Yang Zi, Yamada Jennifer, Zhao Yiwen, Strauss Arnold W, Ibdah Jamal A
Division of Gastroenterology, Wake Forest University School of Medicine, Medical Center Blvd, Winston-Salem, NC 27157, USA.
JAMA. 2002 Nov 6;288(17):2163-6. doi: 10.1001/jama.288.17.2163.
Acute fatty liver of pregnancy (AFLP) and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome are serious complications of pregnancy. Studies in families with recessively inherited mitochondrial trifunctional protein defects documented an association between these maternal illnesses and fetal deficiency of long-chain 3-hydroxyacyl coenzyme A dehydrogenase; this enzyme resides in the alpha subunit of the trifunctional protein and catalyzes the third step in long-chain fatty acid beta oxidation.
To estimate the frequency of fetal long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency in pregnancies complicated by AFLP or HELLP syndrome.
DESIGN, SETTING, AND SUBJECTS: Cohort study in which 108 consecutive blood samples from women who developed AFLP or HELLP syndrome, from their offspring, or from their partners were referred to our laboratory for molecular screening from January 1997 to December 2001. Twenty-seven women had AFLP and 81 had HELLP syndrome. We screened the DNA for mutations in the alpha subunit of the trifunctional protein.
Presence of mutations that cause 3-hydroxyacyl coenzyme A dehydrogenase deficiency in the offspring.
We detected mutations causing pediatric long-chain 3-hydroxyacyl coenzyme A dehydrogenase deficiency in 5 families (19%) with maternal history of AFLP (95% confidence interval, 9%-54%). The maternal allele carried a prevalent glutamic acid 474 to glutamine (E474Q) mutation. The paternal allele carried the E474Q mutation in 3 families and a stop codon mutation in the other 2 families. Only 1 woman with HELLP syndrome was heterozygous for the E474Q mutation; no mutations were detected in the newborn.
The association between AFLP and the E474Q mutation in the fetus is significant. Screening newborns for this mutation in pregnancies complicated by AFLP could allow early diagnosis and treatment in newborns and genetic counseling and prenatal diagnosis in subsequent pregnancies in affected families.
妊娠急性脂肪肝（AFLP）和溶血、肝酶升高及血小板减少（HELLP）综合征是妊娠的严重并发症。对隐性遗传的线粒体三功能蛋白缺陷家族的研究表明，这些母体疾病与胎儿长链3-羟基酰基辅酶A脱氢酶缺乏之间存在关联；该酶存在于三功能蛋白的α亚基中，催化长链脂肪酸β氧化的第三步。
评估妊娠合并AFLP或HELLP综合征时胎儿长链3-羟基酰基辅酶A脱氢酶缺乏的发生率。
设计、地点和研究对象：队列研究，1997年1月至2001年12月期间，将108份来自患AFLP或HELLP综合征的女性、其后代或其配偶的连续血样送至我们实验室进行分子筛查。27名女性患有AFLP，81名患有HELLP综合征。我们对三功能蛋白α亚基的DNA进行突变筛查。
后代中导致3-羟基酰基辅酶A脱氢酶缺乏的突变的存在情况。
我们在5个有AFLP母亲病史的家族（19%）中检测到导致小儿长链3-羟基酰基辅酶A脱氢酶缺乏的突变（95%置信区间，9%-54%）。母体等位基因携带常见的谷氨酸474突变为谷氨酰胺（E474Q）突变。父体等位基因在3个家族中携带E474Q突变，在另外2个家族中携带终止密码子突变。只有1名患有HELLP综合征的女性为E474Q突变的杂合子；新生儿未检测到突变。
AFLP与胎儿E474Q突变之间的关联显著。对妊娠合并AFLP的新生儿进行该突变筛查，可实现新生儿的早期诊断和治疗，以及对受影响家庭后续妊娠的遗传咨询和产前诊断。
