Carnitine is an important component of the body’s energy metabolism. Carnitine helps the body turn fat into energy. Carnitine is made in the liver and kidney and is stored in the muscles, heart, brain, and sperm. Carnitine, like many substances, has different forms depending on the three-dimensional structure. It is designated based on orientation so that L-Carnitine (Levo or left) is the more important and active metabolic component that drives energy from fat.
Carnitine deficiency is a rare metabolic disorder that prevents the body from processing certain fats into energy, particularly during fasting (periods without food). Carnitine, a natural substance acquired mostly through food, carries fatty acids obtained through the diet to the mitochondria, the energy-producing centers in cells.1 Without carnitine, fatty acids cannot enter the mitochondria and be converted into energy. The buildup of fatty acids in cells may damage the liver, muscles, and heart.1
There are 2 types of Carnitine deficiency that exist. Primary carnitine deficiency is a genetic (inherited) disorder of the carnitine transporter system. Primary carnitine deficiency affects males and females in equal numbers,2 and strikes an estimated one in every 50,000 to one in every 100,000 newborns in the United States. It is more common in Japan, where the estimated incidence is one per 40,000 births.1,3 The signs and symptoms of carnitine deficiency typically appear during infancy or early childhood, especially in situations of dehydration or metabolic stress of an intercurrent illness, and can include encephalopathy (severe brain dysfunction), cardiomyopathy (a weakened and enlarged heart), confusion, vomiting, muscle weakness, and hypoglycemia (low blood sugar).1
The disease may be caused by a mutation (defect) in the SCL22A5 gene, which provides instructions for making a protein called OCTN2 that transports carnitine into cells; this form of the disorder is called primary carnitine deficiency. Muscle carnitine deficiency (restricted to muscle) is characterized by depletion of carnitine levels in muscle with normal serum concentrations. Evidence indicates that the causal factor is a defect in the muscle carnitine transporter.
When the disorder occurs as a complication of other metabolic diseases, it is known as secondary carnitine deficiency.1,2 Secondary deficiency is characterized by increased carnitine excretion in urine in the form of acyl-carnitine due to an accumulation of organic acids. Secondary carnitine deficiency can be caused by increased acylcarnitinie and carnitine urinary losses, treatment with certain medicines, a number of inherited metabolic disorders, poor diet or malabsorption of carnitine, from increased renal tubular loss of free carnitine (Fanconi syndrome), haemodialysis, peritoneal dialysis, or the increased excretion of acylcarnitines with certain drugs. There have been reported at least 15 syndromes in which carnitine deficiency seems to be secondary to genetic defects of intermediary metabolism or to other conditions.4 Patients with secondary carnitine deficiency accumulate organic acids which causes enhanced urinary excretion of carnitine in the form of acyl-carnitines.
In disorders of fatty acid oxidation, excessive lipid accumulation occurs in muscle, heart, and liver, with cardiac and skeletal myopathy and hepatomegaly. Long-chain acylcarnitines are also toxic and may have an arrhythmogenic effect, causing sudden cardiac death.
Encephalopathy may be caused by the decreased availability of ketone bodies associated with hypoglycemia. Preterm newborns also may be at risk for developing carnitine deficiency because immature renal tubular function combined with impaired carnitine biosynthesis renders them strictly dependent on exogenous supplies to maintain normal plasma carnitine levels.
Secondary carnitine deficiencies may occur due to certain disorders (such as chronic renal failure- or kidney failure as it is known) or under particular conditions (e.g., use of certain antibiotics) that reduce carnitine absorption or increase its elimination through the bowels. In particular, carnitine losses are excessive during all forms of hemodialysis and result in chronic carnitine deficiency.
