Liver disease in pregnancy and fetal fatty acid oxidation defects

Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzymes, and low platelets (the HELLP syndrome) are serious disorders of the third trimester with high maternal and perinatal morbidity and mortality. Over the past decade, several clinical observations have demonstrated an association between these maternal syndromes and a recessively inherited fatty acid oxidation disorder, long chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. Many women who carried LCHAD-deficient fetuses developed maternal liver disease. Over the past few years, we and others have made significant progress in understanding the molecular basis for this fetal-maternal interaction. Here, we review the studies in literature that led to the establishment of this causative association with particular emphasis on the molecular analysis that delineated the molecular basis of this association. The likely mechanisms for the genotype-phenotype correlations in pediatric LCHAD deficiency and the fetal-maternal interaction are discussed. Finally, the potential implications of our current knowledge for families with pediatric LCHAD deficiency and for women who develop AFLP and HELLP syndrome are discussed.