Inborn errors of immunity in Canadian First Nations and Nunavut Inuit Children: the tip of the iceberg.

Objectives: Inborn errors of immunity (IEI) are a heterogeneous group of genetic diseases that impact normal immune development and function. Individual IEI are rare, but collectively, can represent an important health burden. Little is known about the types of IEI seen in Canadian First Nations (FN) and Inuit populations. We sought to understand the spectrum of serious IEI in FN and Nunavut Inuit children, as a starting point for improving the awareness of these conditions in the community and for health care workers. Methods: A questionnaire was distributed to participating Canadian pediatric tertiary-care centers. Providers were asked to report cases of confirmed or suspected severe immunodeficiencies seen in FN and Nunavut Inuit children. Results: From 2004 to 2022, IEI were reported in 63 FN and 21 Inuit children by 4 pediatric hospitals across 3 Canadian provinces. The majority of cases were immunodeficiencies affecting cellular and humoral immunity (62% of cases in FN and 57% in Inuit children). IKBKB deficiency, adenosine-deaminase severe combined immune deficiency (SCID), and chronic granulomatous disease were the most common IEI. A wide variety of other IEI was reported, many of which would not be detected by current newborn screening for SCID and for which live-attenuated vaccines would have been contraindicated. Conclusions: IEI occur in FN and Inuit children and may be underrecognized. Better understanding the prevalence of these conditions in specific communities could help inform public health policies including newborn screening and immunization programs and ultimately improve the health of FN and Inuit children in Canada.