Objective: 3-Hydroxyisobutyryl-CoA hydrolase (HIBCH) deficiency is a rare metabolic disease of valine metabolism. Only 22 cases of HIBCH deficiency have been reported in the literature. Our algorithm could help in the diagnosis of this disease. Methods: HIBCH gene analysis was performed in all cases. Results: The common features of our five patients from the same family with a developmental delay, seizures, and neurological regression were the elevation of 3-hydroxy-isobutyryl-carnitine and Leigh-like abnormalities. Unlike other patients in the literature, our patients were diagnosed with HIBCH gene analysis, rather than whole exome sequencing (WES). In all our cases, a missense c.452C>T, p. Ser151Leu homozygous novel pathogenic mutation was detected in the HIBCH gene. Conclusion: In cases where HIBCH deficiency is considered in our differential diagnosis algorithm, HIBCH gene analysis, which is cost-effective, should be performed instead of WES, and the number of cases should be increased in the literature.


中文翻译：

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仅通过 HIBCH 基因分析和新的致病突变诊断出的 3-羟基异丁酰辅酶 A 水解酶 (HIBCH) 缺乏病例


目的： 3-羟基异丁酰辅酶A水解酶（HIBCH）缺乏症是一种罕见的缬氨酸代谢性疾病。文献中仅报道了 22 例 HIBCH 缺乏症。我们的算法可以帮助诊断这种疾病。方法：对所有病例进行HIBCH基因分析。结果：我们来自同一家庭的 5 名患有发育迟缓、癫痫发作和神经功能退化的患者的共同特征是 3-羟基-异丁酰基-肉碱和 Leigh 样异常升高。与文献中的其他患者不同，我们的患者被诊断为 HIBCH 基因分析，而不是全外显子组测序 (WES)。在我们所有的案例中，错义 c.452C>T，p。在HIBCH基因中检测到Ser151Leu纯合新的致病突变。结论：在我们的鉴别诊断算法中考虑HIBCH缺陷的情况下，应进行具有成本效益的HIBCH基因分析而不是WES，并应增加文献中的病例数。