[Screening and clinical analysis of isovaleric acidemia newborn in Zhejiang province].

Objective: To investigate the incidence,clinical,biochemical and genetic characteristics of isovaleric acidemia (IVA) in Zhejiang province.

Methods: Between January 2009 and December 2019, a total of 3 510 004 newborns were screened for IVA using tandem mass spectrometry. Patients of IVA were confirmed by urine organic acid and gene detection. IVA patients were given diet and life management, supplemented with L-carnitine and glycine treatment, long-term followed up to observe and evaluate the growth and intellectual development.

Results: A total of 15 patients with IVA were diagnosed, with an incidence of 1/234 000. Three patients had acute neonatal IVA, and the rest were asymptomatic. The isovalerylcarnitine (C5) levels were increased in all patients. Twelve children underwent urinary organic acid analysis, of which 11 cases had elevated isovalerylglycine levels, 4 cases with 3-hydroxyisovalerate increased simultaneously. Eleven IVA patients underwent genetic testing, 9 patients were compound heterozygous variants in gene, one with homozygous variants in gene, and one harbored one variant. Nineteen variants (14 missense mutations, 3 intron mutations, 1 code shift mutation, and 1 synonymous mutation) were identified, 11 of which were not reported. Among the 15 IVA patients, one patient died and two patients were followed up locally. The remaining patients had no obvious clinical symptoms during the follow-up (2-79 months). Three patients presented with growth and development delay, the remaining had normal physical and mental development.

Conclusions: The clinical manifestations of IVA are non-specific, and the gene spectrum is scattered. Newborn patients screened by tandem mass spectrometry can receive early diagnosis and treatment, so as to correct metabolic defects and pathophysiological changes.