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Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: The importance of enzyme analysis to ascertain true MCAD deficiency

  • Original Article
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Journal of Inherited Metabolic Disease

Summary

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 (C8:0) concentrations ≥0.3 μmol/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 C8:0 concentration, a C8:0/C10:0 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.

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Authors and Affiliations

  1. 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 & G. P. A. Smit

  2. Laboratory of Metabolic Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    T. S. Boer, A. van Assen, T. Bos, K. E. Niezen-Koning & D.-J. Reijngoud

  3. Laboratory of Genetic Metabolic Diseases, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands

    J. Ruiter, H. R. Waterham & R. J. A. Wanders

  4. Groningen University Institute for Drug Exploration, The Centre for Liver, Digestive and Metabolic Diseases, Research Laboratory of Paediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    T. G. J. Derks, K. E. Niezen-Koning, G. P. A. Smit & D.-J. Reijngoud

  5. Isala Klinieken, Department of Clinical Chemistry, Zwolle, The Netherlands

    J. M. M. Rondeel

  6. Diagnostic Laboratory for Infectious Diseases and Perinatal Screening, National Institute for Public Health, Bilthoven, The Netherlands

    J. G. Loeber

  7. Department of Clinical Genetics and Human Genetics, VU University Medical Center Amsterdam, Amsterdam, The Netherlands

    L. P. ten Kate

Authors
  1. T. G. J. Derks
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  2. T. S. Boer
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  3. A. van Assen
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  4. T. Bos
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  5. J. Ruiter
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  6. H. R. Waterham
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  7. K. E. Niezen-Koning
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  8. R. J. A. Wanders
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  9. J. M. M. Rondeel
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  10. J. G. Loeber
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  11. L. P. ten Kate
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  12. G. P. A. Smit
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  13. D.-J. Reijngoud
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Corresponding author

Correspondence to T. G. J. Derks.

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Communicating editor: Bridget Wilcken

Competing interests: None declared

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Derks, T.G.J., Boer, T.S., van Assen, A. et al. Neonatal screening for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency in The Netherlands: The importance of enzyme analysis to ascertain true MCAD deficiency. J Inherit Metab Dis 31, 88–96 (2008). https://doi.org/10.1007/s10545-007-0492-3

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  • DOI: https://doi.org/10.1007/s10545-007-0492-3

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