Acylcarnitines, Quantitative, Plasma
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Acylcarnitine analysis enables the diagnosis of many disorders of fatty acid oxidation and several organic acidurias, as relevant enzyme deficiencies cause the accumulation of specific acyl-CoAs. Fatty acid oxidation (FAO) plays a major role in energy production during periods of fasting. When the body's supply of glucose is depleted, fatty acids are mobilized from adipose tissue, taken up by the liver and muscles, and oxidized to acetyl-CoA. In the liver, acetyl-CoA is the building block for the synthesis of ketone bodies, which enter the blood stream and provide an alternative substrate for production of energy in other tissues when the supply of glucose is insufficient to maintain a normal level of energy. The acyl groups are conjugated with carnitine to form acylcarnitines, which are measured by tandem mass spectrometry (MS/MS). Diagnostic results are usually characterized by a pattern of significantly elevated acylcarnitine species compared to normal and disease controls.
In general, more than 20 inborn errors of metabolism can be identified using this method including FAO disorders and organic acidurias. The major clinical manifestations associated with individual FAO disorders include hypoketotic hypoglycemia, variable degrees of liver disease and failure, skeletal myopathy, dilated/hypertrophic cardiomyopathy, and sudden or unexpected death. Organic acidurias also present as acute life-threatening events early in life with metabolic acidosis, increased anion gap, and neurologic distress. Patients with any of these disorders are at risk of developing fatal metabolic decompensations following the acquisition of even common infections. Once diagnosed, these disorders can be treated by avoidance of fasting, special diets, and cofactor and vitamin supplementation.
Analysis of acylcarnitines in blood and bile spots represents the first level of evaluation of a complete postmortem investigation of a sudden or unexpected death of an individual. Additional confirmatory testing is recommended. The diagnosis of an underlying FAO disorder or organic aciduria allows genetic counseling of the family, including the possible option of future prenatal diagnosis, and testing of at-risk family members of any age.
Disorders Detectable by Acylcarnitine Analysis*
Fatty Acid Oxidation Disorders:
-Carnitine palmitoyltransferase I (CPTI) deficiency
-Medium-chain 3-ketoacyl-CoA thiolase (MCKAT) deficiency
-Dienoyl-CoA reductase deficiency
-Short-chain acyl-CoA dehydrogenase (SCAD) deficiency
-Medium/Short-chain 3-hydroxyacyl-CoA dehydrogenase (M/SCHAD) deficiency
-Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency
-Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency & trifunctional protein deficiency
-Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency
-Carnitine palmitoyl transferase type II (CPT-II) deficiency
-Carnitine-acylcarnitine translocase (CACT) deficiency
-Electron transfer flavoprotein (ETF) deficiency, ETF-dehydrogenase deficiency (multiple acyl-CoA dehydrogenase deficiency [MADD]; glutaric acidemia type II)
Organic Acid Disorders:
-Glutaryl-CoA dehydrogenase deficiency (glutaric acidemia type I)
-3-hydroxy-3-methylglutaryl-CoA carboxylase deficiency
-3-Methylcrotonyl carboxylase deficiency
-Multiple carboxylase deficiency
-Isobutyryl-CoA dehydrogenase deficiency
-2-Methylbutyryl-CoA dehydrogenase deficiency
-Glutamate formiminotransferase deficiency (Formiminoglutamic aciduria)
*Further confirmatory testing is required for most of these conditions because an acylcarnitine profile can be suggestive of more than 1 condition.
Diagnosis of fatty acid oxidation disorders and several organic acidurias in plasma specimens
Evaluating treatment during follow-up of patients with fatty acid beta-oxidation disorders and several organic acidurias
An interpretive report is provided. The individual quantitative results support the interpretation of the acylcarnitine profile but are not diagnostic by themselves. The interpretation is based on pattern recognition.
Abnormal results are not sufficient to conclusively establish a diagnosis of a particular disease. To verify a preliminary diagnosis based on an acylcarnitine analysis, independent biochemical (eg, in vitro enzyme assay) or molecular genetic analyses are required.
For information on the follow-up of specific acylcarnitine elevations, see Special Instructions for the following algorithms:
-Newborn Screening Follow-up for Elevations of C8, C6, and C10 Acylcarnitines (also applies to any plasma or serum C8, C6, and C10 acylcarnitine elevations)
-Newborn Screening Follow-up for Isolated C4 Acylcarnitine Elevations (also applies to any plasma or serum C4 acylcarnitine elevation)
-Newborn Screening Follow-up for Isolated C5 Acylcarnitine Elevations (also applies to any plasma or serum C5 acylcarnitine elevation)
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
In a few instances, false-negative results occur in the analysis of acylcarnitine profiles. For some disorders, such as medium-chain acyl-CoA dehydrogenase (MCAD) deficiency, the calculation of ratios between different acylcarnitine species provides a discriminate factor to overcome such problems. Where applicable, the calculation of such ratios will be incorporated in the routine acylcarnitine analysis. Informative profiles may also not be detected in some disorders where the accumulation of diagnostic acylcarnitines is a reflection of the residual activity of the defective enzyme, the dietary load of precursors, and the anabolic/catabolic and treatment status of a patient.
Patients with carnitine deficiency may not exhibit abnormally high acylcarnitine concentrations. If the results are indicative for carnitine deficiency, the interpretation will include a remark that this limits the diagnostic value of the test and repeat analysis may be considered following carnitine supplementation.
Follow-up testing such as in vitro enzyme assays or molecular genetic testing may be recommended following abnormal acylcarnitine results. It is not advisable to intentionally stress the patient's metabolism (eg, fasting test) prior to specimen collection for acylcarnitine analysis.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Matern D: Acylcarnitines, including in vitro loading tests. In Laboratory Guide to the Methods in Biochemical Genetics. Edited by N Blau, M Duran, KM Gibson. Springer Verlag 2008 pp 171-206
2. Rinaldo P, Cowan TM, Matern D: Acylcarnitine profile analysis. Genet Med 2008;10:151-156
3. Smith EH, Matern D: Acylcarnitine analysis by tandem mass spectrometry. Curr Protoc Hum Genet 2010;Chapter 17:Unit 17.8.1-20