Self-reported Clinical Outcomes and Quality of Life in Agammaglobulinemia: the Importance of an Early Diagnosis

Abstract

B-lymphocyte deficiencies; Inborn errors of immunity; Newborn screening

Deficiències de limfòcits B; Errors congènits de la immunitat; Cribratge neonatal

Deficiencias de linfocitos B; Errores congénitos de la inmunidad; Cribado neonatal

Purpose Patients with (X-linked) agammaglobulinemia (XLA) suffer from severe, recurrent infections potentially leading to life-threatening complications such as sepsis, meningoencephalitis and chronic lung disease. Early diagnosis and timely treatment can prevent infections and secondary complications, emphasizing a role for early detection of XLA via newborn screening (NBS). Our international multicenter survey study aimed to evaluate self-reported outcomes and parental perspectives in XLA patients to determine whether an early diagnosis is associated with better quality of life (QoL). Methods QoL-questionnaires included the PedsQL for children and SF-36, CVID_QOL, PADQOL-16 for adults. A new questionnaire was specifically developed for parents about an early diagnosis of XLA. Results In total, 88 adult and 65 pediatric XLA patients, and 69 parents from 14 countries completed the survey. Patients with an early diagnosis reported less severe, recurrent infections and less hospitalization (p < 0.05). QoL was significantly lower in multiple health domains for pediatric and adult patients with a late diagnosis compared to the general population. Patients with an early diagnosis reported similar QoL outcomes compared to the general population. Parents showed immense support for NBS for XLA stating that an early diagnosis prevents emotional insecurity, health damage, unnecessary diagnostics and allows early access to medical care and informed family planning. Conclusion Our study has shown supportive evidence to pursue an early diagnosis of XLA from both a self-reported clinical, health related QoL and parental perspective. The main plea from patients and parents is to achieve an early diagnosis for XLA and severe B-lymphocyte deficiencies with NBS.

This study was financially supported by ZonMw (project number 427002014), the Jeffrey Modell Foundation (C.H.I.L.D.R.E.N. grant 2021), the For Wis(h)dom Foundation (project number FWF/2025/2419) and Takeda Pharmaceuticals International AG (grant number IISR-2021-200128). The fellowship of dr. Jamee was supported by the European Federation of Immunological Societies (EFIS) and the European Academy of Allergy & Clinical Immunology (EAACI). Dr. Bloomfield received honoraria from Takeda. Dr. Gonzalez-Granado is supported by Instituto de Salud Carlos III (ISCIII) through the project FIS-PI21/01642, co-funded by the European Union.