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: 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 diagnosis for pregnancies at increased risk are possible if the SLC22A5 pathogenic variants in the family are known.
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