Question 1 · Hard
The mother of a 3-year-old boy with X-linked chronic granulomatous disease is tested. She has recurrent mouth ulcers and a photosensitive discoid rash but has never had a serious infection. Her neutrophil count and morphology are normal. In the dihydrorhodamine (DHR) flow test after PMA stimulation, her neutrophils form two distinct populations: 38% with a normal bright fluorescence shift and 62% with no shift at all. A healthy control tested in parallel shows a single bright population. The best interpretation is:
- AAutosomal recessive CGD
- BFailed PMA stimulation
- CMyeloperoxidase deficiency
- DX-linked CGD carrier state
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Answer: D · X-linked CGD carrier state
In X-linked CGD the defective gene (CYBB, coding gp91phox of NADPH oxidase) is on the X chromosome. In a carrier woman, random X inactivation leaves one population of neutrophils using the normal X and another using the mutant X, so the DHR test shows two separate populations, one with a normal respiratory burst and one with none. Carriers with a fair proportion of normal cells rarely have serious infections, but mouth ulcers and lupus-like skin lesions are more common, and carriers with very few normal cells can have CGD-type infections. Autosomal recessive CGD, such as p47phox deficiency, gives a single population with little or no shift rather than two distinct populations. Myeloperoxidase deficiency can blunt the DHR signal in all cells, and the healthy control and her normal population show that the stimulation worked.
- A: Autosomal recessive CGD gives one population with little or no shift, not two distinct populations.
- B: The control and her 38% normal population show that the stimulation worked.
- C: MPO deficiency would blunt the signal in all neutrophils, not leave a normal population.