Analysis of four Chinese patients with neonatal–onset isovaleric acidemia

Objective To present the clinical and biochemical features, treatment, outcome and molecular findings of four Chinese patients with neonatal–onset isovaleric acidemia, and prenatal diagnosis of one case. Methods One boy and three girls with onset of isovaleric acidemia from the age of one to four days of life, who were diagnosed and followed–up at the Depantment of Pediatrics of Peking University First Hospital, were evaluated. Isovaleric acidemia was diagnosed by analysis of urinary organic acids, blood acylcarnitines and an isovaleryl–CoA dehydrogenase (IVD) gene study. Three survivors were treated with L–carnitine, glycine, low–leucine formula and a protein–restricted diet. Results Four patients were admitted at the age of 25 days to 4 years presented with recurrent vomiting, unconsciousness and coma. A characteristic smell of dirty socks and severe metabolic acidosis were noted. Three patients had leukopenia or pancytopenia and three had hyperammonemia. Highly elevated blood isovalerylcarnitine of 3.2 to 20.7 μmol/L (normal value A, c.1183C>T, c.1193G>A and c.1208A>G) had been reported and three mutations (c.145C>T, c.611A>G and c.676–677insA) were novel. Progressive improvement was observed in three patients after treatment. Two of the three patients were normal at four and 14 years old at follow–up and third one was three years old with mild psychomotor retardation at follow–up. One of the four cases was diagnosed by postmortem study whose mother underwent amniocentesis at the gestational age of 19 weeks during her second pregnancy for prenatal diagnosis. Organic acids in the amniotic fluid were normal. In cultured amniocytes, only one heterozygous mutation, c.158G>A, was found in the IVD gene. These results showed that the fetus was not affected by isovaleric acidemia. Postnatal urinary organic acids, blood acylcarnitines and IVD gene analysis of the cord blood cells confirmed the prenatal diagnosis. Conclusions For patients with onset isovaleric acidemia, appropriate dietary treatment and symptomatic treatment may lead to a good outcome. Amniotic fluid disease–specific metabolites and amniocyte gene analysis are reliable for the prenatal diagnosis of isovaleric acidemia. Key words: Isovaleric acidemia; IVD gene; Isovaleryl–CoA dehydrogenase; Organic aciduria; Prenatal diagnosis