Journal of Inherited Metabolic Disease

, Volume 29, Issue 2–3, pp 370–377 | Cite as

Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: A global perspective

SSIEM SYMPOSIUM 2005

Summary

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.

Keywords

Carnitine Congenital Adrenal Hyperplasia Newborn Screening Neonatal Screening Electrospray Tandem Mass Spectrometry 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Andresen BS, Dobrowolski SF, O'Reilly L, et al (2001) Medium-chain acyl-CoA dehydrogenase (MCAD) mutations identified by MS/MS-based prospective screening of newborns differ from those observed in patients with clinical symptoms: identification and characterization of a new, prevalent mutation that results in mild MCAD deficiency. Am J Hum Genet 68: 1408–1418.PubMedCrossRefGoogle Scholar
  2. Annual Report, Indiana State Department of Health available at: http://www.state.in.us/isdh/programs/nbs/NBSStatistics.htm.Accessed 24 August 2005
  3. Bodamer O, Pollitt RJ (2005) Newborn screening and MCAD. Workshop results. 37th European Metabolic Group Meeting, Prague, Milupa, Friedrichsdorf.Google Scholar
  4. Chace DH, Kalas TA, Naylor EW (2002) The application of tandem mass spectrometry to neonatal screening for inherited disorders of intermediary metabolism. Annu Rev Genomics Hum Genet 3: 17–45.PubMedCrossRefGoogle Scholar
  5. Derks TG, Duran M, Waterham HR, Reijngoud DJ, Ten Kate LP, Smit GP (2005) The difference between observed and expected prevalence of MCAD deficiency in The Netherlands: a genetic epidemiological study. Eur J Hum Genet 13: 947–952.PubMedCrossRefGoogle Scholar
  6. Frazier DM. MS/MS newborn screening in NC 1997–2003: Outcomes and predicitive values of elevated results. APHL Newborn Screening and Genetics Testing Symposium available at: http://aphl.org/conferences/genetic_testing_symposium/MSMSStateandOrganizationreports/MSMS\20State-Frazier25.pdf.Accessed 17 August 2005.
  7. Gregersen N, Andresen BS, Corydon MJ, et al (2001) Mutation analysis in mitochondrial fatty acid oxidation defects: exemplified by acyl-CoA dehydrogenase deficiencies, with special focus on genotype—phenotype relationship. Hum Mutat 18: 169–189.PubMedCrossRefGoogle Scholar
  8. Hoffmann GF, von Kries R, Klose D, et al (2004) Frequencies of inherited organic acidurias and disorders of mitochondrial fatty acid transport and oxidation in Germany. Eur J Pediatr 163: 76–80.PubMedCrossRefGoogle Scholar
  9. Iafolla AK, Thompson RJ Jr, Roe CR (1994) Medium-chain acyl-coenzyme A dehydrogenase deficiency: clinical course in 120 affected children. J Pediatr 124: 409–415.PubMedCrossRefGoogle Scholar
  10. Kolvraa S, Gregersen N, Christensen E, Hobolth N (1982) In vitro fibroblast studies in a patient with C6–C10-dicarboxylic aciduria: evidence for a defect in general acyl-CoA dehydrogetnase. Clin Chim Acta 126: 53.PubMedCrossRefGoogle Scholar
  11. Liebl B, Nennstiel-Ratzel U, Roscher A, von Kries R (2003) Data required for the evaluation of newborn screening programmes. Eur J Pediatr 162: S57–61.PubMedCrossRefGoogle Scholar
  12. Lorey F (2004) California tandem MS research project. APHL Newborn Screening and Genetics Testing Symposium Available at: http://aphl.org/conferences/genetic_testing_symposium/MSMS StateandOrganizationreports/MSMS\20State-Lorey22.pdf.Accessed 17 August 2005.
  13. Maier EM, Liebl B, Roschinger W, et al (2005) Population spectrum of ACADM genotypes correlated to biochemical phenotypes in newborn screening for medium-chain acyl-CoA dehydrogenase deficiency. Hum Mutat 25: 443–452.PubMedCrossRefGoogle Scholar
  14. National Newborn Screening and Genetics Resource Center (2005) Current Newborn Screening (NBS) Conditions by State. Available at: http://genes-r-us.uthscsa.edu/.Accessed 28 July 2005.
  15. Nennstiel-Ratzel U, Arenz S, Maier EM, et al (2005) Reduced incidence of severe metabolic crisis or death in children with medium chain acyl-CoA dehydrogenase deficiency homozygous for c.985A>G identified by neonatal screening. Mol Genet Metab 85: 157–159.PubMedCrossRefGoogle Scholar
  16. Oerton J, Downing M, Andresen BS, et al (2005) Predictive value, clinical status and genotype of medium chain acyl CoA dehydrogenase deficiency (MCADD) ascertained by screening at one week of age using electrospray tandem mass spectrometry of underivatised blood spots: findings from a UK multicentre. J Inherit Metab Dis 28(Supplement 1): 9.Google Scholar
  17. Phillips P, Dalton RN, Besley G, et al (2005) Newborn screening for medium chain acyl CoA dehydrogenase deficiency (MCADD) at one week of age: octanoyl carnitine distributions from a multicentre study using electrospray tandem mass spectrometry of underivatised blood spot samples. J Inherit Metab Dis 28(Supplement 1): 9.Google Scholar
  18. Pourfarzam M, Morris A, Appleton M, Craft A, Bartlett K (2001) Neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency. Lancet 358: 1063–1064.PubMedCrossRefGoogle Scholar
  19. Shigematsu Y, Hirano S, Hata I, et al (2002) Newborn mass screening and selective screening using electrospray tandem mass spectrometry in Japan. J Chromatogr B Analyt Technol Biomed Life Sci 776: 39–48.PubMedGoogle Scholar
  20. Waddell L, Wiley V, Carpenter K, et al (2006) Medium-chain acyl-CoA dehydrogenase deficiency: genotype—biochemical phenotype correlations. Mol Genet Metab 87(1): 32.PubMedCrossRefGoogle Scholar
  21. Wilcken B, Carpenter K, Wiley V (2002) Neonatal screening for medium-chain acyl-CoA dehydrogenase deficiency. Lancet 359: 627–628.PubMedCrossRefGoogle Scholar
  22. Wilcken B, Wiley V, Hammond J, Carpenter K (2003) Screening newborns for inborn errors of metabolism by tandem mass spectrometry. N Engl J Med 348: 2304–2312.PubMedCrossRefGoogle Scholar
  23. Zytkovicz TH, Fitzgerald EF, Marsden D, et al (2001) Tandem mass spectrometric analysis for amino, organic, and fatty acid disorders in newborn dried blood spots: a two-year summary from the New England Newborn Screening Program. Clin Chem 47:1945–1955.PubMedGoogle Scholar

Copyright information

© SSIEM and Springer 2006

Authors and Affiliations

  1. 1.Departments of Pediatrics and PathologyMedical College of WisconsinMilwaukeeUSA

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