1例Dubin-Johnson综合征婴儿的临床特征及ABCC2基因型研究

Dubin-Johnson综合征（DJS）是ABCC2基因变异引起的常染色体隐性遗传病，以长期或间歇性结合胆红素升高为主要临床表现。该文报道1例DJS患儿的临床特征和ABCC2变异特点。患儿为9.5月龄男婴，因发现肝功能异常9个月就诊，主要临床表现为新生儿期起病的黄疸，多次血生化检查均显示血清总胆红素、结合胆红素、总胆汁酸明显升高，先后在多家医院诊治，病因不明，疗效不佳。体格检查：皮肤巩膜黄染，肝右肋下3 cm可及，质中，脾不大。遗传学分析显示患儿ABCC2基因存在c.3988-2A > T和c.3825C > G（p.Y1275X）两个致病性变异，分别来源于母亲和父亲，其中c.3988-2A > T为未报道的新剪接位点变异，从而确诊为DJS。给予熊去氧胆酸和苯巴比妥口服治疗半月，黄疸消退，生化指标改善，但远期预后有待随访观察。文献复习发现，DJS新生儿/婴儿患者主要临床表现为生后不久出现的胆汁淤积性黄疸，其ABCC2基因变异存在明显异质性。

Clinical features and ABCC2 genotypic analysis of an infant with Dubin-Johnson syndrome

Dubin-Johnson syndrome (DJS) is an autosomal recessive disorder resulting from biallelic mutations of ABCC2 gene, with long-term or intermittent conjugated hyperbilirubinemia being the main clinical manifestation. This paper aims to report the clinical features and ABCC2 genotypes of an infant with DJS. A 9.5-month-old male infant was referred to the hospital due to abnormal liver function discovered over 9 months. The major clinical presentation was prolonged jaundice since neonatal period. A series of biochemistry analysis revealed markedly elevated total bilirubin, conjugated bilirubin and total bile acids. The patient had been managed in different hospitals, but the therapeutic effects were unsatisfactory due to undetermined etiology. Physical examination revealed jaundiced skin and sclera, and a palpable liver 3 cm below the right subcostal margin with medium texture. The spleen was not enlarged. Genetic analysis revealed a splice-site variant c.3988-2A > T and a nonsense variant c.3825C > G (p.Y1275X) in the ABCC2 gene of the infant, which were inherited from his mother and father respectively. The former had not been previously reported. Then ursodeoxycholic acid and phenobarbital were given orally. Half a month later, as a result, his jaundice disappeared and the biochemistry indices improved. However, the long-term outcome needs to be observed. Literature review revealed that neonates/infants with DJS presented with cholestatic jaundice soon after birth as the major clinical feature, and the ABCC2 variants exhibited marked heterogeneity.