Heterozygosity for the common LCHAD mutation (1528G > C) is not a major cause of HELLP syndrome and the prevalence of the mutation in the Dutch population is low

Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an autosom al recessive disorder of mitochondrial fatty acid oxidation. Apart from lif e-threatening metabolic derangement with hypoketotic hypoglycemia, patients often show liver disease, cardiomyopathy, and neuropathy. A common mutatio n (1528G>C) in the gene coding for the cr-subunit of the mitochondrial trif unctional protein harboring LCHAD activity is found in 87% of the alleles o f patients, LCHAD is considered a rare disorder with only 63 patients repor ted 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 aspec ific symptomatology is not clear. A remarkable association between LCHAD de ficiency and the hemolysis, elevated liver enzymes, and low platelets (HELL P) 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 mut ation 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 hi story of HELLP syndrome, the prevalence of the common LCHAD mutation was al so low (1:113). We conclude that LCHAD deficiency ist indeed, a rare disord er and that heterozygosity for the common mutation is not a major cause of the HELLP syndrome.