Systemic Primary Carnitine Deficiency

In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993.
[updated ].


Clinical characteristics: Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. It encompasses a broad clinical spectrum including the following:

  1. Metabolic decompensation in infancy typically presenting between age three months and two years with episodes of hypoketotic hypoglycemia, poor feeding, irritability, lethargy, hepatomegaly, elevated liver transaminases, and hyperammonemia triggered by fasting or common illnesses such as upper respiratory tract infection or gastroenteritis

  2. Childhood myopathy involving heart and skeletal muscle with onset between age two and four years

  3. Pregnancy-related decreased stamina or exacerbation of cardiac arrhythmia

  4. Fatigability in adulthood

  5. Absence of symptoms

The latter two categories often include mothers diagnosed with CDSP after newborn screening has identified low carnitine levels in their infants.

Diagnosis/testing: Plasma carnitine levels are extremely reduced in CDSP. The diagnosis is established by identification of biallelic pathogenic variants in SLC22A5 or demonstration of reduced fibroblast carnitine transport.

Management: Treatment of manifestations: Metabolic decompensation and skeletal and cardiac muscle function 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: Maintain appropriate plasma carnitine concentrations with oral L-carnitine supplementation; prevent hypoglycemia with frequent feeding and avoiding fasting. Hospitalization for intravenous glucose administration for individuals who are required to fast for a procedure or who cannot tolerate oral intake due to illness such as gastroenteritis.

Prevention of secondary complications: Oral metronidazole and/or decreasing the carnitine dose usually results in the resolution of the fishy odor due to L-carnitine supplementation.

Surveillance: Echocardiogram and electrocardiogram: annually during childhood and less frequently in adulthood; monitor plasma carnitine concentration 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; evaluate serum creatine kinase concentration and liver transaminases 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.

Genetic counseling: CDSP is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for a pregnancy at increased risk are possible if the SLC22A5 pathogenic variants in the family are known.

Publication types

  • Review