Evaluation of newborn screening for medium chain acyl-CoA dehydrogenase deficiency in 275 000 babies

Abstract

Objective - To evaluate newborn screening by tandem mass spectrometry for detection of medium chain acyl-CoA dehydrogenase (MCAD) deficiency, a fatty acid oxidation disorder with significant mortality in undiagnosed patients. Design - The following were studied: (a) 13 clinically detected MCAD deficient subjects, most homozygous for the common A985G mutation, whose newborn screening sample was available; (b) 275 653 consecutive neonates undergoing routine newborn screening. Screened infants with blood octanoylcarnitine levels ≥ 1 μmol/l were analysed for the A985G mutation, had analysis of plasma and repeat blood spot acylcarnitines and urinary organic acids, and had fibroblast fatty acid oxidation or acylcarnitine studies. Result - Twelve of the 13 patients later diagnosed clinically had newborn octanoylcarnitine levels > 2.3 μmol/l. Twenty three screened babies had initial octanoylcarnitine levels ≥ 1 μmol/l. Eleven of 12 babies with persistent abnormalities had metabolite and/or enzyme studies indicating MCAD deficiency. Only four were homozygous for the A985G mutation, the remainder carrying one copy. Conclusions - Most patients with symptomatic MCAD deficiency could be detected by newborn screening. Infants actually detected had a lower frequency of A985G alleles than clinically diagnosed cases and may have a lower risk of becoming symptomatic.