Diagnosis of Chronic Granulomatous Disease: Strengths and Challenges in the Genomic Era
Document Type
Article
Publication Date
8-1-2024
Abstract
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.
Keywords
inborn errors of immunity (IEI), chronic granulomatous disease (CGD), NADPH oxidase, nitroblue tetrazolium (NBT), dihydrorhodamine (DHR), genetic testing, genomic testing, screening
Divisions
ummc
Funders
National Institute for Health and Care Research (NIHR), UK (ACF-2022-25-003)
Publication Title
Journal of Clinical Medicine
Volume
13
Issue
15
Publisher
MDPI
Publisher Location
ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND