Get access

Disorders of carnitine transport and the carnitine cycle


  • Nicola Longo,

    Corresponding author
    • Division of Medical Genetics, Department of Pediatrics, University of Utah, 2C412 SOM, 50 North Medical Drive, Salt Lake City UT 84132.
    Search for more papers by this author
    • Nicola Longo is Professor of Pediatrics and Director of the Metabolic Service at the University of Utah. His research covers inherited disorders of fatty acid oxidation and the development of new therapies for metabolic disorders.

  • Cristina Amat di San Filippo,

    Search for more papers by this author
    • Cristina Amat di San Filippo is a Research Associate working on the molecular bases of primary carnitine deficiency.

  • Marzia Pasquali

    Search for more papers by this author
    • Marzia Pasquali is Associate Professor of Pathology at the University of Utah in Salt Lake City and Medical Director of the Biochemical Genetics and Newborn Screening at ARUP Laboratories. She has a strong interest in the development of new testing for the diagnosis of inborn errors of metabolism.

  • How to cite this article: Longo N, di San Filippo CA, Pasquali M. 2006. Disorders of carnitine transport and the carnitine cycle. Am J Med Genet Part C Semin Med Genet 142C:77–85.


Carnitine plays an essential role in the transfer of long-chain fatty acids across the inner mitochondrial membrane. This transfer requires enzymes and transporters that accumulate carnitine within the cell (OCTN2 carnitine transporter), conjugate it with long chain fatty acids (carnitine palmitoyl transferase 1, CPT1), transfer the acylcarnitine across the inner plasma membrane (carnitine-acylcarnitine translocase, CACT), and conjugate the fatty acid back to Coenzyme A for subsequent beta oxidation (carnitine palmitoyl transferase 2, CPT2). Deficiency of the OCTN2 carnitine transporter causes primary carnitine deficiency, characterized by increased losses of carnitine in the urine and decreased carnitine accumulation in tissues. Patients can present with hypoketotic hypoglycemia and hepatic encephalopathy, or with skeletal and cardiac myopathy. This disease responds to carnitine supplementation. Defects in the liver isoform of CPT1 present with recurrent attacks of fasting hypoketotic hypoglycemia. The heart and the muscle, which express a genetically distinct form of CPT1, are usually unaffected. These patients can have elevated levels of plasma carnitine. CACT deficiency presents in most cases in the neonatal period with hypoglycemia, hyperammonemia, and cardiomyopathy with arrhythmia leading to cardiac arrest. Plasma carnitine levels are extremely low. Deficiency of CPT2 present more frequently in adults with rhabdomyolysis triggered by prolonged exercise. More severe variants of CPT2 deficiency present in the neonatal period similarly to CACT deficiency associated or not with multiple congenital anomalies. Treatment for deficiency of CPT1, CPT2, and CACT consists in a low-fat diet supplemented with medium chain triglycerides that can be metabolized by mitochondria independently from carnitine, carnitine supplements, and avoidance of fasting and sustained exercise. © 2006 Wiley-Liss, Inc.