Carnitine-acylcarnitine translocase deficiency: metabolic consequences of an impaired mitochondrial carnitine cycle

We describe a patient with carnitine-acylcarnitine translocase deficiency ( MIM 212138), who presented with neonatal generalized seizures, heart failur e, and coma. Laboratory evaluation revealed hypoglycemia, hyperammonemia, l actic acidemia, hyperuricemia, and mild dicarboxylic aciduria. The fact tha t total plasma carnitine (7.1 mu mol/l [20-30]) and free carnitine (1.9 mu mol/l [12-18]) were low together with a high acylcarnitine/free carnitine r atio of 2.7 [0.4-1.0] prompted acylcarnitine analysis. This revealed the pr esence of large amounts of long-chain derivatives including C-16:0, C-16:1, C-18:1, C-18:2. Based on these findings carnitine-acylcarnitine translocas e deficiency was suspected which was confirmed by enzyme studies in fibrobl asts. The underlying complex metabolic consequences of this defect are revi ewed. Prenatal diagnosis was performed in a subsequent pregnancy and a defe ct ruled out by measurement of carnitine-acylcarnitine translocase activity in cultured chorionic villi cells. As the clinical recognition of a life-t hreatening fatty acid oxidation disorder may be difficult, defects in this pathway should be considered in any child with coma, an episode of a Reye-l ike syndrome, and cardiomyopathy. Since routine laboratory tests often do n ot provide clues about potential disorders and profiles of urinary organic acids may not be characteristic, we recommend to measure free carnitine and acylcarnitines in plasma in any child with hyperammonemia. hypo/hyperketot ic hypoglycemia or lactic acidemia for prompt treatment, proper genetic cou nseling, and potential prenatal diagnosis. (C) 2000 Elsevier Science B.V. A ll rights reserved.