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Inborn errors of metabolism are a heterogeneous group of conditions which frequently cause diagnostic difficulties due to their wide range of presenting features. Because many of these disorders overlap considerably in their presentation, a clinical suspicion of metabolic disease often leads to the taking of a “first line metabolic screen”, which will typically include all or a combination of the following:
▶. blood for ammonia and lactate measurement
▶. urine for organic acid analysis ± glycosaminoglycans
▶. blood for amino acids
▶. blood for acylcarnitine analysis.
This article is intended to aid the non-metabolic specialist in understanding the method and rationale for measuring acylcarnitines when investigating children with suspected inborn errors of metabolism and help one appreciate what it does, and more importantly does not, tell about a patient. It is not intended to be a substitute for close communication with one's local metabolic laboratory!
Carnitine is a small intracellular molecule, which facilitates the transport of larger molecules, especially fatty acids, across cellular compartments. Fatty acid molecules (esterified to coenzyme A) esterify onto the carnitine molecule, as shown in fig 1, to form an acylcarnitine species.
The resulting acylcarnitine molecule can then be transported across membranes using enzyme systems that recognise the carnitine moiety to facilitate transfer, such as the carnitine palmitoyl transferase shuttle illustrated below. The carnitine moiety is then again swapped for coenzyme A within the mitochondrion and the carnitine recycled back to the cytosol (fig 2).
The ability of carnitine to esterify to larger organic molecules underlies the basis of its use in diagnosing inborn errors of metabolism. For example, an enzyme defect in the β-oxidation of fatty acids inside the mitochondrion will lead to a rise in fatty acyl-coenzyme A molecules of …
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Provenance and peer review Commissioned; externally peer reviewed.
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