Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an autosomal recessive disorder of mitochondrial fatty acid oxidation. Apart from life-threatening metabolic derangement with hypoketotic hypoglycemia, patients often show liver disease, cardiomyopathy, and neuropathy. A common mutation (1528GϾC) in the gene coding for the ␣-subunit of the mitochondrial trifunctional protein harboring LCHAD activity is found in 87% of the alleles of patients. LCHAD is considered a rare disorder with only 63 patients reported in the literature. Whether this is due to a truly low prevalence of the disorder or because many patients remain unrecognized as a result of aspecific symptomatology is not clear. A remarkable association between LCHAD deficiency and the hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, which is a severe complication of pregnancy, has been reported. Because of this, we studied the frequency of the common LCHAD mutation in the Dutch population by analyzing 2047 Guthrie cards and 113 women who had suffered from HELLP syndrome. To be able to perform this large-scale study in dried bloodspots, we developed a new sensitive PCR-restriction fragment length polymorphism method. The carrier frequency for the common LCHAD mutation in the Dutch population was found to be low (1:680), consistent with the observed low incidence of the disorder. In the group of women with a history of HELLP syndrome, the prevalence of the common LCHAD mutation was also low (1:113). We conclude that LCHAD deficiency is, indeed, a rare disorder and that heterozygosity for the common mutation is not a major cause of the HELLP syndrome. (Pediatr Res 48: 151-154, 2000) Abbreviations AFLP, acute fatty liver of pregnancy HELLP, hemolysis, elevated liver enzymes, and low platelets LCHAD, long-chain 3-hydroxyacyl-CoA dehydrogenase MCAD, medium-chain acyl-CoA dehydrogenase PCR-RFLP, PCR-restriction fragment length polymorphism LCHAD deficiency is one of the 13 inborn errors of mitochondrial fatty acid oxidation currently known. In patients with LCHAD deficiency, the oxidation of long-chain fatty acids is impaired due to mutations in the gene coding from the ␣-subunit of the mitochondrial trifunctional protein. The latter protein is an octamer of four ␣-and four -subunits. The ␣-subunit harbors the enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase activities, whereas the -subunit carries the thiolase activity.LCHAD deficiency is an autosomal recessive disorder. Patients usually present in infancy with recurrent attacks of hypoketotic hypoglycemia provoked by prolonged fasting, often during a minor intercurrent illness such as gastroenteritis (1). In addition, cardiomyopathy (1, 2) and hepatomegaly with cholestatic jaundice, which can sometimes progress to fulminant liver failure, are regularly observed (2, 3). Peripheral neuropathy and pigmentary retinopathy can occur during the course of the disease (2-5). LCHAD deficiency can also present as sudden infant death even in the neonatal period (2, 6).The diagn...