该MMACHC变异c.158T>C:在cblC患者中轻微的临床和生化表型和显著的可胺反应
Tanguy Demaret1, Karine Bédard2, Jean-François Soucy3
1Medical Genetics Division, Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine, Université de Montréal, Montréal, Québec, Canada; Centre de Génétique Humaine, Institut de Pathologie et Génétique, Gosselies, Belgium.
患有复合MMACHC突变的哥巴胺C疾病 (cblC) 患者表现出较轻微的症状,并对氧哥巴胺单一治疗反应良好. 相比之下,对c.271dupA突变的同胞细胞呈现严重的表型和生化异常,表明明显的疾病进展.
科学领域:
- 生物化学 生物化学
- 遗传学 遗传学是一种遗传学.
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 科巴胺C疾病 (cblC) 是最常见的维生素B12代谢遗传性疾病,由MMACHC突变引起.
- cblC导致甲基可巴胺和腺可巴胺缺乏,其特征是甲基氨酸 (MMA) 和血总同氨酸 (tHcy) 的升高.
研究的目的:
- 为了比较不同MMACHC突变组合的cblC患者的临床和生化表型.
- 为了评估对c.271dupA突变的化合物异构细胞与同构细胞单一治疗的治疗反应.
主要方法:
- 七名cblC患者的医疗记录的回顾性审查.
- 将患者分为复合型异胞 (c.158T>C/c.271dupA) 和同胞 (c.271dupA/c.271dupA) 的类别.
- 对临床结果,生化标志物 (MMA,tHcy) 和患者纤维细胞中的体外可巴胺吸收的分析.
主要成果:
- 复合类异构体表现出较温和的精神运动性能和正常的眼科发现与可胺单一治疗.
- 尽管进行了全面的五分疗法,但同类动物表现出严重的精神运动迟缓,视网膜病变和食问题.
- 生物化学标志物 (MMA,tHcy) 在同位素中显著较高,并且与治疗不同,与化合物不同,没有正常化.
结论:
- MMACHC突变的基因型显著影响cblC的临床严重程度和生物化学特征.
- 氧巴胺单体疗法有效地改善了复合异构菌的症状.
- 同胞性c.271dupA突变导致一种严重的cblC表型,该表型对标准疗法具有抗性.
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