Nakazaki Kimitaka, Ogawa Erika, Ishige Mika, Ishige Nobuyuki, Fuchigami Tatsuo, Takahashi Shori
Department of Pediatrics and Child Health, Nihon University School of Medicine.
Tokyo Health Service Association.
Tohoku J Exp Med. 2018 Apr;244(4):279-282. doi: 10.1620/tjem.244.279.
Carnitine is a water-soluble amino acid derivative required for β-oxidation of long-chain fatty acids. In carnitine cycle abnormalities and low carnitine states, fatty acid β-oxidation is inhibited during fasting, resulting in hypoglycemia. Pivalic acid is a substance used in prodrugs to increase absorption of parent drugs, and antibiotics containing pivalic acid are frequently used as wide spectrum antibiotics for pediatric patients in Japan. Pivalic acid released after absorption is conjugated with free carnitine to form pivaloylcarnitine, which is then excreted in urine. As a consequence, long-term administration of pivalic acid containing antibiotics has been associated with depletion of free carnitine, inhibition of energy production and subsequent hypoglycemia. Here we report a case of a 23-month-old boy treated with an antibiotic containing pivalic acid for 3 days for upper respiratory tract infection. Laboratory data at referral indicated hypoglycemia, decreased free carnitine and elevated five-carbon acylcarnitine. Isomer separation confirmed the major component of increased five-carbon acylcarnitine to be pivaloylcarnitine, thereby excluding the possibility of a genetic metabolic disorder detected with similar acylcarnitine profile. The level of carnitine was normal when the antibiotic was not administered. Our case shows that the use of antibiotics containing pivalic acid in young children requires consideration of hypocarnitinemia, even with short-term administration.
肉碱是长链脂肪酸β氧化所需的水溶性氨基酸衍生物。在肉碱循环异常和低肉碱状态下，禁食期间脂肪酸β氧化受到抑制，导致低血糖。特戊酸是一种用于前体药物以增加母体药物吸收的物质，在日本，含特戊酸的抗生素经常被用作儿科患者的广谱抗生素。吸收后释放的特戊酸与游离肉碱结合形成特戊酰肉碱，然后随尿液排出。因此，长期使用含特戊酸的抗生素与游离肉碱耗竭、能量产生抑制及随后的低血糖有关。在此，我们报告一例23个月大男孩，因上呼吸道感染接受含特戊酸抗生素治疗3天。转诊时的实验室数据显示低血糖、游离肉碱降低和五碳酰基肉碱升高。异构体分离证实五碳酰基肉碱增加的主要成分是特戊酰肉碱，从而排除了通过类似酰基肉碱谱检测到的遗传代谢紊乱的可能性。未使用抗生素时肉碱水平正常。我们的病例表明，即使是短期使用，幼儿使用含特戊酸的抗生素也需要考虑低肉碱血症。
