Newborn haemoglobinopathy screening using tandem mass spectrometry: Lessons from investigation of an unusual case

Objective England has universal screening for sickle cell disease in newborns, with a policy of reporting beta thalassaemia major where it is detected. We report a case with a high gamma/beta ratio (20.167), but all other tandem mass spectrometry results within expected normal limits. The second test did not support the presumed diagnosis of beta thalassaemia major. As the two results were discrepant, further investigations were carried out. Methods and results Sanger sequencing identified a novel mutation HBB:c.40 G > A (Hb Tower Hamlets) with concomitant beta plus (severe) thalassaemia due to the HBB:c.92 + 5 G > C mutation. Conclusions This case highlights considerations for policy makers and implementers of new methods in screening programmes. For the English screening programme, the importance of adherence to the two-part testing strategy for newborn haemoglobinopathy screening is demonstrated. When discrepancies occur in results between the two tests, a thorough investigation is indicated. Communication, training, incident review and oversight are vital aspects of any screening programme. Protocols, risk assessments and guidance require constant monitoring and review to ensure that they remain fit for purpose. When new methods are introduced, stringent application of these principles is recommended.