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.

Centre for Inborn Errors of Immunity Department of Pediatrics Department of Clinical Immunology and Allergology Jessenius Faculty of Medicine in Martin Comenius University in Bratislava University Hospital in Martin Martin Slovakia

Department of Children's Diseases and Pediatric Surgery 1 Horbachevsky Ternopil National Medical University Ternopil Ukraine

Department of Immunology Children's Memorial Health Institute Warsaw Poland

Department of Immunology Motol University Hospital and 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Infectious Diseases Amsterdam UMC Amsterdam the Netherlands

Department of Infectious Diseases Leiden University Medical Center Leiden the Netherlands

Department of Internal Medicine division Clinical and Experimental Immunology Maastricht University Medical Center Maastricht the Netherlands

Department of Internal Medicine division of Allergy and Clinical Immunology Department of Immunology Erasmus University Medical Center Rotterdam Rotterdam the Netherlands

Department of Maternal Infantile and Urological Sciences Sapienza University of Rome Rome Italy

Department of Molecular Medicine Sapienza University of Rome Rome Italy

Department of Paediatric Immunology Rheumatology and Infectious Diseases Emma Children's Hospital Amsterdam University Medical Centres University of Amsterdam Amsterdam the Netherlands

Department of Paediatric Infectious Diseases and Immunology Erasmus MC Sophia Children's Hospital Rotterdam the Netherlands

Department of Pediatric Immunology Ege University Faculty of Medicine Izmir Turkey

Department of Pediatric Infectious Disease and Immunology Amalia Children's Hospital Radboudumc Nijmegen the Netherlands

Department of Pediatrics and Adolescent Medicine St Josef Hospital Braunau Austria

Department of Pediatrics Division of Pediatric Immunology and Stem Cell Transplantation Willem Alexander Children's Hospital Leiden the Netherlands

Department of Pediatrics Laboratory for Pediatric Immunology Willem Alexander Children's Hospital Leiden University Medical Center Albinusdreef 2 Leiden ZA 2333 the Netherlands

Dipartimento di Neuroscienze Riabilitazione Oftalmologia Genetica e Scienze Materno Infantili Università degli Studi di Genova Genoa Italy

Division of Immunology Department of Medical Biochemistry and Biophysics Karolinska Institutet Stockholm Sweden

Great North Children's Hospital Newcastle upon Tyne UK

Immunology lab Belarusian Research Center for Pediatric Oncology Hematology and Immunology Minsk Belarus

Institute of Allergology and Clinical Immunology Faculty of Medicine Charles University and University Hospital in Hradec Kralove Hradec Kralove Czech Republic

Paediatric Department Comenius University Medical Faculty in Bratislava National Institute for Childhood Diseases Bratislava Slovakia

Paediatric Rheumatology and Autoinflammatory Diseases Unit IRCCS Istituto Giannina Gaslini Genoa Italy

Pediatric Infectious Diseases and Immunodeficiencies Unit Children's Hospital Vall d'Hebron Barcelona Hospital Campus Barcelona Catalonia Spain

Primary Immunodeficiencies Unit Department of Pediatrics University Hospital 12 octubre Research Institute imas12 Complutense University School of Medicine Madrid Spain

Primary Immunodeficiency Unit Academic hospital Policlinico Umberto 1 Rome Italy

Research Center for Immunodeficiencies Children's Medical Center Tehran University of Medical Sciences Tehran Iran

Rheumatology and Clinical Immunology University Medical Center Utrecht Utrecht University Utrecht the Netherlands

Sheffield Children's NHS Foundation Trust Sheffield UK

Translational and Clinical Research Institute Newcastle University Newcastle upon Tyne UK

Worcestershire Acute Hospitals NHS Trust Worcester UK

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