Alhumaidi Suzan Suliman, Algaeed Fahad Abdulrahman, Aladhadh Meshari Fayez, Alkaff Sara Abdulrahman
Genetics and Metabolic Department, King Saud Medical City, Riyadh, Saudi Arabia.
Front Genet. 2025 May 30;16:1584817. doi: 10.3389/fgene.2025.1584817. eCollection 2025.
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.
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.
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 seven patients. In total, three 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 six patients. Currently, 12 patients are alive, whereas two have died. No significant relationship was identified between genotype and survival ( = 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.
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.
在这项回顾性研究中，我们分析了临床、生化和基因数据，并研究了常见变异与极长链酰基辅酶A脱氢酶（VLCAD）缺乏症结局之间的相关性。
纳入2016年至2023年期间在沙特阿拉伯利雅得国王沙特医疗城通过分子基因检测确诊为VLCAD缺乏症的患者。患者在新生儿期因新生儿筛查异常以及临床上出现代谢失代偿和生化异常而就诊。
14名儿童确诊为VLCAD缺乏症。就诊时的平均年龄为5.6天。临床上，14名患者中有10名出现横纹肌溶解。9名患者出现肝肿大，7名出现心肌病，7名出现低血糖。14名患者共检测到三种变异：2名患者为c.1310A>C（p.Glu437Ala）；6名患者为c.134C>A（p.Ser45X）；6名患者为c.65C>A（p.Ser22Ter）。目前，12名患者存活，2名患者死亡。未发现基因型与生存之间存在显著关系（P = 0.719）。变异C.1310A与良好预后相关。与其他研究不同，变异c.65C>A和c.134C>A与不良结局和代谢失代偿的早期表现相关。
整合代谢谱分析、功能测定和多组学方法的长期前瞻性研究对于阐明VLCAD缺乏症中基因变异与临床表达及预后结局之间的复杂相互作用至关重要。
