Relationship between neonatal screening results by HPLC and the number of a-thalassaemia gene mutations; Consequences for the cut-off value

Objectives: To evaluate the relationship between FAST peak percentage by adapted Bio-Rad Vnbs analysis using the valley-to-valley integration and genotypes with the aim to improve differentiation between severe a-thalassaemia forms (HbH disease) and the milder disease types. Method: DNA analysis for a-thalassaemia was performed on 91 dried blood spot samples presenting normal and elevated FAST peak levels, selected during three years of Dutch national newborn screening. Results: Significant differences were found between samples with and without a-thalassaemia mutations, regardless of the genetic profiles. No significant difference was demonstrated between HPLC in -α/ αα and -α/-α, between -α/-α and - -/αα and between - -/αα and - -/-α genotypes. Conclusion: This study confirms that the percentage HbBart's, as depicted by the FAST peak, is only a relative indication for the number of a genes affected in a-thalassaemia. Based on the data obtained using the modified Bio-Rad Vnbs software, we adopted a cut-off value of 22.5% to discriminate between possible severe a-thalassaemia or HbH disease and other a-thalassaemia phenotypes. Retrospectively, if this cut-off value was utilized during this initial three-year period of neonatal screening, the positive predictive value would have been 0.030 instead of 0.014.

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