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. 2021 Nov;32(8):1796-1803.
doi: 10.1111/pai.13571. Epub 2021 Jun 25.

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

Anna Branch  1   2   3 , Bhavi Modi  2   3 , Bahar Bahrani  3   4 , Kyla J Hildebrand  2   3 , Scott B Cameron  2 , Anne K Junker  2 , Stuart E Turvey  2   3 , Catherine M Biggs  2   3
Affiliations

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

Anna Branch et al. Pediatr Allergy Immunol. 2021 Nov.

Abstract

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 abstracted 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.

Keywords: cohort studies; delayed diagnosis; genetic testing; immunologic deficiency syndromes; primary immunodeficiency diseases; whole exome sequencing.

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References

REFERENCES

    1. Turvey SE, Bonilla FA, Junker AK. Primary immunodeficiency diseases: a practical guide for clinicians. Postgrad Med J. 2009;85(1010):660-666. https://doi.org/10.1136/pgmj.2009.080630
    1. Bousfiha A, Jeddane L, Picard C, et al. Human inborn errors of immunity: 2019 update of the IUIS phenotypical classification. J Clin Immunol. 2020;40(1):66-81. https://doi.org/10.1007/s10875-020-00758-x
    1. Ochs HD, Hagin D. Primary immunodeficiency disorders: general classification, new molecular insights, and practical approach to diagnosis and treatment. Ann Allergy, Asthma Immunol. 2014;112(6):489-495. https://doi.org/10.1016/j.anai.2014.04.007
    1. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136(5):1186-1205.e78. https://doi.org/10.1016/j.jaci.2015.04.049
    1. Resnick ES, Bhatt P, Sidi P, Cunningham-Rundles C. Examining the use of ICD-9 diagnosis codes for primary immune deficiency diseases in New York State. J Clin Immunol. 2013;33(1):40-48. https://doi.org/10.1007/s10875-012-9773-1

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