Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel; Institute of Human Genetics, Galilee Medical Center, Nahariya, Israel.
Movement Disorders Institute, Department of Neurology, Chaim Sheba Medical Center, Ramat Gan, Israel; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
Genet Med. 2024 May;26(5):101086. doi: 10.1016/j.gim.2024.101086. Epub 2024 Jan 27.
Cerebrotendinous xanthomatosis (CTX) is a rare, autosomal recessive bile acid synthesis disorder. Biallelic pathogenic variants in CYP27A1, encoding for sterol 27-hydroxylase, impair cholic acid (CA) and chenodeoxycholic acid (CDCA) synthesis and lead to accumulation of cholestanol and C bile alcohols. Treatment with CDCA decreases the accumulation of these harmful metabolites and slows disease progression. Currently, CDCA is contraindicated for use during pregnancy based on animal studies that showed that high-dose CDCA may cause fetal harm when administered to pregnant animals. Data regarding the safety of CDCA treatment in humans are lacking.
We present a case series of 19 pregnancies in 9 women with CTX who either received CDCA treatment throughout pregnancy or did not.
In 11 pregnancies where mothers continued CDCA treatment, no complications were reported, and newborns were born at or near full term, with normal birth weight and Apgar scores. In 8 pregnancies where mothers did not receive CDCA, 2 newborns experienced elevated bilirubin soon after birth. One woman who stopped treatment during her pregnancy deteriorated neurologically while off treatment.
The data we present support the benefit of continued CDCA treatment in pregnant women with CTX for both the affected women and their offspring.
脑腱性黄瘤病（CTX）是一种罕见的常染色体隐性胆汁酸合成障碍。编码甾醇 27-羟化酶的 CYP27A1 的双等位基因致病性变异会损害胆酸（CA）和鹅脱氧胆酸（CDCA）的合成，导致植物固醇和 C 型胆汁醇的积累。用 CDCA 治疗可减少这些有害代谢物的积累，并减缓疾病进展。目前，根据动物研究，CDCA 在妊娠期间被禁用，因为高剂量的 CDCA 给妊娠动物用药时可能会造成胎儿伤害。缺乏关于人类 CDCA 治疗安全性的数据。
我们报告了 9 名 CTX 女性的 19 例妊娠病例系列，这些女性在妊娠期间要么接受了 CDCA 治疗，要么未接受治疗。
在 11 例母亲继续接受 CDCA 治疗的妊娠中，没有报告并发症，新生儿足月或接近足月出生，体重和阿普加评分正常。在 8 例母亲未接受 CDCA 治疗的妊娠中，有 2 例新生儿出生后胆红素升高。一名在妊娠期间停止治疗的女性在停药期间神经功能恶化。
我们提供的数据支持 CTX 孕妇继续接受 CDCA 治疗的益处，这对受影响的女性及其后代都有益处。
