Department of Pediatrics, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.
Department of Pediatrics, Fukui Prefectural Hospital, Fukui, Japan.
Pediatr Res. 2022 Nov;92(5):1391-1399. doi: 10.1038/s41390-022-01979-z. Epub 2022 Feb 8.
The clinical severity of very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is difficult to predict using conventional diagnostic methods.
Peripheral blood mononuclear cells obtained from 14 VLCAD deficiency patients and 23 healthy adults were loaded with carbon-13-universally labeled (U-C-) fatty acids. Differences in acylcarnitine ratios between the patients and healthy groups and correlations between acylcarnitine ratios and a newly established clinical severity score (CSS) in the patient group were statistically examined.
There was a significant decrease in the C-C2/C-C18 and C-C12/C-C14 ratios in the U-C-stearic acid loading test and in the C-C2/C-C18:1 and C-C12:1/C-C14:1 ratios in the U-C-oleic acid loading test in the patient group. The values of each ratio were significantly correlated with the CSS, suggesting that they could predict disease severity. Additionally, patients with a higher C-C16/C-C18 ratio than the C-C14/C-C18 ratio in the U-C-stearic acid loading test had a significantly higher CSS and were presumed to have more severe disease.
Our data indicated that this method could be used to predict the clinical severity of VLCAD deficiency, and identify patients at a risk of severe disease.
We established a novel method to predict the severity of VLCAD deficiency by performing a loading test with carbon-13-labeled fatty acids on peripheral blood mononuclear cells. The U-C-oleic acid loading test was useful for comparing the patient group with the control group in terms of disease severity. The U-C-stearic acid loading test was useful for identifying the more severely affected patients. These methods are relatively less invasive and enable rapid evaluation of the clinical severity.
使用常规诊断方法，很难预测极长链酰基辅酶 A 脱氢酶（VLCAD）缺乏症的临床严重程度。
从 14 例 VLCAD 缺乏症患者和 23 例健康成年人中提取外周血单核细胞，并用碳-13 标记的（U-C-）脂肪酸加载。统计分析患者组与健康组之间酰基肉碱比值的差异，以及患者组中酰基肉碱比值与新建立的临床严重程度评分（CSS）之间的相关性。
在 U-C-硬脂酸加载试验中，患者组的 C-C2/C-C18 和 C-C12/C-C14 比值显著降低，在 U-C-油酸加载试验中，C-C2/C-C18:1 和 C-C12:1/C-C14:1 比值显著降低。每个比值均与 CSS 显著相关，提示其可预测疾病严重程度。此外，在 U-C-硬脂酸加载试验中，患者的 C-C16/C-C18 比值高于 C-C14/C-C18 比值，其 CSS 显著更高，提示疾病更严重。
我们的数据表明，该方法可用于预测 VLCAD 缺乏症的临床严重程度，并识别出患有严重疾病风险的患者。
我们建立了一种新的方法，通过对外周血单核细胞进行碳-13 标记脂肪酸加载试验来预测 VLCAD 缺乏症的严重程度。U-C-油酸加载试验有助于比较患者组和对照组之间的疾病严重程度。U-C-硬脂酸加载试验有助于识别病情较重的患者。这些方法相对侵袭性较小，能够快速评估临床严重程度。
