Genetics service, CHRU de Nancy - Brabois hospital, France.
INSERM, CRSA, Sorbonne Université, INSERM, CRSA, Paris, France, France.
Rev Esp Enferm Dig. 2019 Jan;111(1):76-79. doi: 10.17235/reed.2018.5828/2018.
Low phospholipid-associated cholelithiasis and intrahepatic cholestasis of pregnancy are two MDR3-related inherited liver disorders caused by biallelic or monoallelic ABCB4 loss-of-function variants. Low phospholipid-associated cholelithiasis is clinically characterized by the early onset of symptomatic cholelithiasis in young adults while intrahepatic cholestasis of pregnancy is a distinct clinical entity associated with adverse fetal outcomes. Of note, patients carrying ABCB4 sequence variations commonly exhibit phenotypic expression over a wide continuum due to environmental and hormonal contributing factors and genetic modifiers. Patients with an early diagnosis of MDR3-related diseases could benefit from ursodeoxycholic acid treatment in order to prevent acute and chronic complications as well as adverse pregnancy outcomes. We herein report five patients with an overlapping phenotype from low phospholipid-associated cholelithiasis to intrahepatic cholestasis of pregnancy, harboring five ABCB4 missense variants, four of which were novel. Our study highlights the phenotypic and genetic heterogeneity of inherited cholestatic liver diseases and also expands the mutation spectrum of ABCB4 sequence variations in adult cholestatic liver diseases.
低磷脂相关性胆石症和妊娠肝内胆汁淤积症是两种由 ABCB4 双等位基因突变或单等位基因突变引起的 MDR3 相关遗传性肝病。低磷脂相关性胆石症的临床特征是年轻成人中早发性有症状胆石症，而妊娠肝内胆汁淤积症是一种与不良胎儿结局相关的独特临床实体。值得注意的是，由于环境和激素因素以及遗传修饰因子的影响，携带 ABCB4 序列变异的患者通常表现出广泛的表型表达。早期诊断为 MDR3 相关疾病的患者可受益于熊去氧胆酸治疗，以预防急性和慢性并发症以及不良妊娠结局。我们在此报告了五例从低磷脂相关性胆石症到妊娠肝内胆汁淤积症的重叠表型患者，携带五个 ABCB4 错义变异，其中四个为新发现的变异。我们的研究强调了遗传性胆汁淤积性肝病的表型和遗传异质性，同时也扩展了成人胆汁淤积性肝病中 ABCB4 序列变异的突变谱。
