Clinical Information

Postmortem screening involves acylcarnitine analysis in blood and bile specimens to evaluate cases of sudden or unexpected death. Acylcarnitine analysis can diagnose disorders of fatty acid oxidation and several organic acidurias, as relevant enzyme deficiencies cause the accumulation of specific acyl-CoAs measured by this assay.(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 are 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 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. Urine organic acids can also be analyzed from urine spotted on filter paper, see OAUS / Organic Acids Screen, Urine Spot. 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:

-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-Transferring Flavoproteins (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 

*Additional confirmatory testing is required for most of these conditions because an acylcarnitine profile can be suggestive of more than one condition.

For more information see Postmortem Screening Algorithm for Fatty Acid Oxidation Disorders and Organic Acidurias.