Two novel isovaleryl-CoA dehydrogenase gene mutations in a Chinese infant

• We report a case of Chinese infant with IVA.
• Two novel mutations are identified, c.39G > A (p.W13X) and c.597C > G (p.I199M).
• The mutation of p.I199M is predicted to destabilize the IVD monomer.
• p.I199M mutation may also affect the interaction between IVD and FAD.

Isovaleric acidemia (IVA) is a rare inherited metabolic disease caused by a deficiency in isovaleryl-CoA dehydrogenase (IVD). Newborn screening with tandem mass spectrometry leads to early identification of individuals with risk of IVA. The family specific mutations are useful for prenatal diagnosis. Molecular genetic analysis helps to further confirm the clinical diagnosis of IVA. We describe here the clinical and metabolic features of a Chinese infant with early onset IVA. Sequence analysis of the IVD gene identifies compound heterozygous mutations in this patient, c.39G > A (p.W13X) nonsense mutation and c.597C > G (p.I199M) missense mutation, both of which are previously unreported. Structural analyses suggest that the p.I199M missense mutation may destabilize the IVD monomer structure and affect the interaction between IVD and flavin adenine dinucleotide. Both the clinical and genetic features of this patient help to further expand our knowledge of IVA.