ALDH5A1基因突变致琥珀酸半醛脱氢酶缺陷症1例报告并文献复习

Succinic semialdehyde dehydrogenase deficiency caused by ALDH5A1 gene mutation: a case report and literature review

目的探讨ALDH5A1基因突变致琥珀酸半醛脱氢酶缺陷症(SSADHD)的临床特征,基因突变及致病机制。方法回顾分析1例SSADHD患儿的临床资料和基因测序结果,并复习相关文献。结果患儿,女,3岁6个月,表现为反复发作的发作性肌张力障碍。头颅磁共振成像、视频脑电图、血液生化检查、血尿遗传代谢筛查均无异常。基因测序显示,ALDH5A1基因外显子区域有2处杂合突变,c.112G>A(p.A38T)(致病性尚不明确)、c.1529C>T(p.S510F)(已报道的致病突变);2处杂合突变分别来自其父母,为复合杂合突变,符合常染色体隐性遗传规律。确诊为ALDH5A1突变致SSADHD。检索到相关文献26篇,报道75种ALDH5A1突变,分别位于外显子1~11,涉及错义突变、缺失突变、插入突变、剪切突变和无义突变。结论 ALDH5A1基因突变与SSADHD发生密切相关,基因检测有助SSADHD确诊。

Objective To explore the clinical characteristics, gene mutation and pathogenesis of succinic semialdehyde dehydrogenase deficiency(SSADHD) caused by ALDH5 A1 gene mutation. Method The clinical data and gene sequencing results of SSADHD in a child were retrospectively analyzed, and the related literature was reviewed. Results A 3-year-and 6-month-old girl presented with recurrent episodes of paroxysmal dystonia. However, the brain magnetic resonance imaging, video electroencephalogram, blood biochemical examination and hematuria genetic metabolism screening all found no abnormalities. Gene sequencing showed that there were two heterozygous mutations in the exon region of ALDH5 A1 gene, c.112 G > A(p.A38 T)(pathogenicity is not yet clear) and c.1529 C > T(p.S510 F)(reported pathogenic mutation). The two heterozygous mutations were derived from their parents respectively, which were complex heterozygous mutations and consistent with autosomal recessive inheritance. Therefore, the child was diagnosed with SSADHD caused by ALDH5 A1 gene mutation. A total of 26 related literatures were retrieved, and 75 ALDH5 A1 gene mutations located in Exon1~Exon11 were reported, including missense mutations, deletion mutations, insertion mutations, splicing mutations and nonsense mutations. Conclusion ALDH5 A1 gene mutation is closely related to SSADHD, and gene detection is helpful for the diagnosis of SSADHD.