Successful treatment of infantile oxysterol 7α-hydroxylase deficiency with oral chenodeoxycholic acid.
Successful treatment of infantile oxysterol 7α-hydroxylase deficiency with oral chenodeoxycholic acid.
复制标题
口服鹅去氧胆酸成功治疗婴儿氧化甾醇7α-羟化酶缺乏症
DOI：
10.1186/s12876-021-01749-x
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发表时间：
2021-04-13
影响因子：
2.4
通讯作者：
Wang JS
中科院分区：
文献类型：
--
作者：
Tang YP;Gong JY;Setchell KDR;Zhang W;Zhao J;Wang JS
CYP7B1 编码的氧化甾醇 7α-羟化酶缺乏与致命的婴儿进行性肝内胆汁淤积和遗传性痉挛性截瘫 5 型有关。大多数报道的婴儿期出现肝病的 CYP7B1 突变患者死于肝衰竭。然而，最近有报道称，两名接受鹅去氧胆酸治疗的患者幸存下来。 CYP7B1 缺陷的表型和基因型之间的相关性尚未明确确定。一名 5 个月零 7 天大的中国非近亲父母婴儿从 1 个月大起因进行性胆汁淤积和凝血酶原时间延长而被转诊。基因检测显示 CYP7B1 中存在复合杂合突变 c.187C > T(p.R63X)/c.334C > T(p.R112X)，尿胆汁酸的快原子轰击质谱分析证实存在非典型肝毒性 3β-羟基-Δ5-胆汁酸。在等待肝移植期间，她口服鹅去氧胆酸。她的肝功能迅速改善，尿液非典型胆汁酸恢复正常，直到 23 个月大时进行最后一次随访时，她的健康状况一直良好。她 15 岁的弟弟没有婴儿期胆汁淤积病史，但携带相同的 CYP7B1 突变，从 13 岁起就出现步态异常。神经系统检查发现下肢反射亢进和痉挛。脑部 MRI 显示双侧基底神经节和额顶叶白质的血管周围空间扩大。总之，这些发现强调，CYP7B1 缺乏症的表型差异很大，即使在兄弟姐妹中也是如此，早期给予鹅去氧胆酸可能会改善预后。
Deficiency of oxysterol 7α-hydroxylase, encoded by CYP7B1, is associated with fatal infantile progressive intrahepatic cholestasis and hereditary spastic paraplegia type 5. Most reported patients with CYP7B1 mutations presenting with liver disease in infancy have died of liver failure. However, it was recently reported that two patients treated with chenodeoxycholic acid survived. Correlations between the phenotype and genotype of CYP7B1 deficiency have not been clearly established. A 5-month-7-day-old Chinese baby from non-consanguineous parents was referred for progressive cholestasis and prolonged prothrombin time from one month of age. Genetic testing revealed compound heterozygous mutations c.187C > T(p.R63X)/c.334C > T(p.R112X) in CYP7B1, and fast atom bombardment mass spectrometry analysis of the urinary bile acid confirmed the presence of atypical hepatotoxic 3β-hydroxy-Δ5-bile acids. While awaiting liver transplantation she was orally administered chenodeoxycholic acid. Her liver function rapidly improved, urine atypical bile acids normalized, and she thrived well until the last follow-up at 23 months of age. Her 15-year-old brother, with no history of infantile cholestasis but harboring the same mutations in CYP7B1, had gait abnormality from 13 years of age. Neurological examination revealed hyper-reflexia and spasticity of the lower limbs. Brain MRI revealed enlarged perivascular space in the bilateral basal ganglia and white matter of frontal parietal. In summary, these findings highlight that the phenotype of CYP7B1 deficiency varies widely, even in siblings and that early administration of chenodeoxycholic acid may improve prognosis.