A study on the diagnosis and pathophysiology of carnitine deficiency

肉毒碱转运蛋白（OCTN 2基因的产物）的缺陷导致原发性肉毒碱缺乏症。首先，本研究调查了肉毒碱缺乏症中OCTN 2缺乏症的患病率和临床表现。酰基肉毒碱分析确定了269例肉毒碱缺乏症的2,694名受试者。2例为杂合突变，分别为S467 C/WT和V465 A/WT。这一结果表明，即使在OCTN 2突变的杂合子携带者中，感染或营养不良时的分解代谢状态也会引发代谢失代偿。第二，我们的研究建立了一种使用培养的皮肤成纤维细胞进行肉毒碱转运蛋白功能分析的方法。OCTN 2缺乏组细胞内肉毒碱/细胞外游离肉毒碱比值明显低于正常对照组。该方法还能够使用常规方法同时评价细胞内酰基肉碱谱以及细胞外酰基肉碱谱。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.