Clinical characteristics and genetic analysis of isobutyryl CoA dehydrogenase deficiency in Xuzhou:population screening results / 中国新生儿科杂志

ABSTRACT

Objective:To study the clinical features and genetic characteristics of isobutyryl-CoA dehydrogenase deficiency (IBDD) of neonates in Xuzhou area.Methods:From October 2016 to October 2021, neonates diagnosed with IBDD using tandem mass spectrometry in Xuzhou area were retrospectively studied. Their clinical phenotypes and genotypes, clinical diagnosis, treatment and follow-up were analyzed.Results:A total of 510 057 neonates were screened and 10 cases of IBDD were diagnosed. The 10 IBDD cases showed increased butyryl carnitine (C4), C4/C2 and C4/C3 during screening and follow-up tests. One case had transient elevated transaminase and one case showed delayed language development. The other 8 cases were otherwise normal. A total of 16 mutation loci of acyl-CoA dehydrogenase 8 (ACAD8) gene were found, including 10 unreported loci c.567+8C>T, c.213G>T, c.553C>T, c.1190T>C, c.1060G>A, c.494G>A, c.771C>A, c.962A>T, c.715A>G and c.731G>A. Genetic mutations were found in Exon 3, Exon 4, Exon 5, Intron 5, Exon 7, Exon 9 and Exon 10. The hot spots of mutations were c.1176G>T, c. 286G>A and c.1000C>T.Conclusions:IBDD is a rare disease without specific clinical manifestations. Neonatal metabolic disease screening combined with urinary organic acid tests and genetic sequencing can be used for early detection and diagnosis of IBDD. No serious adverse outcome is found in IBDD patients during short-term follow-up, however, long-term follow-up is recommended.