Clinical and genetic spectrum of pediatric primary immunodeficiency diseases at King Fahad Medical City in Saudi Arabia: a Tertiary care center-based study

<title>Abstract</title> <p>Background. Primary immunodeficiency diseases, also called inborn errors of immunity, are monogenic disorders that disproportionately affect populations with high consanguinity. Contemporary pediatric registry data from Saudi tertiary centres other than the main national reference hospital remain limited. Methods. We retrospectively studied all patients evaluated for an inborn error of immunity at King Fahad Medical City, Riyadh, between January 2017 and December 2023. Diagnosis was confirmed mainly by genetic testing or otherwise by clinical diagnosis with supportive immunological work-up. Clinical, genetic, treatment, and outcome data were extracted from the electronic medical records. Predictors of mortality were examined with univariable and multivariable logistic regression. Results. Of 176 records screened, 146 met the inclusion criteria. The median current age of our cohort was 5.5 years and 51.4% were male. Parental consanguinity was reported in 79.5% of families with available data. Combined immunodeficiencies (CID) made up 36.3% of the cohort and combined immunodeficiencies with syndromic features a further 20.5%. A causative gene was identified in 74.7% of patients, most often ATM, RAG1, and ADA2. Mortality among the 97 patients with a documented outcome was 20.6% and was higher in patients with severe CID (SCID) than in others, at 54.2% compared with 9.6%. SCID was the only independent predictor of mortality on multivariable analysis, with an adjusted odds ratio of 7.55 (CI: 1.55–36.72, P = 0.012). Conclusions. Pediatric inborn errors of immunity in our centre were dominated by CID in a highly consanguineous population, with a high rate of genetic confirmation and a concentration of mortality in SCID. These findings, which are broadly consistent with reports from neighbouring countries, support broad early genetic testing, wider newborn screening for SCID, and structured genetic counselling.</p>