AKR1D1和婴儿死亡率的变异:胆酸查是否应该成为新生儿查的常规部分?
Jade Hudson1, Stephanie Hyunh1, Bojana Rakic2
1Department of Medical Genetics and Provincial Medical Genetics Program, University of British Columbia and Women's Hospital of British Columbia, Vancouver, British Columbia, Canada.
由AKR1D1变体引起的先天性胆汁酸合成缺陷2型 (CBAS2),破坏胆汁酸的产生. 早期诊断和干预对于预防婴儿死亡等严重后果至关重要.
科学领域:
- 生物化学 生物化学
- 遗传学 是一个遗传学.
- 儿科 儿科 儿科
背景情况:
- 在AKR1D1中双性致病变体导致Δ4-3-oxosteroid 5β-reductase缺乏.
- 这种缺陷会破坏胆酸合成,导致先天胆酸合成缺陷2型 (CBAS2).
- 在婴儿期,CBAS2表现为胆固醇,凝血病和发育不良.
研究的目的:
- 报告一种带有意外婴儿死亡率的CBAS2病例.
- 突出诊断挑战和胆酸合成障碍的潜在致命结果.
- 倡导改进查策略,以早期检测CBAS2.
主要方法:
- 胆汁酸的死后生物化学分析.
- 基因检测用于识别AKR1D1变种.
- 一个患有肝功能障碍和脑内出血的婴儿的临床病例综述.
主要成果:
- 婴儿表现出几乎不存在的初级胆酸和累积的非典型胆酸中间体,与CBAS2一致.
- 已经确定了复合异构的AKR1D1变体 (NM_005989.3:c.[593C>T];[782G>A],p.
- 在8周的婴儿死亡与肝功能障碍和脑内出血有关.
结论:
- 胆酸合成障碍带来诊断挑战,如果不及早诊断和治疗,可能会导致致命的后果.
- 由于CBAS2的可治疗性质,早期诊断至关重要.
- 建议扩展新生儿查或快速向胆酸/胆固醇病的婴儿基因查.
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