Diverse clinical features and diagnostic delay in monogenic inborn errors of immunity: A call for access to genetic testing

• Published in: Pediatric allergy and immunology 2021-11, Vol.32 (8), p.1796-1803
• Main Authors: Branch, Anna, Modi, Bhavi, Bahrani, Bahar, Hildebrand, Kyla J., Cameron, Scott B., Junker, Anne K., Turvey, Stuart E., Biggs, Catherine M., Candotti, Fabio
• Format: Article
• Language: English
• Subjects: Cohort analysis; cohort studies; Delayed Diagnosis; Diagnosis; Genetic screening; Genetic Testing; High-Throughput Nucleotide Sequencing; Humans; Immune System; Immune System Diseases; immunologic deficiency syndromes; Medical diagnosis; Morbidity; Patients; Phenotyping; primary immunodeficiency diseases; whole exome sequencing
• ISSN: 0905-6157; 1399-3038
• DOI: 10.1111/pai.13571

Background Inborn errors of immunity (IEIs) are a group of conditions affecting immune system development and function. Due to their clinical heterogeneity and lack of provider awareness, patients suffer from long diagnostic delays that increase morbidity and mortality. Next‐generation sequencing facilitates earlier diagnosis and treatment of IEIs, but too often patients are unable to see the benefit of this technology due to gaps in providers’ knowledge regarding which patients to test and barriers to accessing sequencing. Methods Here, we provide detailed clinical phenotyping and describe the impact of genetic sequencing on a cohort of 43 patients with monogenic IEIs seen in a tertiary care center from 2014 to 2019. Data were ed from a chart review, and a panel of clinical immunologists were consulted on the impact of genetic sequencing on their patients. Results We found that our patients had significant diagnostic delays, averaging 3.3 years; had diverse manifestations of immune system dysfunction; and had demonstrated highly complex medical needs, with on average 7.9 subspecialties involved in their care and 4.9 hospitalizations prior to definitive treatment. Our results also demonstrate the benefits of genetic testing, as it provided the majority of our patients with a diagnosis, and positively impacted their treatment, follow‐up, and prognosis. Conclusion This paper expands the paucity of literature on genetically confirmed IEIs in North America and supports the expansion of access to genetic testing for patients with clinical features suggesting IEI, such as those presented in our cohort.