Medium-chain Acyl-CoA Dehydrogenase Deficiency Identified by MS/MS Newborn Screening Challenges

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is an inborn error of metabolism resulting in the absence or reduced activity of the enzyme responsible for the β-oxidation of medium-chain fatty acids. MCAD deficiency can lead to metabolic decompensation, presenting as hypoketotic hypoglycaemia, hepatic encephalopathy (Reye-like syndrome), or death regardless of the patient's age.

Blood samples in the national newborn screening programme were collected using 903 filter paper (dry blood spot - DBS). Routine dried blood spots from newborn screening (NBS) were analysed by flow injection and derivatised tandem mass spectrometry method (MS/MS). Positive screening cases in the MCAD deficiency profile were verified through GC/MS urine organic acid profiling and enzymatic and/or molecular testing.

A total of 3,806,166 newborns were screened between 2014-2024, resulting in the identification of 94 cases of MCAD deficiency. Analysis of the obtained results revealed a consistent pattern in the levels of octanoylcarnitine (C8), hexanoylcarnitine (C6), and decanoylcarnitine (C10) acylcarnitines, as well as the C8/C10 ratio across these cases. Only one case of confirmed MCAD deficiency with an atypical acylcarnitine profile was found.

The use of tandem mass spectrometry has enabled the inclusion of MCAD deficiency in newborn screening programmes. This has facilitated early detection, diagnosis, and initiation of therapeutic interventions to prevent metabolic decompensation. We emphasize the need for repeated sampling and further testing if C8 is even slightly elevated.