先天性胆汁酸合成障碍2型一家系临床和遗传学分析:两个AKR1D1新突变的识别

发布时间：2018-07-20 17:11

【摘要】：先天性胆汁酸合成障碍2型(CBAS2)是编码Δ4-3-氧固醇5β-还原酶的AKR1D1基因突变导致的常染色体隐性遗传病,以胆汁淤积性黄疸为主要临床表现,伴脂肪和脂溶性维生素吸收障碍。本文报道了1例CBAS2患儿的临床特点及AKR1D1基因突变分析结果。患儿为8个月男婴,因发现全身皮肤、巩膜黄染7月余就诊。体查发现患儿发育、营养差;皮肤、巩膜轻度黄染;肝右肋下8 cm,质地中等,脾脏不大。血生化结果发现转氨酶和总胆红素升高,以结合胆红素升高为主,但γ-谷氨酰转肽酶和总胆汁酸水平基本正常。肝脏组织学检查见胆管排列紊乱,多核巨细胞易见,肝细胞内明显淤胆,伴间质纤维组织增生及淋巴细胞浸润。代谢性肝病组套二代测序及Sanger测序验证结果证实患儿AKR1D1基因型为c.579+2del T/c.853CT(p.Q285X),两个突变均为新突变,且分别来源于其母亲和父亲。患儿最终确诊为CBAS2,给予鹅去氧胆酸治疗后,肝功能明显好转,肝肿大逐渐改善。3个月后随访,肝脏右肋下2.5 cm可及,质软,肝功能各项指标已恢复正常。
[Abstract]:Congenital bile acid synthesis disorder type 2 (CBAS2) is an autosomal recessive hereditary disease caused by mutation of AKR1D1 gene encoding 螖 4-3-oxysteroid 5 尾 -reductase. The main clinical manifestation is cholestatic jaundice, accompanied by fat and fat soluble vitamin absorption disorder. This paper reports the clinical characteristics of a child with CBAS2 and the results of AKR1D1 gene mutation analysis. The child was a 8-month-old boy who was treated for 7 months with scleral yellow staining due to the discovery of his whole body skin. Body examination showed that the children developed and had poor nutrition; the skin was slightly yellow stained with sclera; the liver was 8 cm below the right costal texture and the spleen was not large. The results of blood biochemistry showed that transaminase and total bilirubin increased, but the levels of 纬 -glutamyl transpeptidase and total bile acid were normal. Liver histology showed that the bile duct was disarranged, the multinucleated giant cells were easy to be seen, the hepatocytes were obviously cholestatic, accompanied by interstitial fibrous tissue proliferation and lymphocytic infiltration. The results of second-generation sequencing and Sanger sequencing in metabolic liver disease group confirmed that the genotype of AKR1D1 was c. 579 2del T / c. 853 CT (p. Q285X). Both mutations were new and originated from their mothers and fathers, respectively. The children were diagnosed as CBAS2, the liver function was obviously improved and the hepatomegaly was gradually improved after the treatment of chenodeoxycholic acid. After 3 months follow-up, the liver was 2.5 cm below the right costal, soft in quality and normal in various indexes of liver function.
【作者单位】：暨南大学附属第一医院儿科;
【基金】：国家自然科学基金(81570793)
【分类号】：R725.9

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