Carnitine Palmitoyltransferase 2 Deficiency: The Time-Course of Blood and Urinary Acylcarnitine Levels during Initial L-Carnitine Supplementation
Carnitine Palmitoyltransferase 2 Deficiency: The Time-Course of Blood and Urinary Acylcarnitine Levels during Initial L-Carnitine Supplementation
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DOI：
10.1620/tjem.221.191
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发表时间：
2010-07-01
影响因子：
2.2
通讯作者：
Kondo, Naomi
中科院分区：
文献类型：
--
作者：
Hori, Tomohiro;Fukao, Toshiyuki;Kondo, Naomi
肉毒碱棕榈酰转移酶2（CPT 2）缺陷是最常见的线粒体β-氧化缺陷之一。一名患有婴儿型CPT 2缺乏症的女性患者，首次表现为Reye样综合征伴低血糖惊厥。由于血清游离肉碱水平非常低（低于10 μ mol/L），表明继发性肉碱缺乏，因此给予口服L-肉碱补充剂。她的血清和尿酰基肉毒碱配置文件进行了分析，连续评估时间过程中的L-肉毒碱补充的影响。在前两天的L-肉碱补充后，血清中游离肉碱的水平升高，然而，血清中的酰基肉碱水平和尿中游离肉碱和酰基肉碱的排泄量仍然很低。在第5天检测到血清游离肉毒碱水平的峰值，随后在第7天检测到乙酰肉毒碱的峰值，并且在第9天检测到长链酰基肉毒碱如016、C18、C18：1和018：2肉毒碱的峰值。此后游离肉毒碱再次成为主导。血清水平的这些峰分别对应于游离肉毒碱、乙酰肉毒碱和中链二羧酸肉毒碱的尿排泄峰。口服L-肉毒碱几天后才能增加血清肉毒碱水平，这可能是因为细胞内储存耗尽。此后，给药增加了异常酰基肉毒碱的排泄，其中一些已经在组织内积累。在第13天，中链二羧酸肉碱的排泄显著减少，表明组织酰基肉碱积累的改善。补充L-肉碱后血液和尿液酰基肉碱水平的这些时程变化支持补充L-肉碱对CPT 2缺乏患者的有效性。
Carnitine palmitoyltransferase 2 (CPT2) deficiency is one of the most common mitochondrial beta-oxidation defects. A female patient with an infantile form of CPT2 deficiency first presented as having a Reye-like syndrome with hypoglycemic convulsions. Oral L-carnitine supplementation was administered since serum free carnitine level was very low (less than 10 mu mol/L), indicating secondary carnitine deficiency. Her serum and urinary acylcarnitine profiles were analyzed successively to evaluate time-course effects of L-carnitine supplementation. After the first two days of L-carnitine supplementation, the serum level of free carnitine was elevated; however, the serum levels of acylcarnitines and the urinary excretion of both free carnitine and acylcarnitines remained low. A peak of the serum free carnitine level was detected on day 5, followed by a peak of acetylcarnitine on day 7, and peaks of long-chain acylcarnitines, such as 016, C18, C18:1 and 018:2 carnitines, on day 9. Thereafter free carnitine became predominant again. These peaks of the serum levels corresponded to urinary excretion peaks of free carnitine, acetylcarnitine, and medium-chain dicarboxylic carnitines, respectively. It took several days for oral L-carnitine administration to increase the serum carnitine levels, probably because the intracellular stores were depleted. Thereafter, the administration increased the excretion of abnormal acylcarnitines, some of which had accumulated within the tissues. The excretion of medium-chain dicarboxylic carnitines dramatically decreased on day 13, suggesting improvement of tissue acylcarnitine accumulation. These time-course changes in blood and urinary acylcarnitine levels after L-carnitine supplementation support the effectiveness of L-carnitine supplementation to CPT2-deficient patients.