The Case for Mandatory Newborn Screening for Severe Combined Immunodeficiency (SCID)

Abstract

Severe combined immunodeficiency (SCID) is the most severe form of inherited primary immunodeficiency and is a paediatric emergency. Delay in recognising and detecting SCID can have fatal consequences and also reduces the chances of a successful haematopoietic stem cell transplant (HSCT). Screening for SCID at birth would prevent children from dying before HSCT can be attempted and would increase the success of HSCT. There is strong evidence to show that SCID fulfills the internationally-established criteria for a condition to be screened for at birth. There is also a test (the T-cell receptor excision circle (TREC) assay) that is now being successfully used in an increasing number of US states to screen for SCID in routine newborn Guthrie samples. Concerted lobbying efforts have highlighted the need for newborn screening (NBS) for SCID, and its implementation is being discussed in Europe both at EU and individual country level, but as yet there is no global mandate to screen for this rare and frequently lethal condition. This paper summarizes the current evidence for, and the success of SCID NBS, together with a review of the practical aspects of SCID testing and the arguments in favour of adding SCID to the conditions screened for at birth.

Primer estudio piloto en España sobre el cribado neonatal de las inmunodeficiencias primarias: TRECS y KRECS identifican linfopenias T y B graves

“…Al determinar TRECS y KRECS simultáneamente en la misma muestra, se aumenta la capacidad diagnóstica de la prueba. Mediante la PCR multiplex (ensayo TRECS/KRECS/ACTB) se identifican, aparte de los déficits congénitos de los linfocitos T clásicos (IDCG), también otros trastornos inmunitarios en neonatos asintomáticos, como por ejemplo las agammaglobulinemias, inmunodeficiencias combinadas y la AT 14,21 . Además, tiene capacidad de detectar a aquellos pacientes con IDCG con un fenotipo menos típico que, ocasionalmente, no son identificados a través de ensayos con determinación aislada de TREC 23 .…”

“…Con estos límites, el 0,75% de las muestras testadas resultaron patológicas en nuestra población. Otros grupos han comunicado cifras de 0,08-4,1%, dependiendo del punto de corte usado 13,20,21 . Estudios poblaciones con un número elevado de muestras patológicas serían inviables, puesto que para nuestra área de salud (25.000 partos/año) esta tasa se traduciría en la necesidad de repetir el ensayo a 188 muestras al año.…”

FOXN1 deficient nude severe combined immunodeficiency

“…Population-based newborn screening (NBS) programmes for SCID have been introduced in several countries [50–52]. Polymerase chain reaction (PCR) on DNA extracted from Guthrie card blood spots is used to quantify circularised DNA by-products generated during TCR formation in the thymus, called T-cell receptor excision circles (TRECs) [53, 54].…”

Current screening approaches for antibody deficiency

“…There is good evidence to support neonatal screening for SCID [23] and successful programmes have been developed in a number of countries [19,20,[24][25][26]. Screening for other immunodeficiencies has not been widely implemented.…”