Master Theses UMCG - University of Groningen
English | Nederlands

Neonatal bloodspot screening for Medium-Chain Acyl-CoA dehydrogenase deficiency: evaluation of different screening parameters.

(2016) Kuijpers, M.M.

Background: Early diagnosis of Medium-Chain Acyl-Coenzyme A Dehydrogenase (MCAD) deficiency through neonatal bloodspot screening (NBS) and treatment significantly reduce morbidity and mortality. However, the NBS also detects false-positives (FP) as well as patients with ‘mild’ MCAD deficiency. In this study we investigated whether additional parameters could optimize the Dutch NBS, reduce FP and differentiate between severe and ‘mild’ MCAD deficiency.
Methods: A retrospective study of the NBS protocol detecting MCAD deficiency in the Dutch birth cohort between 2007-2015 was performed. The screening parameters C8, C6, C10, C10:1 and ratios C8/C10 and C8/C2 were evaluated in relation to genotypes and MCAD enzyme activity. In this study ‘mild’ MCAD deficiency was defined by ‘variant’ genotypes (genotypes that had not been identified in patients with clinical symptomatology) and/or high residual MCAD enzyme activity (≥10% measured in lymphocytes or leukocytes).
Results: 194 MCAD-deficient patients were identified in this study, of which 189 were detected through NBS. The prevalence of MCAD deficiency was 1/8,288 (95% CI: 1/7,265 – 1/9,645). The C8-cut-off showed a 99% sensitivity and approximately 100% specificity. The ratios C8/C10 and C8/C2 also correlated strongly with MCAD deficiency and combining the three parameters reduces the number of FP with 70%, at the expense of 22% of the ‘mild’ MCAD deficient patients. The C8/C10-ratio differentiated better than C8 and C8/C2 between severe and ‘mild’ MCAD deficiency.
Conclusion: This study confirms that the primary screening marker C8 is extremely effective to detect MCAD deficiency. Though, adding the ratios C8/C10 and C8/C2 would further improve the NBS protocol.

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