Carnitine is a substance that helps the body convert fats into energy by acting as a shuttle, moving fatty acids into the mitochondria. This process is how the body generates fuel, especially during periods without food. Carnitine Uptake Deficiency (CUD) is a metabolic disorder that disrupts this system. It prevents the body from properly bringing carnitine into cells, leading to an inability to use certain fats for energy and causing unused fatty acids to accumulate.
The Genetic Basis of Carnitine Uptake Deficiency
Carnitine Uptake Deficiency is an inherited condition following an autosomal recessive pattern. For a child to be affected, they must inherit a non-working copy of the responsible gene from each parent. The parents are considered carriers, each with one copy of the gene variant, and show no signs of the disorder. With each pregnancy, there is a one in four chance that the child will inherit both non-working copies and have CUD.
The gene responsible for CUD is SLC22A5, which holds the instructions for creating a protein called the organic cation/carnitine transporter 2, or OCTN2. The OCTN2 protein’s job is to transport carnitine from the blood into the body’s cells. When mutations occur in the SLC22A5 gene, the resulting OCTN2 protein is either non-functional or works poorly. This defect in the transport system leads to a lack of carnitine within cells and causes the body to lose carnitine through urine.
Signs and Symptoms
The signs of Carnitine Uptake Deficiency vary and often appear between infancy and early childhood, from three months to seven years of age. Symptoms are frequently triggered by periods of fasting or common illnesses, such as a stomach virus, that reduce food intake. An otherwise healthy-appearing infant may suddenly become very tired, difficult to wake, irritable, and have a poor appetite.
There are two primary ways CUD presents itself. The first is a metabolic crisis, involving dangerously low blood sugar (hypoglycemia) without the presence of ketones. This can also lead to elevated ammonia levels in the blood, vomiting, and behavioral changes.
The second presentation involves the heart, where a lack of energy can lead to cardiomyopathy, a condition where the heart becomes enlarged and weakened. In older children and adults, symptoms might be more subtle and develop gradually, including progressive muscle weakness and fatigue. Without treatment, these complications can lead to heart failure, coma, or sudden death.
Diagnosis and Screening
Most CUD cases are identified shortly after birth through routine newborn screening. This process involves a heel prick to collect a blood sample on filter paper. The dried blood spot is analyzed using tandem mass spectrometry to measure the concentration of free carnitine (C0). An abnormally low level of free carnitine flags the infant for further investigation.
If the initial screen is positive, confirmatory testing is required. These tests include a plasma carnitine analysis to measure the levels of free and total carnitine, which will be extremely low in individuals with CUD. A urine test will show high levels of excreted carnitine. Genetic testing can also identify mutations in the SLC22A5 gene.
It is also important to test the infant’s mother, as a low carnitine level in a newborn can reflect the mother having an undiagnosed case of CUD herself. Distinguishing between the two is a direct part of the diagnostic process.
Treatment and Management
The treatment for Carnitine Uptake Deficiency is lifelong supplementation with L-carnitine. Administered orally in large doses, it increases carnitine in the body’s fluids and inside the cells. Restoring carnitine levels allows the body to properly use fatty acids for energy and can reverse heart problems and muscle weakness. During a metabolic crisis, L-carnitine can be administered intravenously in a hospital.
A main part of managing CUD is avoiding prolonged fasting, which can trigger a metabolic event. Infants and young children must eat frequently, often every four to six hours, and may need to be woken up for night feedings to prevent their blood sugar from dropping. During illness, consuming extra fluids and starchy foods is necessary even if they do not feel hungry.
Long-term management includes regular monitoring by a medical team. This involves follow-up appointments with a metabolic specialist to monitor plasma carnitine levels and adjust treatment as needed. Individuals with heart-related complications will also require ongoing care from a cardiologist to manage their cardiac health.
Living with Carnitine Uptake Deficiency
With early detection and consistent, lifelong treatment, the prognosis for individuals with CUD is positive. People who adhere to L-carnitine supplementation and dietary management can lead full, healthy lives with a normal life expectancy. Newborn screening has greatly improved this outlook, allowing treatment to begin before severe symptoms or damage can occur.
It is recommended that individuals with CUD carry emergency information or wear a medical alert bracelet. Educating family members, friends, and school personnel about the condition is also helpful. While the treatment is for life, it enables the body to function properly.