Chronic granulomatous disease with partial deficiency of cytochrome b558 and incomplete respiratory burst: variants of the X-linked, cytochrome b558-negative form of the disease

Abstract

Five male patients from four different families presented with a clinical record of chronic granulomatous disease (CGD): recurrent infections of the skin and/or respiratory tract with catalase-positive microorganisms, sometimes in combination with granulomata and/or abscesses in various organs. These patients differed from “classical” forms of the disease in that their neutrophils, although deficient in killing in vitro of Staphylococcus aureus, contained a decreased but measurable amount of cytochrome b ₅₅₈ (10–60% of normal on a heme basis), causing weak staining in the nitroblue tetrazolium dye test and a depressed respiratory burst after contact of the cells with fluid or particulate activators of the NADPH:O₂ oxidoreductase. In the cell-free activation system, the defect in the patients' cells was localized in the membrane fraction. In each of the four families, the cellular abnormalities showed an X-linked inheritance. Fusion experiments performed with the monocytes from these patients and those from patients with classical X-linked, cytochrome b ₅₅₈–negative (Xb⁰) or autosomal, cytochrome b ₅₅₈–positive (Ab⁺) CGD showed complementation of NADPH:O₂ oxidoreductase activity in the latter but not in the former combination. Thus, the unusual CGD patients represent variant forms of Xb⁰ CGD, with mutations in the gene coding for the beta subunit of cytochrome b ₅₅₈ that do not cause complete loss of this protein.