Systemic primary carnitine deficiency

Systemic primary carnitine deficiency

Description, Causes and Risk Factors:

Abbreviation: SPCD.

Systemic primary carnitine deficiency, (SPCD) also known as carnitine uptake defect, carnitine transporter deficiency or systemic carnitine deficiency is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The specific transporter involved with SPCD is OCTN2, coded for by the SLC22A5 gene located on chromosome 5. SPCD is inherited in an autosomal recessive manner, with mutated alleles coming from both parents.

Acute episodes due to SPCD are often preceded by metabolic stress such as extended fasting, infections or vomiting. Cardiomyopathy can develop in the absence of an acute episode, and can result in death. SPCD leads to increased carnitine excretion in the urine and low levels in plasma. In most locations with expanded newborn screening, SPCD can be identified and treated shortly after birth. Treatment with high doses of carnitine supplementation is effective, but needs to be rigouously maintained for life.

SPCD is an autosomal recessive condition, meaning a mutated allele must be inherited from each parent for an individual to be affected. The gene responsible for the OCTN2 carnitine transporter is SLC22A5, located at 5q31.1-32. SLC22A5 is regulated by peroxisome proliferator-activated receptor alpha. The transporter, OCTN2, is located in the apical membrane of the renal tubular cells, where it plays a role in tubular reabsorption.

The defective OCTN2 is unable to recapture carnitine prior to its excretion in urine, leading to the characteristic biochemical findings of massively increased urine carnitine levels and significantly decreased plasma carnitine levels. Decreased levels of plasma carnitine inhibit fatty acid oxidation during times of excessive energy demand. Carnitine is needed to transport long chain fatty acids into the mitochondria, where they can be broken down to produce acetyl-CoA. Individuals with SPCD cannot produce ketone bodies as energy due to the interruption of fatty acid oxidation. Although SPCD is an autosomal recessive condition, heterozygotes have been shown to be at an increased risk for developing benign cardiomyopathy compared to wild type individuals.

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.

In Taiwan, the incidence of SPCD in newborns was estimated to be approximately 1:67,000, while maternal cases were identified at a higher frequency of approximately 1:33,000. The increased incidence of SPCD in mothers compares to newborns is not completely understood. Estimates of SPCD in Japan have showed a similar incidence of 1:40,000.


The presentation of patient with SPCD can be incredibly varied, from asymptomatic to lethal cardiac manifestations.Early cases were reported with liver dysfunction, muscular findings (weakness and underdevelopment), hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in urine.Patients who present clinically with SPCD fall into two categories, a metabolic presentation with hypoglycemia and a cardiac presentation characterized by cardiomyopathy. Muscle weakness can be found with either presentation.


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.

Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment. Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life.Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy.Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well. The long-term outcomes for asymptomatic adults with SPCD is not known, but the discovery of mothers with undiagnosed cardiomyopathy and SPCD has raised the possibility that identification and treatment may prevent adult onset manifestations.


Metabolic decompensation and skeletal and cardiac muscle functions improve with 100-400 mg/kg/day oral levocarnitine (L-carnitine) if it is started before irreversible organ damage occurs. Hypoglycemic episodes are treated with intravenous dextrose infusion; cardiomyopathy requires management by specialists in cardiology. Prevention of primary manifestations: The manifestations of CDSP can be prevented by use of oral L-carnitine supplementation to maintain normal plasma carnitine concentrations. Surveillance: Suggested: (1) echocardiogram and electrocardiogram: annually during childhood and less frequently in adulthood; (2) plasma carnitine concentration: monitor frequently until levels reach the normal range, then, measure three times a year during infancy and early childhood, twice a year in older children, and annually in adults; (3) serum creatine kinase concentration and liver transaminases: consider measuring during acute illnesses. Agents/circumstances to avoid: Fasting longer than age-appropriate periods. Evaluation of relatives at risk: Measure plasma carnitine levels in sibs of an affected individual. Pregnancy management: Pregnant women with CDSP require close monitoring of plasma carnitine levels and increased carnitine supplementation as needed to maintain normal plasma carnitine levels.

NOTE: The above information is for processing purpose. The information provided herein should not be used during any medical emergency or for the diagnosis or treatment of any medical condition.

DISCLAIMER: This information should not substitute for seeking responsible, professional medical care.


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