Newborn Screening for MCAD Deficiency: Experience of the First Three Years in British Columbia, Canada

Background: Medium Chain Acyl-CoA Dehydrogenase (MCAD) Deficiency is an autosomal recessive disorder of fatty acid oxidation, with potential fatal outcome. MCAD deficiency is diagnosed by acylcarnitine analysis on newborn screening blood spot cards by tandem mass spectrometry. Early diagnosis of MCAD and presymptomatic treatment can potentially reduce morbidity and mortality. Objectives: To evaluate incidence, clinical outcome, biochemical and molecular phenotype of MCAD cases detected in the first three years of newborn screening in British Columbia (BC). Methods and Results: Medium chain length acylcarnitines, octanoylcarnitine (C8) and decanoylcarnitine (C10), were measured on newborn screening blood spot cards. Out of 121,000 live births, 17 newborns had C8 values above the screening cut-off of 0.38 umol/L. Ten newborns had elevated C8 on repeat cards and were investigated further. Both C8 and C8/C10 ratios remained abnormal in all confirmed MCAD cases. Positive predictive value of screening was 58% with no false negative results. Seven patients were homozygous for the common c.985A>G MCAD mutation and three others were compound heterozygous for the c.985A>G and a second mutation. Two novel mutations were identified (c.260T>C and c.382T>A). The estimated incidence of MCAD was ~1:12,000 live births. Upon frequent feeding and carnitine supplementation, none of the patients had metabolic crises or adverse outcomes. Conclusion: Frequency of MCAD in BC is comparable to reports from other newborn screening programs. Persistence of elevated C8 levels and C8/C10 ratios in confirmed MCAD cases suggest that these are sensitive markers for newborn screening. Early detection and treatment have successfully prevented adverse health outcomes in patients with MCAD. Contexte : Le déficit en acyl-coenzyme A déshydrogénase (DACAD) des acides gras à chaîne moyenne est un trouble autosomique récessif d'oxydation des acides gras qui peut être mortel. Ce déficit est diagnostiqué par spectrométrie de masse en tandem des acylcarnitines dans le sang du nouveau-né (une tache de sang est recueillie sur une fiche en papier). Il est possible que le diagnostic précoce et le traitement avant l'apparition des symptômes réduisent la morbidité et la mortalité liées au DACAD. Objectifs : Évaluer l'incidence, les résultats cliniques et les phénotypes biochimiques et moléculaires des cas de DACAD décelés au cours des trois premières années du programme de dépistage des nouveau-nés en Colo