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.
Agudelo-Flórez
Piedad
P
Center for Investigation in Pediatrics and Department of Pediatrics, State University of Campinas Medical School, Campinas, Brazil.
Costa-Carvalho
Beatriz T
BT
López
Juan Alvaro
JA
Redher
Jussara
J
Newburger
Peter E
PE
Olalla-Saad
Sara Teresinha
ST
Condino-Neto
Antonio
A
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