Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle
Primary Carnitine Deficiency and Newborn Screening for Disorders of the Carnitine Cycle
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DOI：
10.1159/000448321
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发表时间：
2016-01-01
影响因子：
3.9
通讯作者：
Longo, Nicola
中科院分区：
文献类型：
--
作者：
Longo, Nicola
肉毒碱是长链脂肪酸穿过线粒体内膜进行随后的β-氧化所必需的。肉毒碱可以由身体合成，也可以通过食用肉类和乳制品在饮食中获得。肉毒碱转运缺陷，如由SLC 22 A5基因编码的OCTN 2转运蛋白活性缺陷引起的缺陷，导致原发性肉毒碱缺乏症，新生儿筛查计划可以在不可逆损伤之前识别出患有这种疾病的患者。最初的生化诊断可以通过分子检测确认，虽然直接研究成纤维细胞中的肉毒碱转运是非常有用的，以确认或排除原发性肉毒碱缺乏症的个体与未知的临床意义的遗传变异或谁继续有低水平的肉毒碱，尽管负分子分析。肉毒碱生物合成中的遗传缺陷通常不会导致血浆中肉毒碱水平降低。然而，三甲基赖氨酸羟化酶基因（肉毒碱生物合成中的关键基因）的缺失与非畸形型自闭症有关。因此，肉毒碱的新角色正在出现，与经典的先天性代谢缺陷无关。(C)2016 S. Karger AG，巴塞尔
Carnitine is needed for transfer of long-chain fatty acids across the inner mitochondrial membrane for subsequent beta-oxidation. Carnitine can be synthesized by the body and is also obtained in the diet through consumption of meat and dairy products. Defects in carnitine transport such as those caused by defective activity of the OCTN2 transporter encoded by the SLC22A5 gene result in primary carnitine deficiency, and newborn screening programmes can identify patients at risk for this condition before irreversible damage. Initial biochemical diagnosis can be confirmed through molecular testing, although direct study of carnitine transport in fibroblasts is very useful to confirm or exclude primary carnitine deficiency in individuals with genetic variations of unknown clinical significance or who continue to have low levels of carnitine despite negative molecular analyses. Genetic defects in carnitine biosynthesis do not generally result in low plasma levels of carnitine. However, deletion of the trimethyllysine hydroxylase gene, a key gene in carnitine biosynthesis, has been associated with non-dysmorphic autism. Thus, new roles for carnitine are emerging that are unrelated to classic inborn errors of metabolism. (C) 2016 S. Karger AG, Basel