title: Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: the importance of enzyme analysis to ascertain true MCAD deficiency.
abstract: The outcome was determined of population-wide neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency using tandem mass spectrometry (MS/MS) in The Netherlands, between October 2003 and September 2005. Prospective population-wide neonatal screening for MCAD deficiency was performed in the northern part of The Netherlands. In newborns with blood octanoylcarnitine (C(8:0)) concentrations > or =0.3 micromol/L, clinical and laboratory follow-up was initiated, including MCAD enzymatic measurements which played a decisive role. In a 2-year period, 66 216 newborns were investigated for MCAD deficiency and follow-up was initiated in 28 newborns. True-positives (n = 14) were identified based upon MCAD enzyme activity <50%, measured with hexanoyl-CoA as substrate. The observed prevalence of MCAD deficiency was 1/6600 (95% CI: 1/4100-1/17 400). In addition to an elevated C(8:0) concentration, a C(8:0)/C(10:0) molar ratio >5.0 turned out to differentiate between false-positives and true-positives. Measurement of MCAD activity using phenylpropionyl-CoA as a substrate further discriminated between newborns with MCAD deficiency and so-called mild MCAD deficiency. To summarize, neonatal screening for MCAD deficiency in the northern part of The Netherlands resulted in the predicted number of affected newborns. Measurement of MCAD activity in leukocytes or lymphocytes using phenylpropionyl-CoA as a substrate can be regarded as the gold standard to diagnose MCAD deficiency upon initial positive screening test results.
authors.affiliation: Division of Metabolic Diseases, Beatrix Children's Hospital, University Medical Center Groningen, University of Groningen, PO Box 30 001, 9700 RB, Groningen, The Netherlands t.g.j.derks@bkk.umcg.nl
authors.forename: T G J
authors.initials: TG
authors.lastname: Derks
authors.forename: T S
authors.initials: TS
authors.lastname: Boer
authors.forename: A
authors.initials: A
authors.lastname: van Assen
authors.forename: T
authors.initials: T
authors.lastname: Bos
authors.forename: J
authors.initials: J
authors.lastname: Ruiter
authors.forename: H R
authors.initials: HR
authors.lastname: Waterham
authors.forename: K E
authors.initials: KE
authors.lastname: Niezen-Koning
authors.forename: R J A
authors.initials: RJ
authors.lastname: Wanders
authors.forename: J M M
authors.initials: JM
authors.lastname: Rondeel
authors.forename: J G
authors.initials: JG
authors.lastname: Loeber
authors.forename: L P
authors.initials: LP
authors.lastname: Ten Kate
authors.forename: G P A
authors.initials: GP
authors.lastname: Smit
authors.forename: D-J
authors.initials: DJ
authors.lastname: Reijngoud
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D042964:Acyl-CoA Dehydrogenase / Q000032:analysis / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005189:False Positive Reactions; D005500:Follow-Up Studies; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D007962:Leukocytes / Q000201:enzymology; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D008214:Lymphocytes / Q000201:enzymology; D025202:Molecular Diagnostic Techniques / Q000592:standards; D015997:Neonatal Screening; D009426:Netherlands; D010865:Pilot Projects; D015995:Prevalence
chemical_list: D000214:Acyl Coenzyme A; C078024:phenylpropionyl-coenzyme A; D042964:Acyl-CoA Dehydrogenase