Treem W R, Shoup M E, Hale D E, Bennett M J, Rinaldo P, Millington D S, Stanley C A, Riely C A, Hyams J S
Division of Pediatric Gastroenterology and Nutrition, Hartford Hospital, University of Connecticut School of Medicine, Farmington, USA.
Am J Gastroenterol. 1996 Nov;91(11):2293-300.
The similarity of the hepatic pathology in acute fatty liver of pregnancy (AFLP) to that seen in children with inherited disorders of intramitochondrial fatty acid oxidation (FAO) suggests that there may be a genetic basis for some cases of AFLP.
The purpose of this study was to examine patients with AFLP and their offspring to determine if there were women with AFLP who were heterozygous for the FAO defect, long chain 3-hydroxyacyl CoA dehydrogenase (LCHAD) deficiency.
We evaluated 12 women previously diagnosed with AFLP. Provocative fasting studies and skin biopsies for examination of their cultured skin fibroblasts were performed to search for a generalized defect in FAO both in vivo and in vitro. Cultured skin fibroblasts from AFLP patients, their children, and their husbands were also examined specifically for LCHAD activity.
Of 12 women with a previous episode of AFLP, eight had reduced LCHAD activity consistent with being heterozygous for LCHAD deficiency. The eight heterozygotes had a total of nine pregnancies complicated by AFLP. In seven of those nine pregnancies, the women developed severe preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Of the nine offspring delivered from these pregnancies, four were confirmed to be affected with homozygous LCHAD deficiency. Three other deceased infants were presumed to be LCHAD-deficient based on clinical findings, postmortem examination, and confirmed heterozygote parents. The remaining two infants delivered after pregnancies complicated by AFLP had LCHAD activity in the heterozygous range and are healthy at 18 and 24 months of age. Consistent with the known autosomal recessive nature of this defect, five tested husbands of LCHAD heterozygous women with a history of AFLP and affected infants also showed reduced LCHAD activity.
These studies indicate that a significant subgroup of women with AFLP are heterozygous for LCHAD deficiency and that careful observation of their offspring for signs of this disorder is warranted. Severe preeclampsia appears to increase the risk of AFLP in LCHAD heterozygous women.
妊娠急性脂肪肝（AFLP）的肝脏病理与线粒体脂肪酸氧化（FAO）遗传性疾病患儿的肝脏病理相似，提示部分AFLP病例可能存在遗传基础。
本研究旨在检查AFLP患者及其后代，以确定是否存在FAO缺陷（长链3-羟基酰基辅酶A脱氢酶（LCHAD）缺乏）的杂合子AFLP女性。
我们评估了12名先前诊断为AFLP的女性。进行激发性禁食研究和皮肤活检以检查其培养的皮肤成纤维细胞，以寻找体内和体外FAO的普遍缺陷。还专门检测了AFLP患者、其子女及其丈夫培养的皮肤成纤维细胞的LCHAD活性。
在12名曾患AFLP的女性中，8名LCHAD活性降低，符合LCHAD缺乏杂合子状态。这8名杂合子共有9次妊娠并发AFLP。在这9次妊娠中的7次，这些女性发生了严重先兆子痫和溶血、肝酶升高及血小板减少（HELLP）综合征。从这些妊娠中分娩的9名后代中，4名被确诊为纯合子LCHAD缺乏。另外3名死亡婴儿根据临床表现、尸检及确诊的杂合子父母推测为LCHAD缺乏。在并发AFLP的妊娠后分娩的其余2名婴儿LCHAD活性处于杂合子范围，在18个月和24个月时健康。与该缺陷已知的常染色体隐性性质一致，5名有AFLP病史且婴儿受影响的LCHAD杂合子女性的受试丈夫LCHAD活性也降低。
这些研究表明，相当一部分AFLP女性是LCHAD缺乏的杂合子，有必要仔细观察其后代是否有该疾病的迹象。严重先兆子痫似乎会增加LCHAD杂合子女性发生AFLP的风险。
