Chronic granulomatous disease in an adult female with granulomatous cheilitis. Evidence for an X-linked pattern of inheritance with extreme lyonization.
We describe in this paper a female patient affected by chronic granulomatous disease with all the features of the classic X-linked form of the disease and presenting a mild form of the disease, the major clinical manifestation being a granulomatous cheilitis. The capability of the patient's phagocytes to undergo a respiratory burst in response to different stimuli was markedly depressed and only 10% of the patient's neutrophils were able to reduce nitroblue tetrazolium when stimulated with phorbol myristate acetate to an extent similar to normal cells. With this test, the neutrophils of the patient's mother showed a clear mosaicism, only 40% being able to reduce the dye. Activation of NADPH oxidase in cell-free systems showed that the phagocyte defect was at the level of a membrane component. Difference in spectra revealed that the observed membrane defect was due to a lack of cytochrome b558, the terminal component of NADPH oxidase. Incubation for 2 or 24 h of the patient's neutrophils with human recombinant interferon-gamma and granulocyte macrophage colony-stimulating factor did not correct their defective capability to undergo a respiratory burst However, cultivation of the patient's monocytes with interferon-gamma for prolonged times substantially enhanced their capability to produce hydrogen peroxide.
Dusi
S
S
Institute of General Pathology, University of Verona, Italy.
Poli
G
G
Berton
G
G
Catalano
P
P
Fornasa
C V
CV
Peserico
A
A
D000328:Adult; D002474:Cell-Free System / Q000187:drug effects / Q000201:enzymology; D002613:Cheilitis / Q000097:blood / Q000235:genetics*; D003115:Colony-Stimulating Factors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006099:Granuloma / Q000097:blood / Q000235:genetics*; D006105:Granulomatous Disease, Chronic / Q000097:blood / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000097:blood; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000097:blood; D014960:X Chromosome
D003115:Colony-Stimulating Factors; D006133:Growth Substances; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D010100:Oxygen