Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and...

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Veröffentlicht in:Journal of clinical medicine 2024-08, Vol.13 (15), p.4435
Hauptverfasser: O'Donovan, Conor J, Tan, Lay Teng, Abidin, Mohd A Z, Roderick, Marion R, Grammatikos, Alexandros, Bernatoniene, Jolanta
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container_issue 15
container_start_page 4435
container_title Journal of clinical medicine
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creator O'Donovan, Conor J
Tan, Lay Teng
Abidin, Mohd A Z
Roderick, Marion R
Grammatikos, Alexandros
Bernatoniene, Jolanta
description Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, underpinning current methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.
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subjects B cells
Chronic granulomatous disease
Cytochrome
Diagnosis
Diseases
Enzymes
Ethylenediaminetetraacetic acid
Genetic aspects
Genetic screening
Granulomas
Infections
Inflammatory bowel disease
Medical research
Medicine, Experimental
Methods
Microorganisms
Mutation
Neutrophils
Oxidases
Pathophysiology
Physiological aspects
Protons
Quality of life
United Kingdom
Virulence
title Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era
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