyopathy and rhabdomyolysis, which are frequent in defects of long-chain fatty acid oxidation. In addition, LCHAD deficiency has specific features, namely peripheral neuropathy and chorioretinopathy. Female carri ers of LCHAD deficiency are prone to have preeclampsia-related pregnancy co mplications. Diagnosis is suggested by 3-hydroxylated acylcarnitine species in blood and the definitive diagnosis can be made by measuring intermediat es of fatty acid beta-oxidation in fibroblasts or by detecting disease caus ing mutations. Analysis of the frequency of the G1528C mutation in Finland revealed carrier frequency of 1:240. Because of therapeutic and prenatal di agnostic opportunities in LCHAD deficiency, it is important to recognize th is severe disorder early in its course.