A Rare Case of Isovaleric Acidemia With Hyperammonemia Caused by Compound Heterozygous IVD Variants: Clinical Features, Molecular Genetics, and Therapeutic Follow-Up.

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.