A Rare Case of Isovaleric Acidemia With Hyperammonemia Caused by Compound Heterozygous <scp> <i>IVD</i> </scp> Variants: Clinical Features, Molecular Genetics, and Therapeutic Follow‐Up

ABSTRACT To improve understanding of isovaleric acidemia (IVA) by analyzing the clinical features, genetic basis, and treatment outcomes of a child with chronic intermittent IVA. A 4‐month‐old infant presenting with lethargy, pallor, and growth retardation was diagnosed with IVA using tandem mass spectrometry (MS/MS), urinary organic acid analysis, and genetic testing. MS/MS and urine gas chromatography–mass spectrometry revealed elevated isovalerylcarnitine and isovalerylglycine. Whole‐exome sequencing identified a novel homozygous IVD gene variant (c.899_905delinsCCCACAG) in the proband, with both parents confirmed as carriers. The patient was treated with a leucine‐restricted diet, glycine, L‐carnitine, and arginine. Follow‐up showed reduced metabolite levels and improved neurodevelopment. IVA is an autosomal recessive disorder caused by isovaleryl‐CoA dehydrogenase deficiency, leading to toxic metabolite accumulation. Clinical symptoms are nonspecific, often resulting in misdiagnosis. Early use of MS/MS and genetic testing enables timely diagnosis and targeted treatment, improving outcomes.