L-carnitine is a naturally occurring compound that plays a role in how the body generates energy. It transports long-chain fatty acids from the cell’s cytoplasm into the mitochondria, where they are converted into usable energy through a process called beta-oxidation. This process is important for tissues that rely heavily on fat for fuel, such as the skeletal muscles and the heart. A deficiency occurs when there is an insufficient amount of L-carnitine, preventing the proper transport of fatty acids and hindering energy production, which can lead to medical complications.
Causes and Types of L-Carnitine Deficiency
L-carnitine deficiency is categorized into two classifications based on its origin: primary and secondary. Primary carnitine deficiency (PCD) is an inherited genetic disorder resulting from a mutation in the SLC22A5 gene. This gene provides instructions for the OCTN2 protein, the transporter responsible for moving carnitine into cells, particularly in the kidneys, heart, and muscles. A defect in the OCTN2 transporter reduces carnitine uptake by tissues and leads to excessive loss through the kidneys, resulting in systemic depletion. Because it affects the cell’s ability to take in carnitine, it is considered the most severe type and often presents early in life. This inherited condition is passed down in an autosomal recessive pattern, meaning an individual must inherit a non-working copy of the gene from both parents.
Secondary carnitine deficiency is an acquired condition that develops due to an underlying medical issue or external factor. Chronic kidney disease, especially in patients undergoing hemodialysis, is a common cause, as dialysis can lead to carnitine loss from the blood. Liver disease can impair the body’s ability to synthesize carnitine, while malnutrition or malabsorption decrease the amount obtained from the diet.
Certain medications, such as the anti-seizure drug valproic acid, interfere with carnitine metabolism, increasing the risk of deficiency. Inborn errors of metabolism, like organic acidemias, can also cause carnitine to be used up to remove toxic byproducts. Since secondary deficiency is acquired, it can appear at any age and may be resolved by addressing the root cause.
Recognizing the Signs
The signs of L-carnitine deficiency primarily affect the skeletal muscles, heart, and liver, as these organs rely heavily on fatty acid metabolism for energy. Muscular manifestations are frequent, often presenting as generalized muscle weakness and fatigue, particularly noticeable during physical activity. Infants with the primary deficiency may exhibit hypotonia (decreased or floppy muscle tone), poor feeding, and failure to thrive.
In older children and adults, muscle weakness can be progressive, sometimes leading to exercise intolerance and myalgia (muscle pain). The heart muscle is highly susceptible to this energy deficit because it uses fatty acids as its main energy source. This can lead to cardiomyopathy, which is a weakening and enlargement of the heart muscle that can progress to heart failure.
Cardiac involvement can also manifest as rhythm disturbances, shortness of breath, or swelling. Metabolic and hepatic issues are significant signs, particularly in infants and young children. The inability to break down fat for energy during periods without food, such as fasting or illness, forces the body to rely solely on glucose, resulting in dangerously low blood sugar (hypoglycemia).
This hypoglycemia is often hypoketotic, meaning the body cannot produce backup energy molecules (ketones) from fat. Affected individuals may also experience an enlarged liver (hepatomegaly) as fatty acids accumulate in the tissue. These metabolic crises, often triggered by infection, can lead to severe lethargy, vomiting, and encephalopathy (a serious condition affecting brain function).
Diagnosis and Treatment
The diagnostic process begins with clinical suspicion based on characteristic signs, such as unexplained muscle weakness, cardiomyopathy, or episodes of hypoketotic hypoglycemia. Confirmation is achieved through biochemical testing, which involves measuring carnitine levels in the blood and urine. Clinicians specifically look at the concentrations of free carnitine and total carnitine; very low plasma free carnitine levels indicate a deficiency.
For primary carnitine deficiency, many cases are identified through newborn screening programs that test for low carnitine levels shortly after birth. Genetic testing can confirm the diagnosis by analyzing the SLC22A5 gene for mutations. For secondary deficiency, diagnostic efforts focus on identifying the underlying medical condition responsible for the depletion.
The standard therapeutic approach for L-carnitine deficiency is supplementation with L-carnitine, often called levocarnitine. This treatment aims to restore carnitine levels in the plasma and tissues, effectively alleviating many symptoms, particularly heart and muscle issues. Supplementation is typically administered orally, though intravenous administration may be necessary during acute metabolic crises or when oral intake is not possible.
Individuals with primary carnitine deficiency usually require lifelong supplementation, sometimes at high doses, to maintain normal levels. Management involves avoiding prolonged fasting and reducing the intake of high-fat foods, especially in cases related to fatty acid oxidation disorders. Addressing the root cause, such as adjusting medication or managing kidney function, is a required part of the treatment plan for secondary deficiency.