Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCADD) Newborn Screening in Italy: Five Years’ Experience from a Nationwide Program

Abstract

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is an autosomal recessive disorder of fatty acid oxidation that can have life-threatening consequences if not promptly treated. Early diagnosis by means of newborn screening (NBS) has the potential to reduce morbidity and mortality. This study investigates the incidence and molecular characteristics of MCADD in Italy over a five-year period within the framework of the expanded NBS program. Between January 2019 and December 2023, a total of 1,976,473 newborns were screened. Ninety unrelated neonates were diagnosed with MCADD, providing an estimated incidence of 1/21,960 live births (95% CI: 1:17,780–1:27,200), comparable to rates reported in other Mediterranean populations. Molecular analysis identified c.985A>G (p.Lys329Glu) as the most frequent pathogenic ACADM gene variant, observed in 56 patients (63%), including eighteen patients (20%) who were homozygous and thirty-eight (43%) who were compound heterozygotes for this variant. To our knowledge, this study represents the first comprehensive investigation to document the high prevalence of MCADD among the Italian population.