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.
Tyni
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T
Unit of Child Neurology, Hospital for Children and Adolescents, Helsinki University Central Hospital, Finland.
Pihko
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H
D015094:3-Hydroxyacyl CoA Dehydrogenases / Q000172:deficiency*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005387:Finland / Q000453:epidemiology; D005787:Gene Frequency; D006580:Genetic Carrier Screening; D006801:Humans; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D010084:Oxidation-Reduction; D011247:Pregnancy
D005227:Fatty Acids; D015094:3-Hydroxyacyl CoA Dehydrogenases