Adults with chronic granulomatous disease of “childhood”

Abstract

Patients with chronic granulomatous disease of childhood have an inherited defect in polymorphonuclear neutrophil (PMN) bactericidal activity and suffer from recurrent severe infections. The onset is usually in infancy with a fatal outcome nearly always by adolescence. Four adult male siblings, aged 28, 30, 32 and 40 years, had the onset at age six of serious bacterial infections involving the lungs and lymph nodes followed by a marked decrease in the frequency of infections by their mid-twenties. Sequelae include pulmonary fibrosis, ill-defined polyarthritis and glomerulonephritis. The diagnosis of chronic granulomatous disease (CGD) of childhood was made by showing the characteristic defects in PMN function. Despite normal morphology and the ability to ingest microbes, postphagocytic PMN failed to (1) reduce nitroblue tetrazolium (NBT) dye, (2) consume oxygen and produce hydrogen peroxide and (3) stimulate the hexose monophosphate shunt. Family studies demonstrated X-linked recessive inheritance. PMN glucose-6-phosphate dehydrogenase (G-6-PD) levels were normal. Although these oxidative abnormalities of the patients' PMNs were marked and typical of “classic” CGD, patients' PMNs killed and iodinated bacteria slightly better than cells from previously studied patients with CGD. Additional bactericidal mechanisms which might explain the longevity of the patients were searched for in phagocytic cells. To see if nonoxidative bactericidal factors were important, the patients' PMNs were studied anaerobically. However, like normal PMNs, the patients' cells showed impaired bacterial killing anaerobically. In contrast to normal monocytes and cultured macrophages which reduced NBT, patients' cells failed to reduce the dye. CGD should be considered in adults with a history of severe infections and unexplained pulmonary fibrosis.