Disorders of carnitine biosynthesis and transport

作者：El Hattab Ayman W; Scaglia Fernando^*

来源：Molecular Genetics and Metabolism, 2015, 116(3): 107-112.

DOI：10.1016/j.ymgme.2015.09.004

• Systemic carnitine deficiency
• Carnitine transport defect
• Autism spectrum disorders
• Cardiomyopathy
• Fatty acid oxidation

Carnitine is a hydrophilic quaternary amine that plays a number of essential roles in metabolism with the main function being the transport of long-chain fatty acids from the cytosol to the mitochondrial matrix for beta-oxidation. Camitine can be endogenously synthesized. However, only a small fraction of camitine is obtained endogenously while the majority is obtained from diet, mainly animal products. Carnitine is not metabolized and is excreted in urine. Carnitine homeostasis is regulated by efficient renal reabsorption that maintains camitine levels within the normal range despite variabilities in dietary intake. Diseases occurring due to primary defects in camitine metabolism and homeostasis are comprised in two groups: disorders of carnitine biosynthesis and carnitine transport defect. While the hallmark of carnitine transport defect is profound carnitine depletion, disorders of carnitine biosynthesis do not cause carnitine deficiency due to the fact that both carnitine obtained from diet and efficient renal camitine reabsorption can maintain normal carnitine levels with the absence of endogenously synthesized carnitine. Camitine transport defect phenotype encompasses a broad clinical spectrum including metabolic decompensation in infancy, cardiomyopathy in childhood, fatigability in adulthood, or absence of symptoms. The phenotypes associated with the camitine transport defect result from the unavailability of enough carnitine to perform its functions particularly in fatty acid beta-oxidation. Camitine biosynthetic defects have been recently described and the phenotypic consequences of these defects are still emerging. Although these defects do not result in camitine deficiency, they still could be associated with pathological phenotypes due to excess or deficiency of intermediate metabolites in the carnitine biosynthetic pathway and potential carnitine deficiency in early stages of life when brain and other organs develop. In addition to these two groups of primary carnitine defects, several metabolic diseases and medical conditions can result in excessive carnitine loss leading to a secondary camitine deficiency.

• 出版日期2015-11