Scripties UMCG - Rijksuniversiteit 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.





ID 3402
Moeder ID 3084
Volgorde Kuijpers, M.M.
Naam KuijpersMM
Publiceren yes
OAI-naam Student_thesis
Path root/geneeskunde/2016/KuijpersMM/
Gemaakt op: 2017-05-22 07:28:51
Gemodificeerd op: 2017-05-22 07:28:51
Digitaal ID 5922933389013
Afstudeerrichting opleiding/afstudeerrichting 1
Studierichting Studierichting 1
Titel Neonatal bloodspot screening for Medium-Chain Acyl-CoA dehydrogenase deficiency: evaluation of different screening parameters.
Ruilverkeer mogelijk no
Printen in opdracht no
Aantal pagina's 35
Publicatiejaar 2016
Taal en
Engelse samenvatting 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.
Nederlandse samenvatting Achtergrond: Vroege diagnose van Middellange keten acyl-Coenzyme A-dehydrogenase (MCAD) deficiëntie door de neonatale hielprikscreening en behandeling verminderde de morbiditeit en mortaliteit significant. De hielprikscreening ontdekt echter ook fout-positieven (FP) en patiënten met ‘milde’ MCAD deficiëntie. In dit onderzoek zochten we uit of additionele parameters de hielprikscreening zouden kunnen optimaliseren, het aantal FP verminderen en onderscheid maken tussen ernstige en ‘milde’ MCAD deficiëntie.
Methode: een retrospectief onderzoek van de hielprikscreening voor MCAD deficiëntie is uitgevoerd in het Nederlandse geboortecohort 2007-2015. De screeningparameters C8, C6, C10, C10:1 en ratio’s C8/C10 en C8/C2 zijn geëvalueerd op basis van genotypen en MCAD enzym activiteit. In dit onderzoek werd ‘milde’ MCAD deficiëntie gedefinieerd door ‘variante’ genotypen (genotypen die nooit geïdentificeerd waren in patiënten die zich klinisch hadden gepresenteerd) en/of een hoge MCAD enzymactiviteit (≥10%, gemeten in lymfocyten of leukocyten.
Resultaten: In dit onderzoek waren 194 patiënten met MCAD deficiëntie geïdentificeerd, waarvan 189 door de hielprikscreening. De prevalentie was 1/8.288 (95% betrouwbaarheidsinterval: 1/7.265 – 1/9.645). De C8 afkapgrens liet een sensitiviteit van 99% en specificiteit van ongeveer 100% zien. De ratio’s C8/C10 en C8/C2 correleerden ook sterk met MCAD deficiëntie. Een combinatie van de drie screeningparameters verminderde het aantal FP met 70%, maar ook het aantal ‘milde’ MCAD deficiënte patiënten met 22%. De ratio C8/C10 differentieerde, beter dan C8 en C8/C2, tussen ernstige en ‘milde’ MCAD deficiëntie.
Conclusie: Deze studie bevestigd dat de primaire screeningmarker C8 zeer effectief is in het detecteren van MCAD deficiëntie. Echter, toevoeging van de ratio’s C8/C10 en C8/C2 zou de hielprikscreening nog verder verbeteren.
Onderwijsinstelling Medical Sciences
Type embargo abstract openbaar, scriptie op aanvraag
Auteur(s) Kuijpers, M.M.
UMCG begeleider(s) Name supervisor:; Derks, dr. T.G.J.; Department of Metabolic Diseases, Beatrix Children’s Hospita
Auteur(s) Kuijpers, M.M.
UMCG begeleider(s) Name supervisor:; Derks, dr. T.G.J.; Department of Metabolic Diseases, Beatrix Children’s Hospita


 
To top