Retrospective analysis of isobutyryl CoA dehydrogenase deficiency.

Background: Isobutyryl-CoA dehydrogenase deficiency is a rare, autosomal recessive hereditary disease caused by a disorder in valine metabolism due to the deficiency of isobutyryl-CoA dehydrogenase. We provided two new mutations for ACAD8 and analyzed new sight to explore the association between the clinical phenotype and genotype of this disease.

Methods: The concentration of butyrylcarnitine was tested by tandem mass spectrometry. Butyryl carnitine and isobutyryl glycine levels were determined based on urine organic acid analysis. Gene mutations were analyzed through gene sequencing.

Results: Five individuals were diagnosed with isobutyryl-CoA dehydrogenase deficiency via newborn screening, and new mutations of ACAD8 encoding isobutyryl-CoA dehydrogenase were found. The mutations were c.1166G>A in exon 10 and c.986C>T in exon 9, which were analyzed as pathogenic sites. Both manifested as an increase in butyrylcarnitine and slightly elevated isobutyryl glycine levels. No abnormalities in growth and development were observed during follow-up. Additionally, we summarized 32 types of ACAD8 mutations reported worldwide, analyzed the distribution of mutations with clinical symptoms, and found them to be mainly concentrated in the N-terminal domain and C-terminal domain. These findings may provide new clues for the clinical diagnosis and management of isobutyryl-CoA dehydrogenase deficiency.

Conclusions: In this study, we reported new mutations of ACAD8 and performed a retrospective analysis of isobutyryl CoA dehydrogenase deficiency worldwide. Isobutyryl CoA dehydrogenase deficiency may pose a disease risk during the growth process, thereby requiring long-term follow-up.