Liu Xingmiao, Liu Xinquan, Fan Wenxuan, Zhang Zhongbin, Zhang Peiyuan, Liu Xiaojun, Lei Meifang, Li Qing, Yu Xiaoli, Li Dong
Department of Pediatric Neurology, Tianjin Children's Hospital/Tianjin University Children's Hospital, Tianjin, China.
School of Precision Instrument and Optoelectronics Engineering, Tianjin University, Tianjin, China.
Front Neurol. 2022 Jul 28;13:928334. doi: 10.3389/fneur.2022.928334. eCollection 2022.
Isovaleric acidaemia (IVA), characterized by an acute metabolic crisis and psychomotor delay, is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD).
We report the case of a Chinese patient with IVA who was admitted to Tianjin Children's Hospital and followed up for 8 years. Genetic analysis of the patient and his parents was conducted using the whole-exome sequencing and Sanger sequencing. We searched for similar reported cases in the PubMed and Wanfang databases using the term "isovaleric acidaemia," reviewed the related literature to obtain a summary of the clinical and genetic characteristics, and analyzed the genotype-phenotype correlations.
The patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. We identified compound heterozygous variants of the gene, including the unreported variant c.224A>G (p.Asn75Ser) and the reported variant c.1195G>C (p.Asp399His). The child was prescribed a low-protein diet supplemented with L-carnitine. During the 8-year follow-up, no metabolic disorder or encephalopathic symptoms recurred. At present, the child is 11 years of age and has normal mental and motor performance. Another 154 cases identified in 25 relevant references were combined with this case, resulting in a sample of 155 patients, including 52 asymptomatic patients, 64 with neonatal onset, and 39 with the chronic intermittent disease with onset from ages of 1 month to 10 years (median age, 2 years). Among articles that reported sex, the male-to-female ratio was 1:1.06. The cardinal symptoms included vomiting, lethargy, "sweaty foot" odor, poor feeding, developmental delay, and epilepsy. The proportion of variants in regions 123-159 and 356-403 of the IVD protein was greater in symptomatic patients than in asymptomatic patients. Conversely, in asymptomatic patients, the proportion of variants in the 282-318 region was greater than in symptomatic patients.
This case report describes an unreported variant c.224A>G (p.Asn75Ser) of the gene, and summarizes previously reported cases. Furthermore, the correlation between the genotype and clinical phenotype of IVA is analyzed to improve the understanding of this disease.
异戊酸血症（IVA）以急性代谢危机和精神运动发育迟缓为特征，是一种由异戊酰辅酶A脱氢酶（IVD）缺乏引起的罕见遗传性代谢疾病。
我们报告了一名患IVA的中国患者的病例，该患者入住天津儿童医院并接受了8年随访。使用全外显子测序和桑格测序对患者及其父母进行了基因分析。我们在PubMed和万方数据库中使用术语“异戊酸血症”搜索了类似的报道病例，查阅了相关文献以获取临床和遗传特征的总结，并分析了基因型与表型的相关性。
该患者出现了脑病症状，如呕吐、嗜睡和昏睡。我们鉴定出该基因的复合杂合变异，包括未报道的变异c.224A>G（p.Asn75Ser）和已报道的变异c.1195G>C（p.Asp399His）。给该患儿开了低蛋白饮食并补充左旋肉碱。在8年的随访期间，未再出现代谢紊乱或脑病症状。目前，该患儿11岁，精神和运动表现正常。将25篇相关参考文献中鉴定出的另外154例病例与本病例相结合，得到了155例患者的样本，其中包括52例无症状患者、64例新生儿起病患者和39例慢性间歇性疾病患者，起病年龄为1个月至10岁（中位年龄2岁）。在报告性别的文章中，男女比例为1:1.06。主要症状包括呕吐、嗜睡、“汗脚”气味、喂养困难、发育迟缓及癫痫。有症状患者中IVD蛋白123 - 159和356 - 403区域的变异比例高于无症状患者。相反，在无症状患者中，282 - 318区域的变异比例高于有症状患者。
本病例报告描述了该基因一个未报道的变异c.224A>G（p.Asn75Ser），并总结了先前报道的病例。此外，分析了IVA的基因型与临床表型之间的相关性，以增进对该疾病的了解。
