Newborn screening for isovaleric acidemia: A case report of a Chinese patient with novel variants

Abstract

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 IVD 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 IVD gene: c.593G > C (p.W198S) and c.859C > T (p.R287W).