Chronic granulomatous disease in two sisters

Two sisters with chronic granulomatous disease (CGD) have been studied. The diagnosis was suggested by the histopathological findings from the spleen and lymph nodes of the proband and confirmed by the low values obtained in the following tests performed on polymorphonuclear leukocytes (PMN): chemiluminescence, nitroblue tetrazolium (NBT) reduction, killing of Staphylococcus aureus, and O2- production. NADPH oxidase activity was not detected in the homogenates of the patients' PMN but cytochrome b was normally present. In addition, PMN depolarization induced by phorbol-myristate acetate was absent, thus suggesting a defect of the activation mechanism of the respiratory enzyme. The normal depolarization induced by ouabain indicated that the membrane polarity regulated by the Na/K pump in the patients' cells was not affected. The low, but not completely absent, respiratory activity of the patients' PMN could suggest an X-linked mode of inheritance with incomplete Lyonization. From a clinical point of view, one sister had mild symptoms whereas the other was almost symptomless, thus confirming once more the heterogeneity of CGD syndrome.