进行性家族性肝内胆汁淤积症1型1例临床特点和ATP8B1基因突变分析

进行性家族性肝内胆汁淤积症1型 （PFIC1） 是一种ATP8B1基因突变导致的以进行性胆汁淤积为主要临床表现的常染色体隐性遗传病。该文报道1例经ATP8B1突变分析证实的PFIC1患儿临床和遗传学特征。患儿为1岁2个月的男孩，因发现皮肤黄染10月余就诊。发病后先后在多家医院诊治，病因不详，疗效不佳。体查发现皮肤巩膜黄染，肝右肋下4cm，剑突下2cm，脾左肋下2cm可触及。肝功能检查发现血清胆汁酸、胆红素、转氨酶等均升高，而γ-谷氨酰转肽酶水平未见异常。诊断为遗传性胆汁淤积症，但病因不明。1岁8个月时经胆囊结肠Roux-en-Y吻合术，之后患儿黄疸迅速消退。5岁1个月时经全基因组测序及Sanger测序验证，发现患儿为ATP8B1基因突变c.2081T > A （p.I694N） 的纯合子，最终确诊为PFIC1。电话随访至6岁，黄疸未再反复，但远期预后有待观察。

Clinical feature and ATP8B1 mutation analysis of a patient with progressive familial intrahepatic cholestasis type I

Progressive familial intrahepatic cholestasis type I (PFIC1) is an autosomal recessive disorder caused by biallelic mutations of ATP8B1 gene, with progressive cholestasis as the main clinical manifestation. This paper reports the clinical and genetic features of a PFIC1 patient deifnitely diagnosed by ATP8B1 genetic analysis. The patient, a boy aged 14 months, was referred to the hospital with the complaint of jaundiced skin and sclera over 10 months. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. On physical examination, hepatosplenomegaly was discovered in addition to jaundice of the skin and sclera. The liver was palpable 4 cm below the right subcostal margin and 2 cm below the xiphoid while the spleen 2 cm below the left subcostal margin. The liver function test revealed elevated levels of serum total bile acids, bilirubin, and transaminases;however, the γ-glutamyl transferase level was normal. The diagnosis was genetic cholestasis of undetermined origin. At the age of 1 year and 8 months, a Roux-en-Y cholecystocolonic bypass operation was performed, and thereafter the jaundice disappeared. At 5 years and 1 month, via whole genome sequencing analysis and Sanger sequencing conifrmation, the boy was found to be a homozygote of mutation c.2081T>A(p.I694N) of ATP8B1 gene, and thus PFIC1 was deifnitely diagnosed. The boy was followed up until he was 6 years, and jaundice did not recur, but the long-term outcome remains to be observed.