Li Huizhong, Shao Fang, Zhou Wei
Neonatal Disease Screening Center, The Affiliated Xuzhou Maternity and Child Health Care Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Mol Genet Metab Rep. 2024 May 3;39:101088. doi: 10.1016/j.ymgmr.2024.101088. eCollection 2024 Jun.
Isovaleric acidemia (IVA) is a rare autosomal recessive disorder that manifests as a deficiency of isovaleryl-CoA dehydrogenase (IVD), a key enzyme in leucine metabolism. The clinical presentations associated with IVD deficiency are variable and include feeding intolerance, vomiting, metabolic acidosis, ketonemia, "sweaty feet" odor, lethargy, coma and even death. Tandem mass spectrometry (MS/MS) and gas chromatography-mass spectrometry (GC/MS) methods were used to perform organic acid analysis of blood and urine samples from IVA patients, and the genetic analysis included next generation sequencing (NGS) and Sanger sequencing of the gene. Here, we report the case of an almost seven-year-old male patient from a Chinese family who was asymptomatic during the newborn period, including the clinical manifestations and examination results. Genetic analysis revealed a previously unreported compound heterozygous variant in the gene: c.593G > C (p.W198S) and c.859C > T (p.R287W).
异戊酸血症（IVA）是一种罕见的常染色体隐性疾病，表现为异戊酰辅酶A脱氢酶（IVD）缺乏，IVD是亮氨酸代谢中的关键酶。与IVD缺乏相关的临床表现多种多样，包括喂养不耐受、呕吐、代谢性酸中毒、酮血症、“汗脚”气味、嗜睡、昏迷甚至死亡。采用串联质谱（MS/MS）和气相色谱-质谱（GC/MS）方法对IVA患者的血液和尿液样本进行有机酸分析，基因分析包括该基因的下一代测序（NGS）和桑格测序。在此，我们报告了一名来自中国家庭的近七岁男性患者的病例，该患者在新生儿期无症状，包括临床表现和检查结果。基因分析揭示了该基因中一个此前未报告的复合杂合变异：c.593G>C（p.W198S）和c.859C>T（p.R287W）。
