Severe combined immunodeficiency (SCID) in Canadian children: a national surveillance study

Jacob Rozmus, Anne Junker, Melanie Laffin Thibodeau, Danielle Grenier, Stuart E Turvey, Wadieh Yacoub, Joanne Embree, Elie Haddad, Joanne M Langley, Rose Marie Ramsingh, Veeran-Anne Singh, Richard Long, Kirk R Schultz, Jacob Rozmus, Anne Junker, Melanie Laffin Thibodeau, Danielle Grenier, Stuart E Turvey, Wadieh Yacoub, Joanne Embree, Elie Haddad, Joanne M Langley, Rose Marie Ramsingh, Veeran-Anne Singh, Richard Long, Kirk R Schultz

Abstract

Purpose: Severe Combined Immune Deficiency (SCID) is universally fatal unless treated with hematopoietic stem cell transplantation (HSCT). Following the identification of disseminated Bacille Calmette-Guérin (BCG) infections in Canadian First Nations, Métis and Inuit (FNMI) children with unrecognized primary immune deficiencies, a national surveillance study was initiated in order to determine the incidence, diagnosis, treatment and outcome of children with SCID in Canada.

Methods: Canadian pediatricians were asked to complete a monthly reporting form if they had seen a suspected SCID case, from 2004 to 2010, through the Canadian Paediatric Surveillance Program (CPSP). If the case met CPSP SCID criteria, more detailed data, including demographics and clinical information about investigations, treatment and outcome was collected.

Results: A total of 40 cases of SCID were confirmed for an estimated incidence of SCID in non-FNMI Canadian children of 1.4 per 100,000 live births (95 % CI 1 to 1.9/100,000). The proportion of SCID cases that were FNMI (17.5 %) was almost three times higher than was expected on the basis of proportion of the pediatric population estimated to be FNMI (6.3 %) resulting in an estimated incidence of 4.4 per 100,000 live births (95 % CI 2.1 to 9.2/100,000) in FNMI Canadian children. The mean age at diagnosis for all SCID cases was 4.2 months (range 1–583 days). There were 12 deaths (30 %; 95 % CI 18–46 %); seven died of confirmed or suspected infections before they could receive an HSCT.

Conclusions: The frequency of SCID cases in FNMI children is higher than in the general Canadian pediatric population. The high mortality rate, due primarily to infection, suggests that early diagnosis by newborn screening followed by HSCT could significantly benefit children with SCID.

References

    1. Sponzilli I, Notarangelo LD. Severe combined immunodeficiency (SCID): from molecular basis to clinical management. Acta Biomed. 2011;82(1):5–13.
    1. Deeks SL, Clark M, Scheifele DW, et al. Serious adverse events associated with bacille Calmette-Guérin vaccine in Canada. Pediatr Infect Dis J. 2005;24(6):538–541. doi: 10.1097/01.inf.0000164769.22033.2c.
    1. Dawar M, Clark M, Deeks SL, et al. A fresh look at an old vaccine: does BCG have a role in 21st century Canada? Int J Circumpolar Health. 2004;63(Suppl 2):230–236.
    1. Ugnat AM, Grenier D, Thibodeau ML, et al. The Canadian paediatric surveillance program: celebrating 15 years of successful paediatric surveillance. Paediatr Child Health. 2011;16(4):203–205.
    1. . Accessed 10 July 2013.
    1. Conley M, Notarangelo L, Etzioni A, Representing PAGID, Pan-American Group for Immunodeficiency, and ESID, European Society for Immunodeficiencies Diagnostic criteria for primary immunodeficiencies. Clin Immunol. 1999;93(3):190–197. doi: 10.1006/clim.1999.4799.
    1. Al-Herz W, Bousfiha A, Casanova JL, et al. Primary immunodeficiency diseases: an update on the classification form the international union of immunological societies expert committee for primary immunodeficiency. Front Immunol. 2011;2:54. doi: 10.3389/fimmu.2011.00054.
    1. Statistics Canada. Table 102-4509 - Live births, by birth weight and sex, Canada, provinces and territories, annual, CANSIM (database)
    1. Statistics Canada. Aboriginal identity population by age groups, median age and sex, 2006 counts for both sexes, for Canada, provinces and territories - 20 % sample data (table). 2006. (accessed September 24, 2013).
    1. Adeli MM, Buckley RH. Why newborn screening for severe combined immunodeficiency is essential: a case report. Pediatrics. 2010;126(2):e465–e469. doi: 10.1542/peds.2009-3659.
    1. Chan K, Puck JM. Development of population-based newborn screening for severe combined immunodeficiency. J Allergy Clin Immunol. 2005;115(2):391–398. doi: 10.1016/j.jaci.2004.10.012.
    1. Stephan JL, Vlekova V, Le Deist F, et al. Severe combined immunodeficiency: a retrospective single-center study of clinical presentation and outcome in 117 patients. J Pediatr. 1993;123(4):564–572. doi: 10.1016/S0022-3476(05)80951-5.
    1. Li L, Moshous D, Zhou Y, et al. A founder mutation in Artemis, an SNM1-like protein, causes SCID in Athabascan-speaking Native Americans. J Immunol. 2002;168(12):6323–6329.
    1. . BCG Vaccine Usage in Canada - Current and Historical - Tuberculosis Prevention and Control - PHAC. 2012. [online] Available at: [Accessed: 7 Jan 2013].
    1. Buckley RH, Schiff SE, Schiff RI, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999;340(7):508–516. doi: 10.1056/NEJM199902183400703.
    1. Brown L, Xu-Bayford J, Allwood Z, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117(11):3243–3246. doi: 10.1182/blood-2010-08-300384.
    1. Puck JM. Laboratory technology for population-based screening for severe combined immunodeficiency in neonates: the winner is T-cell receptor excision circles. J Allergy Clin Immunol. 2012;129(3):607–616. doi: 10.1016/j.jaci.2012.01.032.
    1. Kwan A, Church JA, Cowan MJ, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years. J Allergy Clin Immunol. 2013;132(1):140–150. doi: 10.1016/j.jaci.2013.04.024.
    1. Chan K, Davis J, Pai SY, et al. A Markov model to analyze cost-effectiveness of screening for severe combined immunodeficiency (SCID) Mol Genet Metab. 2011;104(3):383–389. doi: 10.1016/j.ymgme.2011.07.007.
    1. Buckley RH, Schiff SE, Schiff RI, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130(3):378–387. doi: 10.1016/S0022-3476(97)70199-9.
    1. Dvorak CC, Cowan MJ, Logan BR, et al. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. J Clin Immunol. 2013 Jul 2. [Epub ahead of print].

Source: PubMed

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