ACUTE FATTY LIVER OF PREGNANCY, HEMOLYSIS, ELEVATED LIVER-ENZYMES, AND LOW PLATELETS SYNDROME, AND LONG-CHAIN 3-HYDROXYACYL-COENZYME-A DEHYDROGENASE-DEFICIENCY

Background: The similarity of the hepatic pathology in acute fatty liv er of pregnancy (AFLP) to that seen in children with inherited disorde rs of intramitochondrial fatty acid oxidation (FAG) suggests that ther e may be a genetic basis for some cases of AFLP. Objective: The purpos e of this study was to examine patients with AFLP and their offspring to determine if there were women with AFLP who were heterozygous for t he FAO defect, long chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) defi ciency. Methods: We evaluated 12 women previously diagnosed with AFLP. Provocative fasting studies and skin biopsies for examination of thei r cultured skin fibroblasts were performed to search for a generalized defect in FAO both in vivo and in vitro. Cultured skin fibroblasts fr om AFLP patients, their children, and their husbands were also examine d specifically for LCHAD activity. Results: Of 12 women with a previou s episode of AFLP, eight had reduced LCHAD activity consistent with be ing heterozygous for LCHAD deficiency. The eight heterozygotes had a t otal of nine pregnancies complicated by AFLP. In seven of those nine p regnancies, the women developed severe preeclampsia and hemolysis, ele vated liver enzymes, and low platelets (HELLP) syndrome. Of the nine o ffspring delivered from these pregnancies, four were confirmed to be a ffected with homozygous LCHAD deficiency. Three other deceased infants were presumed to be LCHAD-deficient based on clinical findings, postm ortem examination, and confirmed heterozygote parents. The remaining t wo infants delivered after pregnancies complicated by AFLP had LCHAD a ctivity in the heterozygous range and are healthy at 18 and 24 months of age. Consistent with the known autosomal recessive nature of this d efect, five tested husbands of LCHAD heterozygous women with a history of AFLP and affected infants also showed reduced LCHAD activity. Conc lusions: These studies indicate that a significant subgroup of women w ith AFLP are heterozygous for LCHAD deficiency and that careful observ ation of their offspring for signs of this disorder is warranted. Seve re preeclampsia appears to increase the risk of AFLP in LCHAD heterozy gous women.