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ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1532902
Novel ACAD8 Variants Identified in Isobutyryl-CoA Dehydrogenase Deficiency: Challenges in Phenotypic Variability and Management
Provisionally accepted- Changzhi Maternal and Child Care Hospital, Changzhi, China
Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive disorder caused by biallelic variants in the ACAD8 gene, which disrupts valine metabolism. In this study, we report seven individuals identified through newborn screening (NBS) with elevated C4-acylcarnitine levels, including five confirmed patients and two heterozygous carriers. Genetic analysis identified 12 distinct ACAD8 variants, seven of which were novel (c.221C>T, c.518T>C, c.727A>G, c.868G>A, c.947A>T, c.966G>A, c.1058T>C). According to ACMG classification criteria, c.221C>T was classified as likely pathogenic, while the remaining variants were categorized as variants of uncertain significance (VUS). During a mean follow-up of 4.81 years, all patients maintained normal growth patterns but two patients developed neurological symptoms that included recurrent febrile seizures and sensory integration dysfunction. These findings expand the ACAD8 variant spectrum, highlight the phenotypic variability of IBDD, and underscore the importance of long-term followup and individualized management strategies.
Keywords: ACAD8 gene, Isobutyryl-CoA dehydrogenase deficiency, Newborn screening, Next-generation sequencing, Novel variant
Received: 22 Nov 2024; Accepted: 31 Mar 2025.
Copyright: © 2025 Tao, Han, Li, Li, Hao, Song, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Yilun Tao, Changzhi Maternal and Child Care Hospital, Changzhi, China
Xiaoze Li, Changzhi Maternal and Child Care Hospital, Changzhi, China
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