Association of glucose-6-phosphate dehydrogenase deficiency and X-linked chronic granulomatous disease in a child with anemia and recurrent infections.
Patients with severe leukocyte G6PD deficiency may present with impairment of NADPH oxidase activity and a history of recurrent infections, mimicking the phenotype of chronic granulomatous disease. We report herein a child with recurrent infections who initially received the diagnosis of G6PD deficiency. His erythrocyte G6PD activity was reduced: 1.8 U/g Hb (normal: 12.1 +/- 2.1 U/g Hb). Further studies revealed that G6PD activity in neutrophils, mononuclear leukocytes, and Epstein-Barr virus-transformed B-lymphocytes from the proband was similar to healthy controls. Molecular studies showed that the G6PD deficiency was due a 202 G-->A mutation, the A- variant common in African ethnic groups. The proband also exhibited severely impaired respiratory burst activity, as observed in X-linked CGD. Sequence analysis of genomic DNA showed a 264 G-->A substitution at the 3' splice junction of gp91-phox exon 3. The cDNA sequence showed a deletion of gp91-phox exon 3, giving rise to an unstable or nonfunctional mutant gp91-phox and to the phenotype of X-linked CGD. We propose that clinicians treating a patient with G6PD deficiency during a severe infection episode consider the possibility of temporary or permanent impairment of the phagocytes' microbicidal activity and the eventual association of G6PD deficiency and chronic granulomatous disease.
Center for Investigation in Pediatrics and Department of Pediatrics, State University of Campinas Medical School, Campinas, Brazil.
Piedad
P
Agudelo-Flórez
Beatriz T
BT
Costa-Carvalho
Juan Alvaro
JA
López
Jussara
J
Redher
Peter E
PE
Newburger
Sara Teresinha
ST
Olalla-Saad
Antonio
A
Condino-Neto
D019943:Amino Acid Substitution; D000740:Anemia / Q000150:complications* / Q000201:enzymology; D001483:Base Sequence; D001773:Blood Cells / Q000201:enzymology; D002648:Child; D004247:DNA / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D015870:Gene Expression; D005954:Glucosephosphate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000235:genetics*; D006105:Granulomatous Disease, Chronic / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D007239:Infections / Q000150:complications* / Q000201:enzymology; D008297:Male; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D013481:Superoxides / Q000378:metabolism
D018076:DNA, Complementary; D013481:Superoxides; D004247:DNA; D005954:Glucosephosphate Dehydrogenase