Clinical Information

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.(1) 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 can be measured by tandem mass spectrometry. 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 or 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/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.

The following disorders are detectable by acylcarnitine analysis. However, further confirmatory testing is required for most of these conditions because an acylcarnitine profile can be suggestive of more than one condition.

Fatty Acid Oxidation Disorders:

-Carnitine palmitoyltransferase I deficiency

-Medium-chain 3-ketoacyl-CoA thiolase deficiency

-Dienoyl-CoA reductase deficiency

-Short-chain acyl-CoA dehydrogenase deficiency

-Medium/Short-chain 3-hydroxyacyl-CoA dehydrogenase deficiency

-Medium-chain acyl-CoA dehydrogenase) deficiency

-Long-chain 3-hydroxyacyl-CoA dehydrogenase) deficiency and trifunctional protein deficiency

-Very long-chain acyl-CoA dehydrogenase deficiency

-Carnitine palmitoyl transferase type II deficiency

-Carnitine-acylcarnitine translocase deficiency

-Electron transfer flavoprotein (ETF) deficiency, ETF-dehydrogenase deficiency (multiple acyl-CoA dehydrogenase deficiency; glutaric acidemia type II)

Organic Acid Disorders:

-Glutaryl-CoA dehydrogenase deficiency (glutaric acidemia type I)

-Propionic acidemia

-Methylmalonic acidemia

-Isovaleric acidemia

-3-Hydroxy-3-methylglutaryl-CoA carboxylase deficiency

-3-Methylcrotonyl carboxylase deficiency

-Biotinidase deficiency

-Multiple carboxylase deficiency

-Isobutyryl-CoA dehydrogenase deficiency

-2-Methylbutyryl-CoA dehydrogenase deficiency

-Beta-ketothiolase deficiency

-Malonic aciduria

-Ethylmalonic encephalopathy

Glutamate formiminotransferase deficiency (formiminoglutamic aciduria)