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 metabolic disorders, and LCHAD deficiency appears to be the most frequently diagnosed beta-oxidation defect in Finland. In the vast majority of patients, LCHAD deficiency is caused by a common autosomal recessive mutation G1528C. Like several beta-oxidation defects, it presents during infancy with hypoglycemic coma, hepatic steatosis, and hypocarnitinemia. Other manifestations 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 carriers of LCHAD deficiency are prone to have preeclampsia-related pregnancy complications. Diagnosis is suggested by 3-hydroxylated acylcarnitine species in blood and the definitive diagnosis can be made by measuring intermediates of fatty acid beta-oxidation in fibroblasts or by detecting disease causing mutations. Analysis of the frequency of the G1528C mutation in Finland revealed carrier frequency of 1:240. Because of therapeutic and prenatal diagnostic opportunities in LCHAD deficiency, it is important to recognize this severe disorder early in its course.