Molecular diagnosis of chronic granulomatous disease
1Deptartment of Blood Cell Research, Sanquin Blood Supply Organization, Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Abstract:
Patients with chronic granulomatous disease (CGD) suffer from recurrent, life-threatening bacterial and fungal infections of the skin, the airways, the lymph nodes, liver, brain and bones. Frequently found pathogens are Staphylococcus aureus, Aspergillus species, Klebsiella species, Burkholderia cepacia and Salmonella species. CGD is a rare (∼1:250 000 births) disease caused by mutations in any one of the five components of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in phagocytes. This enzyme generates superoxide and is essential for intracellular killing of pathogens by phagocytes. Molecular diagnosis of CGD involves measuring NADPH oxidase activity in phagocytes, measuring protein expression of NADPH oxidase components and mutation analysis of genes encoding these components. Residual oxidase activity is important to know for estimation of the clinical course and the chance of survival of the patient. Mutation analysis is mandatory for genetic counselling and prenatal diagnosis. This review summarizes the different assays available for the diagnosis of CGD, the precautions to be taken for correct measurements, the flow diagram to be followed, the assays for confirmation of the diagnosis and the determinations for carrier detection and prenatal diagnosis.
Insights
Chronic granulomatous disease (CGD) is a rare genetic disorder affecting phagocyte function. Diagnosis involves assessing NADPH oxidase activity and genetic mutations for proper patient management and genetic counseling.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Chronic granulomatous disease (CGD) causes severe, recurrent infections due to impaired phagocyte function.
- It results from mutations in NADPH oxidase components, crucial for pathogen killing.
- Common pathogens include Staphylococcus aureus and Aspergillus species.
Purpose of the Study:
- To review diagnostic assays for CGD.
- To outline precautions for accurate testing.
- To provide guidance on genetic counseling and prenatal diagnosis.
Main Methods:
- Measuring phagocyte NADPH oxidase activity.
- Assessing protein expression of NADPH oxidase components.
- Performing gene mutation analysis.
Main Results:
- Residual oxidase activity correlates with clinical outcomes and survival.
- Mutation analysis is essential for genetic counseling and prenatal diagnosis.
- Various assays are available for diagnosis, confirmation, and carrier detection.
Conclusions:
- Accurate molecular diagnosis of CGD is vital for patient care.
- Understanding NADPH oxidase function and genetic basis is key.
- Comprehensive diagnostic strategies aid in management and family planning.
