ORIGINAL RESEARCH article
Front. Genet.
Sec. Genetics of Common and Rare Diseases
Volume 16 - 2025 | doi: 10.3389/fgene.2025.1584817
This article is part of the Research TopicBeyond Mutation: Exploring the Molecular Genetics and Pathomechanisms of Mendelian DisordersView all 3 articles
Very long-chain acyl-CoA dehydrogenase Deficiency Revisited: A Retrospective Genotype-Phenotype Analysis in a Saudi Tertiary Center
Provisionally accepted
- King Saud Medical City, Riyadh, Saudi Arabia
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In this retrospective study, we analyzed clinical, biochemical, and genetic data and examined correlations between prevalent variants and outcomes of very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Methods: Patients with VLCAD deficiency confirmed through molecular genetic testing at King Saud Medical City, Riyadh, Saudi Arabia, between 2016 and 2023 were included. Patients presented in the neonatal period with abnormal newborn screening and with metabolic decompensation and biochemical abnormalities clinically. Results: VLCAD deficiency was confirmed in 14 children. The mean age at presentation was 5.6 days. Clinically, 10 of the 14 patients presented with rhabdomyolysis. Hepatomegaly was observed in 9, cardiomyopathy in 7, and hypoglycemia in 7 patients. In total, 3 variants were detected in the 14 patients: c.1310A>C (p.Glu437Ala) in 2; c.134C>A(p.Ser45X) in 6; and c.65C>A (p.Ser22Ter) in 6 patients. Currently, 12 patients are alive, whereas 2 have died. No significant relationship was identified between genotype and survival (P = 0.719). Variant C.1310A was associated with an excellent prognosis. Unlike those in other studies, variants c.65C>A and c.134C>A were associated with poor outcomes and early presentation with metabolic decompensation. Discussion: Long-term, prospective studies integrating metabolic profiling, functional assays, and multi-omics approaches will be essential to unravel the complex interplay between genetic variants and clinical expression and prognostic outcomes in VLCAD deficiency.
Keywords: Clinical Characteristics, clinical, molecular, Saudi Arabia, VLCAD deficiency, genotype-phenotype correlation, Newborn screening
Received: 27 Feb 2025; Accepted: 12 May 2025.
Copyright: © 2025 Alhumaidi, Algaeed, Alkaff and Aladhadh. 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: Fahad Algaeed, King Saud Medical City, Riyadh, Saudi Arabia
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