Primary carnitine deficiency

Mutations in the SLC22A5 gene cause primary carnitine deficiency. This gene provides instructions for making a protein called OCTN2 that transports carnitine into cells. Cells need carnitine to bring certain types of fats (fatty acids) into mitochondria, which are the energy-producing centers within cells. Fatty acids are a major source of energy for the heart and muscles. During periods of fasting, fatty acids are also an important energy source for the liver and other tissues.

Mutations in the SLC22A5 gene result in an absent or dysfunctional OCTN2 protein. As a result, there is a shortage (deficiency) of carnitine within cells. This deficiency, as well as potential build-up of fatty acids within the cells, causes the signs and symptoms of the condition.

Primary carnitine deficiency can have a wide range of presentations and the age at diagnosis varies. Affected individuals may be diagnosed due to metabolic decompensation in infancy (between ages 3 months to 2 years); cardiomyopathy in childhood (between 2 and 4 years of age on average); or fatigability in adulthood. Some affected individuals lack symptoms entirely.

Although the condition is typically associated with the infantile presentation in about half of affected individuals and the childhood myopathic presentation in the other half, affected adults with mild or no symptoms have been reported. Several women have been diagnosed after newborn screening identified low carnitine levels in their infants. About half of those women complained of fatigability, whereas the other half were asymptomatic. In some cases, affected women can have decreased stamina or worsening of cardiac arrhythmia during pregnancy, suggesting that the condition may manifest or exacerbate during pregnancy.

Primary carnitine deficiency is inherited in an autosomal recessive manner. Individuals have two copies of each gene, one of which is inherited from each parent. For an individual to have an autosomal recessive condition, he/she must have a mutation in both copies of the disease-causing gene. The parents of an affected individual, who each likely have one mutated copy, are referred to as carriers. Carriers typically do not have any signs or symptoms of the condition. When two carriers for an autosomal recessive condition have children together, each child has a 25% (1 in 4) risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25% risk to not have the condition and not be a carrier.

Infantile metabolic and childhood myopathic presentations of the condition can be fatal if untreated. However, long-term prognosis is excellent with oral carnitine supplementation. If the disorder goes unrecognized, death can occur due to cardiac failure, arrhythmias or sudden death. Hypoglycemia or sudden deaths from arrhythmias (even without cardiomyopathy) have been reported in affected individuals who stop their carnitine supplementation against medical advice.

Individuals who have questions about their specific prognosis should speak with their health care provider.

Most individuals with primary carnitine deficiency are followed by a metabolic doctor as well as a dietician familiar with this condition. Certain treatments may be advised for some children but not others. Treatment is often needed throughout life. The main treatment for this condition is lifelong use of L- carnitine, which is a natural substance that helps body cells make energy. It also helps the body get rid of harmful wastes. L-carnitine can reverse the heart problems and muscle weakness caused by this condition.

In addition to L-carnitine, infants and young children with primary carnitine deficiency need to eat frequently to prevent a metabolic crisis. In general, it is often suggested that infants be fed every four to six hours. But some babies need to eat even more frequently than this. Many teens and adults with this condition can go without food for up to 12 hours without problems. Some children and teens benefit from a low-fat, high carbohydrate diet. Any diet changes should be made under the guidance of a metabolic specialist and/or dietician familiar with this condition. Ask your doctor whether your child needs to have any changes in his or her diet. Other treatments usually need to be continued throughout life.

Infants and children with this condition need to eat extra starchy food and drink more fluids during any illness, even if they may not feel hungry, because they could have a metabolic crisis. Children who are sick often do not want to eat. If they won’t or can’t eat, they may need to be treated in the hospital to prevent serious health problems.

The Newborn Screening Coding and Terminology Guide has information on the standard codes used for newborn screening tests. Using these standards helps compare data across different laboratories. This resource was created by the National Library of Medicine.