Newborn screening for severe combined immunodeficiency—Coming to a region near you soon

The most profound of primary immunodeficiencies, severe combined immunodeficiency (SCID), presents in infancy. Infants appear healthy at birth, but they are unable to clear pathogens, particularly viruses, and present with recurrent infection, progressive pnueumonitis and failure to thrive due to enteric viral infection, often associated with persistent vaccine-strain rotavirus. The administration of live vaccines is contraindicated in these infants, but most who are eligible receive bacillus Calmette–Guérin vaccination and the live rotavirus vaccine before the diagnosis of SCID is made, making treatment more complicated. Newborn infants with SCID can be screened using the newborn bloodspot to measure T lymphocyte receptor excision circles (TRECs), episomal DNA formed during T lymphocyte receptor development and very low or absent in SCID. Introduction of this programme in the United Kingdom will require the neonatal BCG vaccination programme to be altered, with vaccination at 28 days, once the SCID screening result is known. Although SCID newborn screening has been successfully introduced in other countries, the change in neonatal BCG vaccination requires the introduction of newborn screening to be carefully introduced. An evaluation of impact of screening on SCID diagnosis, treatment and outcomes, together with an evaluation of the technology used to detect TRECs, and the impact of screening and changes to the BCG programme on families will commence in six screening regions in England in September 2021 for 2 years – should the evaluation prove positive, it is likely that screening for this fatal disease will be introduced across the United Kingdom.