■异戊酸血症(IVA),以急性代谢危机和精神运动延迟为特征,是一种罕见的遗传性代谢疾病,由异戊酰辅酶A脱氢酶(IVD)缺乏引起。
■我们报告了一例中国IVA患者,该患者在天津市儿童医院住院并随访了8年。使用全外显子组测序和Sanger测序对患者及其父母进行遗传分析。我们在PubMed和Wanfang数据库中使用术语“异戊酸血症,“回顾相关文献,以获得临床和遗传特征的总结,并分析了基因型与表型的相关性。
■患者出现脑病症状,比如呕吐,嗜睡,和嗜睡。我们鉴定了IVD基因的复合杂合变体,包括未报告的变体c.224A>G(p。Asn75Ser)和报告的变体c.1195G>C(p。Asp399His)。给孩子开了低蛋白饮食,补充了L-肉碱。在为期8年的随访中,没有代谢紊乱或脑病症状复发。目前,儿童11岁,智力和运动表现正常。在25个相关参考文献中确定的另外154个病例与该病例合并,产生了155名患者的样本,包括52名无症状患者,64例新生儿发病,和39患有慢性间歇性疾病,发病年龄为1个月至10岁(中位年龄,2年)。在报道性的文章中,男女比例为1:1.06.主要症状包括呕吐,嗜睡,\"汗脚\"气味,喂养不良,发育迟缓,和癫痫。IVD蛋白123-159和356-403区域变异的比例在有症状患者中高于无症状患者。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.
■本病例报告描述了一个未报告的变体c.224A>G(p。Asn75Ser)的IVD基因,并总结了以前报告的病例。此外,分析IVA基因型与临床表型的相关性,以提高对本病的认识。
UNASSIGNED: 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).
UNASSIGNED: 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.
UNASSIGNED: The patient presented with encephalopathic symptoms, such as vomiting, lethargy, and somnolence. We identified compound heterozygous variants of the IVD 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.
UNASSIGNED: This
case report describes an unreported variant c.224A>G (p.Asn75Ser) of the IVD 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.