Abstract:

Objective To explore the clinical features, gene variation and follow-up results of children with isovaleric acidemia (IVA), and to provide evidence for early recognition, diagnosis and treatment of IVA. Methods The clinical data of children diagnosed with IVA in the Department of Pediatric Endocrinology from April 2012 to October 2023 were retrospectively analyzed. Results Of the 34 children with IVA (22 boys and 12 girls), 15 had acute neonatal type, 3 had chronic intermittent type, and 16 had asymptomatic type confirmed by neonatal screening. Compared with asymptomatic group, blood isovalerylcarnitine (C5) level, C5/ acetylcarnitine (C2) ratio, C5/ propionylcarnitine (C3) ratio and urine isovalerylglycine level in the group with clinical symptoms (including acute neonatal type and chronic intermittent type) were significantly increased, with statistical significance (P<0.05). A total of 40 mutations were identified in 34 patients, most of which were missense mutations (30/40, 75.0%) and c.1208A>G (n=8) was the most frequent variant. There was no significant correlation between clinical manifestation and type of gene variation. Four patients, all of whom belonged to the acute neonatal type, died during follow-up. Thirty surviving children had considerably lower urinary isovalerylglycine levels at the most recent follow-up, with a statistically significant difference from before therapy (P<0.05). Conclusions Clinical manifestations of IVA lack specificity. Elevated C5, C5/C2 ratio and C5/C3 ratio in plasm and isovalerylglycine in urine are typical hallmarks of IVA. Newborn screening is pivotal for early diagnosis, treatment, and prognosis.

Key words: isovaleric academia, IVD gene, tandem mass spectrometry, newborn screening