Primary carnitine deficiency

Other Names: Systemic primary carnitine deficiency; Carnitine uptake defect; Carnitine deficiency, systemic, due to defect in renal reabsorption of carnitine; Carnitine plasma-membrane transporter deficiency; Carnitine transporter deficiency; Carnitine uptake deficiency

Primary carnitine deficiency is a genetic condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). Problems related to primary carnitine deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.

Cause

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. Without carnitine, fatty acids cannot enter mitochondria and be used to make energy. Reduced energy production can lead to some of the features of primary carnitine deficiency, such as muscle weakness and hypoglycemia. Fatty acids may also build up in cells and damage the liver, heart, and muscles. This abnormal buildup causes the other signs and symptoms of the disorder.

Inheritance

Autosomal recessive inheritance, a 25% chance

Primary carnitine deficiency is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. Most often, the parents of an individual with an autosomal recessive disorder are carriers, which means they each carry one copy of the mutated gene. Carriers of SLC22A5 gene mutations may have some signs and symptoms related to the condition.

Signs and symptoms

Signs and symptoms of primary carnitine deficiency typically appear during infancy or early childhood and can include severe brain dysfunction (encephalopathy), a weakened and enlarged heart (cardiomyopathy), confusion, vomiting, muscle weakness, and low blood sugar (hypoglycemia). The severity of this condition varies among affected individuals. Some people with primary carnitine deficiency are asymptomatic, which means they do not have any signs or symptoms of the condition. All individuals with this disorder are at risk for heart failure, liver problems, coma, and sudden death. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Acute encephalopathy
• Bilateral tonic-clonic seizure with focal onset
• Clumsiness
• Confusion(Disorientation)
• Elevated hepatic transaminase(High liver enzymes)
• Hepatomegaly(Enlarged liver)
• Neck muscle weakness(Floppy neck)
• Vomiting(Throwing up)

Diagnosis

The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level. When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts. 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.

Treatment

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 medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition.

• Levocarnitine (Brand name: Carnitor®) Treatment of primary and secondary carnitine deficiency.

Prognosis

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.

Incidence

The incidence of primary carnitine deficiency in the general population is approximately 1 in 100,000 newborns. In Japan, this disorder affects 1 in every 40,000 newborns.

NIH genetic and rare disease info

• NIH info on Primary carnitine deficiency

Primary carnitine deficiency is a rare disease.

Primary carnitine deficiency Resources
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