Department of Neonatal Surgery, Anhui Provincial Children's Hospital (Anhui Hospital, Pediatric Hospital of Fudan University), Hefei, Anhui, China.
Medicine (Baltimore). 2024 Jan 26;103(4):e36991. doi: 10.1097/MD.0000000000036991.
Dubin-Johnson syndrome (DJS) is a rare autosomal recessive liver disorder, characterized by conjugated hyperbilirubinemia. This case report investigates the clinical characteristics and longitudinal outcomes of a neonate diagnosed with DJS.
A newborn presented with elevated bilirubin levels and abnormal liver enzyme readings. Comprehensive genetic evaluation was conducted, which included peripheral blood sample collection from the infant and both parents after obtaining informed consent and high-throughput trio exome sequencing was performed. The genetic analysis revealed 2 significant mutations in the ABCC2 gene on chromosome 10: the insertion mutation c.4237(exon30)_c.4238(exon30)ins CT, inherited from the father, and the missense mutation c.517(exon5)G > A, inherited from the mother. Both mutations were classified as pathogenic according to the ACMG 2015 guidelines, indicating a compound heterozygous inheritance pattern. The patient's treatment regimen included phototherapy, which was initiated to address her jaundice upon admission. To support liver function and regulate gut activity, oral ursodeoxycholic acid (20 mg/kg/dose, twice a day) and probiotics were administered. Additionally, a postdischarge medication plan involving a low-dose regimen of phenobarbital (3.5 mg/kg/dose, twice a day) was implemented for 2 weeks.
During a 2-year follow-up after discharge, the infant's bilirubin levels significantly decreased, and liver enzymes, including GGT, progressively normalized.
This case report enhances the understanding of DJS in neonates by emphasizing the clinical ramifications of compound heterozygous mutations within the ABCC2 gene and documenting the evolution of the disease. The gradual normalization of liver function tests suggests potential compensatory mechanisms in response to the genetic abnormalities in neonates with DJS. The correlation between the patient's genetic profile of compound heterozygosity and her milder clinical phenotype warrants attention, suggesting that this specific genetic configuration may be associated with less severe manifestations of the disease. The necessity for long-term follow-up is highlighted, recognizing that intercurrent stress conditions could influence the hepatic profile and potentially exacerbate symptoms. Such sustained observation is crucial to further delineate the genomic and clinical landscape of DJS, offering opportunities to refine prognostic and therapeutic approaches.
Dubin-Johnson 综合征（DJS）是一种罕见的常染色体隐性肝脏疾病，其特征为结合胆红素升高。本病例报告研究了一名诊断为 DJS 的新生儿的临床特征和纵向结局。
一名新生儿出现胆红素水平升高和肝功能酶学异常。在获得知情同意后，对婴儿及其父母进行外周血样本采集，并进行高通量三代外显子组测序。基因分析显示 10 号染色体 ABCC2 基因存在 2 个显著突变：从父亲遗传的 c.4237(exon30)_c.4238(exon30)ins CT 插入突变，以及从母亲遗传的 c.517(exon5)G>A 错义突变。根据 ACMG 2015 指南，这两种突变均被归类为致病性突变，表明为复合杂合遗传模式。该患者的治疗方案包括光疗，入院时因黄疸而开始进行光疗。为了支持肝功能和调节肠道活动，给予口服熊去氧胆酸（20mg/kg/剂量，每天两次）和益生菌。此外，还为患者制定了出院后药物治疗计划，包括使用低剂量苯巴比妥（3.5mg/kg/剂量，每天两次）治疗 2 周。
出院后 2 年的随访期间，患儿胆红素水平显著下降，包括 GGT 在内的肝功能酶逐渐恢复正常。
本病例报告通过强调 ABCC2 基因复合杂合突变的临床意义，并记录疾病的演变过程，加深了对新生儿 DJS 的认识。肝功能检查的逐渐正常化提示 DJS 新生儿可能存在对遗传异常的代偿机制。患者复合杂合状态的遗传特征与较轻微的临床表型之间的相关性值得关注，表明这种特定的遗传构象可能与疾病的较轻表现相关。强调需要进行长期随访，因为并发应激情况可能会影响肝脏状况并潜在加重症状。这种持续观察对于进一步描绘 DJS 的基因组和临床特征至关重要，为完善预后和治疗方法提供机会。
