A study on the diagnosis and pathophysiology of carnitine deficiency

OCTN2基因产物肉碱转运体的缺失会导致原发性肉碱缺乏症。首先，本研究调查了肉碱缺乏症患者中OCTN_2缺乏症的患病率和临床表现。酰肉碱分析在2694名受试者中发现了269例肉碱缺乏症。2例分别为S467C/WT和V465A/WT杂合突变。这一结果表明，感染或营养不良时的分解代谢状态即使在OCTN2突变的杂合子载体中也会引发代谢失调。第二，我们的研究建立了一种利用培养的皮肤成纤维细胞进行肉碱转运蛋白功能分析的方法。OCTN2缺乏症患者细胞内肉碱/细胞外游离肉碱比值明显低于正常对照组。该方法还可以使用常规方法同时评估细胞内和细胞外的酰卡尼汀图谱。这一策略有望进一步应用于脂肪酸氧化的功能分析。

Deficiency of carnitine transporter, a product of OCTN2 gene, causes a primary carnitine deficiency. First, this study surveyed the prevalence and clinical presentation of OCTN2 deficiency among the carnitine deficiency. Acylcarnitine analysis identified 269 cases of carnitine deficiency out of 2,694 subjects. Two cases had heterozygous mutation, S467C/WT and V465A/WT, respectively. This result suggests that catabolic state upon infection or poor nutrition can trigger metabolic decompensation even in the heterozygous carrier of OCTN2 mutation.Second, our study established a method for functional analysis of carnitine transporter using cultured skin fibroblast. The ratio of intracellular carnitine/extracellular free carnitine in OCTN2 deficiency was significantly lower than in normal controls. This method also enables to evaluate intracellular acylcarnitine profile simultaneously as well as extracellular acylcarnitine profile using conventional method. Further application of this strategy for the functional analysis of fatty acid oxidation is expected.