一例钠牛磺胆酸共转运多肽缺陷病患儿临床和遗传学分析

钠牛磺胆酸共转运多肽（NTCP）缺陷病是SLC10A1基因变异引起的遗传性胆汁酸代谢病。本研究报道一例NTCP缺陷病患儿的临床及遗传学特征。患儿，男，因皮肤巩膜黄染3月余就诊。查体皮肤及巩膜中度黄染，肝脏肿大；转氨酶、总胆汁酸及胆红素升高，以结合胆红素升高为主，伴25-OH-VitD水平降低；肝组织病理示肝细胞气球样变，部分肝细胞内淤胆，肝小叶结构破坏，汇管区炎性细胞浸润。予醋酸泼尼松抗炎，以及护肝和补充脂溶性维生素等治疗，转氨酶和胆红素等逐渐恢复正常，但胆汁酸水平仍高。17.2月龄时行SLC10A1基因分析，发现患儿为c.800C > T（p.Ser267Phe）突变的纯合子，其父母均为该变异携带者，确诊NTCP缺陷病。现已随访至34.3月龄，患儿体格及神经行为发育正常，黄疸消退，肝脏大小、质地和肝功能均恢复正常，但胆汁酸仍高。

Clinical and genetic analysis of a pediatric patient with sodium taurocholate cotransporting polypeptide deficiency

Sodium taurocholate cotransporting polypeptide (NTCP) deficiency is an inborn error of bile acid metabolism caused by mutations of SLC10A1 gene. This paper reports the clinical and genetic features of a patient with this disease. A 3.3-month-old male infant was referred to the hospital with the complaint of jaundiced skin and sclera over 3 months. Physical examination revealed moderate jaundice of the skin and sclera. The liver was palpable 3.5 cm below the right subcostal margin with a medium texture. Serum biochemistry analysis revealed markedly elevated bilirubin (predominantly direct bilirubin) and total bile acids (TBA), as well as decreased 25-OH-VitD level. On pathological analysis of the biopsied liver tissue, hepatocyte ballooning and cholestatic multinucleate giant cells were noted. The lobular architecture was distorted. Infiltration of inflammatory cells, predominantly lymphocytes, was seen in the portal tracts. In response to the anti-inflammatory and liver protective drugs as well as fat-soluble vitamins over 2 months, the bilirubin and transaminases levels were improved markedly while the TBA kept elevated. Because of persisting hypercholanemia on the follow-up, SLC10A1 gene analysis was performed at his age of 17.2 months. The child proved to be a homozygote of the reportedly pathogenic variant c.800C > T (p. Ser267Phe), while the parents were both carriers. NTCP deficiency was thus diagnosed. The infant was followed up until 34.3 months old. He developed well in terms of the anthropometric indices and neurobehavioral milestones. The jaundice disappeared completely. The liver size, texture and function indices all recovered. However, the hypercholanemia persisted, and the long-term outcome needs to be observed.