Interpretive Handbook

Carnitine and its esters are required for normal energy metabolism and serve 4 primary functions:

-Importing long-chain fatty acids into the mitochondria

-Exporting naturally occurring short-chain acyl-CoA groups from the mitochondria

-Buffering the ratio of free CoA to esterified CoA

-Removing potentially toxic acyl-CoA groups from the cells and tissues

Evaluation of carnitine in serum, plasma, tissue, and urine screens patients for suspected primary disorders of the carnitine cycle, or secondary disturbances in carnitine levels as a result of organic acidemias and fatty acid oxidation disorders. In the latter, acyl-CoA groups accumulate and are excreted into the urine and bile as carnitine derivatives, resulting in a secondary carnitine deficiency. More than 100 such primary and secondary disorders have been described. Individually, the incidence of these disorders varies from <1:10,000 to >1:1,000,000 live births. Collectively, their incidence is approximately 1:1,000 live births. Primary carnitine deficiency has an incidence of approximately 1 in 21,000 live births based on Minnesota newborn screening data.

Other conditions which could cause an abnormal carnitine level include neuromuscular diseases, gastrointestinal disorders, familial cardiomyopathy, renal tubulopathies and chronic renal failure (dialysis), and prolonged treatment with steroids, antibiotics (pivalic acid), anticonvulsants (valproic acid), and total parenteral nutrition.

Follow up testing is required to differentiate primary and secondary carnitine deficiencies and to elucidate the exact cause.

Evaluation of patients with a clinical suspicion of a wide range of conditions including organic acidemias and fatty acid oxidation disorders

Monitoring carnitine treatment

When abnormal results are detected, a detailed interpretation is given, including an overview of the results and of their significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional biochemical testing and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.

Increased values may be obtained after carnitine supplementation or meat consumption.

FREE

77-214 nmol/mg of creatinine

TOTAL

180-412 nmol/mg of creatinine

RATIO

Acyl to free: 0.7-3.4

1. Chalmers RA, Roe CR, Stacey TE, et al: Urinary excretion of l-carnitine and acylcarnitines by patients with disorders of organic acid metabolism: evidence for secondary insufficiency of l-carnitine. Ped Res 1984;18:1325-1328

2. Scaglia F, Wang YH, Singh RH, et al: Defective urinary carnitine transport in heterozygotes for primary carnitine deficiency. Genet Med 1998;1:34-39

3. Scaglia F, Longo N: Primary and secondary alterations of neonatal carnitine metabolism. Semin Perinatol 1999;23:152-161

4. Longo N, Amat di San Filippo C, Pasquali M: Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet 2006;142C(2):77-85

5. Zammit VA, Ramsay RR, Bonomini M, Arduini A: Carnitine, mitochondrial function and therapy. Adv Drug Deliv Rev 2009;61(14):1353-62