Health-Related Quality of Life (HRQOL) in Pediatric and Adult Patients with X-Linked Hyper IgM

Background X-linked hyper IgM syndrome (XHIGM) is a rare primary immunodeficiency (PID) caused by pathogenic variants in the CD40 ligand (CD40LG) gene, resulting in defective immunoglobulin class-switch recombination, causing recurrent infections and malignancy. Treatment includes prophylactic antimicrobials, gammaglobulin replacement therapy (IGRT), and hematopoietic cell transplantation (HCT). To date, the impact of XHIGM on perceived quality of life has not been examined. The purpose of this study was to evaluate health-related quality of life (HRQoL) in individuals with XHIGM using validated Patient-Reported Outcomes Measurement Information System (PROMIS) instruments. Methods We conducted a prospective cross-sectional study of individuals self-identified as having XHIGM. Participants/caregivers completed REDCap surveys, including age-appropriate PROMIS HRQoL instruments in English or Spanish. Raw scores were converted to standardized T-scores (mean = 50, SD = 10) using standard reference data. A 3-point T-score difference was considered clinically meaningful. Statistical comparisons were performed using Kruskal–Wallis and Fisher’s exact tests. Results Of 89 respondents, 63 (52 English and 11 Spanish) provided analyzable data (mean age 17.5 years, range 5–52; median age at diagnosis 13.0). 59% were post-HCT. 60% were receiving IGRT: 100% of non-transplanted respondents and 32% of post-HCT respondents. Three patients were diagnosed with malignancy; two were diagnosed after HCT. Compared to the general population, adult respondents reported worse global mental health, greater anxiety and depression, and reduced physical function. Proxy and pediatric self-reports indicated worse global health and reduced mobility (self-reports only). Compared to the general population, transplanted adults not receiving IGRT reported increased global physical health, physical function, and social participation. Transplanted pediatric respondents not receiving IGRT reported decreased depression, fatigue, and pain interference. Adult, pediatric, and parent proxy reports for those transplanted and still receiving IGRT reported worse HRQoL compared to the general population in more domains (8 of 9 adult, 5 of 9 pediatric, and 3 of 7 proxy domains) than any other treatment group. Conclusions Persons with XHIGM experience meaningful impairments in HRQoL. Those requiring IGRT after undergoing HCT reported worse HRQoL in more domains than the other treatment groups.