Liver disease in pregnancy and fetal fatty acid oxidation defects

Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevat ed liver enzymes, and low platelets (the HELLP syndrome) are serious disord ers of the third trimester with high maternal and perinatal morbidity and m ortality. Over the past decade, several clinical observations have demonstr ated an association between these maternal syndromes and a recessively inhe rited fatty acid oxidation disorder, long chain 3-hydroxyacyl-CoA dehydroge nase (LCHAD) deficiency. Many women who carried LCHAD-deficient fetuses dev eloped maternal liver disease. Over the past few years, we and others have made significant progress in understanding the molecular basis for this fet al-maternal interaction. Here, we review the studies in literature that led to the establishment of this causative association with particular emphasi s on the molecular analysis that delineated the molecular basis of this ass ociation. 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 s yndrome are discussed. (C) 2000 Academic Press.