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

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• 作者：T. G. J. Derks ; T. S. Boer ; A. van Assen ; T. Bos ; J. Ruiter ; H. R. Waterham ; K. E. Niezen-Koning ; R. J. A. Wanders ; J. M. M. Rondeel and J. G. Loeber ; et al.
• 刊名：Journal of Inherited Metabolic Disease
• 出版年：2008
• 出版时间：February, 2008
• 年：2008
• 卷：31
• 期：1
• 页码：88-96
• 全文大小：443.1 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Internal Medicine
  Metabolic Diseases
  Human Genetics
  Biochemistry
  Pediatrics
  
• 出版者：Springer Netherlands
• ISSN：1573-2665

文摘

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 ≥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 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.