Tohoku J. Exp. Med., 2010, 221(3)

Carnitine Palmitoyltransferase 2 Deficiency: The Time-Course of Blood and Urinary Acylcarnitine Levels during Initial L-Carnitine Supplementation

TOMOHIRO HORI,¹ TOSHIYUKI FUKAO,^1,2,3 HIRONORI KOBAYASHI,⁴ TAKAHIDE TERAMOTO,¹ MASAKI TAKAYANAGI,⁵ YUKI HASEGAWA,⁴ TETSUHIKO YASUNO,⁶ SEIJI YAMAGUCHI⁴ and NAOMI KONDO¹

¹Department of Pediatrics, Gifu University Graduate School of Medicine, Gifu, Japan
²Medical Information Science Division, United Graduate School of Drug Discovery and Medical Information, Gifu University, Gifu, Japan
³Clinical Research Division, Nagara Medical Center, Gifu, Japan
⁴Department of Pediatrics, Shimane University School of Medicine, Shimane, Japan
⁵Department of Metabolism, Chiba Children's Hospital, Chiba, Japan
⁶Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University School of Medicine, Fukuoka, Japan

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 μmol/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 C16, C18, C18:1 and C18:2 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.

keywords —— carnitine palmitoyltransferase 2; CPT2; L-carnitine; acylcarnitine profile; carnitine administration

© 2010 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2010, 221, 191-195

Correspondence; Toshiyuki Fukao, M.D., Ph.D., Department of Pediatrics, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 501-1194, Japan.

e-mail:toshi-gif@umin.net