Eight novel mutations detected from eight Chinese patients with isovaleric acidemia

Isovaleric acidemia (IVA), a rare autosomal recessive disorder in leucine metabolism caused by defected IVD gene, is characterized by episodes of acute metabolic crisis and psychomotor development retardation. This study aimed to determine the clinical, biochemical, and mutation spectrum of patients with IVA from mainland China. Eight patients (three boys and five girls) from eight unrelated families were collected, IVD gene mutations and phenotypes were examined. The patients were admitted because of vomiting, feeding difficulty, psychomotor retardation and “dirty sock” odor. Elevated blood isovaleryl (C5)-carnitine and urine isovalerylglycine were detected from all our patients. Fourteen mutations of the IVD gene were detected, eight of them are novel, c.145C>T (p.Q49Ter), c.359G>A (p.R120Q), c.424C>T (p.R142C), c.458T>C (p.L153P), c.466-1G>T, c.676_677insA (p.T226Nfs*13), c.1039G>A (p.A347T) and c.1076A>G (p.D359G). With this study, a total of 34 alleles were studied in the Chinese population. c.1208A>G (p.Y403C), the common mutation in Taiwan, accounts for 9/34 alleles (7 in previous reports and 2 in this study). We described eight novel mutations detected from eight unrelated Chinese patients and provided evidence to support that the p.Y403C is the hotspot mutation in this population. •Fifteen mutations of the IVD gene were identified from eight Chinese IVA patients.•Eight novel mutations were found.•The mutation p.Y403C is the hotspot mutation in the Han Chinese population.