World Primary Immunodeficiency Week: A call for newborn screening

The fourth World Primary Immunodeficiency Week (WPIW, http://www.worldpiweek.org/) will take place from 22–29 April 2014; its main aim, as in previous years, is to increase awareness of primary immunodeficiency (PI) conditions. While in the past these conditions were thought to be rare, it is clear today that this is not the case anymore. A recent article showed that more than six million people around the world could be suffering from PI conditions 1 It should be noted that PIs, which are genetic, are not related to AIDS (acquired immunodeficiency syndrome) which is instead caused by a viral infection (human immunodeficiency virus, HIV). Although it is clear that early diagnosis and treatment of PIs will improve morbidity and mortality, there is one condition in which early diagnosis is a medical paediatric emergency, and this is severe combined immunodeficiency (SCID) 2. Most of these children are born after an uneventful pregnancy and delivery and will only be diagnosed in the first year of life, after suffering from severe infections which unfortunately may lead to death. SCID is not a common condition with an incidence of 1:20 000 – 60 000 depending on the geographic area; in some countries mainly in the Middle East consanguinity is very high and thus the incidence is much higher. However, this may be an underestimate of the true burden of SCID worldwide as many infants die of infections before diagnosis. Nevertheless, it is clear that early diagnosis, before infections occur, is crucial in order to provide proper therapeutic care and hence decrease mortality and morbidity in this group of infants. Several studies have shown that performing hematopoietic stem cell transplantation (HSCT) to SCID children before the age of 3 months has a success rate of 95% as opposed to around 70% if the procedure is done later in life (as reviewed in 3), highlighting the importance of early diagnosis. SCID now fulfills all these criteria, including a testing fulfilling point (v) above as reviewed by Jennifer Puck 4. Using standard Guthrie paper spotted with a whole blood sample, one can extract DNA and look for a DNA biomarker of normal T-cell development, T-cell receptor excision circles (TRECs), which would be absent in SCID patients. One can also apply kappa deleting recombination excision circles (KRECs) to the same sample and detect cases of congenital hypogammaglobulinemia states, another PI. The TREC technique is very accurate. False positive results, mainly caused by TREC amplification failures in non-immunodeficient newborns, have been reported to occur in less than 0.008% tests (a level similar to that for other newborn screening procedures) 5, and it should be noted that most of these false positive cases were in preterm babies weighting less than 1500 g. Furthermore, the cost of the screening is balanced by the significantly higher difference in the high costs of haematopoietic stem cell transplantation (HSCT) of SCID patients when performed later than three months of age than at an earlier stage following NBS screening. After several pilot studies 4, which indeed proved that NBS for SCID fulfills all the Wilson and Jungner criteria, several states in the USA and the province of Ontario, Canada have incorporated TREC testing as part of their newborn screening panels. So far more than one million newborns have been screened and all cases of SCID detected have been successfully treated by HSCT! This situation, however, is not representative of the global picture. In Africa, for example, neonatal screening for SCID is urgently required as access to care, and hence treatment of infections, is very limited. Nonetheless, the situation in many African countries is problematic as the classical Guthrie test, i.e. the test used to identify e.g. elevated levels of phenylalanine (phenylketonuria) in newborns, is not yet implemented there. In contrast to the situation in the US and Ontario, Canada, none of the nations in Europe have yet implemented SCID NBS program although committees in some of the European countries e.g. France, England and Germany, are thoroughly discussing the addition of this to their national NBS programme. Progress is further forward in Mexico and Brazil where TREC screening is in an advanced state of implementation. With WPIW on the horizon, we call on all countries around the world to take actions and to add primary immunodeficiency NBS to their respective programmes and thus save the lives of children with this devastating disease, a disease which, if identified early, can be cured, leading to a long-standing healthy and productive life.

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