Pitfalls in the diagnosis of carnitine palmitoyltransferase 1 deficiency.

Objectives: Carnitine palmitoyltransferase 1 A (CPT1A) deficiency is an ultra-rare autosomal recessive disorder of the carnitine cycle caused by biallelic pathogenic variants in the CPT1A gene. It mainly presents with a hepatic phenotype and is a target disease of newborn screening programs worldwide. Disease-specific and diagnostic abnormalities of CPT1A deficiency comprise elevated concentrations of free carnitine as well as an elevated metabolite ratio [C0/(C16 + C18)] in blood, but the ideal sample material has been a matter of debate.

Methods: We present biochemical data of five CPT1A deficient patients, of whom four were diagnosed by newborn screening from dried blood spots.

Results: Our cases demonstrate that acylcarnitine profiles and especially concentrations of free carnitine can be normal in plasma in infants with CPT1AD at confirmation diagnosis after screening and during follow-up. Even the [C0/(C16 + C18)] ratio yielded normal results in some cases.

Conclusions: Our data show, that dried blood is the preferred sample material for the diagnosis of CPT1A deficiency as it is superior to serum/plasma with respect to diagnostic sensitivity and reliability in quantification of the ratio [C0/(C16 + C18)]. CPT1A deficiency can be missed, if the analysis is only performed in serum or plasma, and confirmatory diagnostics in serum or plasma after screening can be false negative.