title: Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: a global perspective.
abstract: As judged by tandem mass spectrometry blood spot screening, the incidence of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is 1:14 600 (CI 95%: 1:13 500-1:15 900) in almost 8.2 million newborns worldwide and is 2- to-3 fold higher than that identified in the same populations after clinical presentation. In mass-screened newborn populations, the 985A>G (K329E) mutation accounts for 54-90% of disease alleles, with homozygotes representing about 47-80% of MCAD deficiency cases. Worldwide, octanoylcarnitine levels are an effective primary screen for MCAD deficiency in newborns. Newborns homozygous for the 985A < G mutation have higher octanoylcarnitine levels than do those compound heterozygous for 985A < G and those with other genotypes. Time of sampling after birth also significantly affects octanoylcarnitine levels in MCAD-deficient newborns. Tandem mass spectrometry newborn blood spot screening for MCAD deficiency is accurate and effective, reduces morbidity and mortality, and merits expansion to other populations worldwide.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA. wrhead@mcw.edu
authors.forename: William J
authors.initials: WJ
authors.lastname: Rhead
mesh_terms: D042964:Acyl-CoA Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D005820:Genetic Testing; D005838:Genotype; D014943:Global Health; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D008052:Lipid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis* / Q000201:enzymology / Q000453:epidemiology; D009154:Mutation; D015997:Neonatal Screening; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D011795:Surveys and Questionnaires; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D042964:Acyl-CoA Dehydrogenase; C008698:octanoylcarnitine; D002331:Carnitine