Glucose-6-phosphate dehydrogenase (G6PD) is a key
enzyme in the
pentose phosphate pathway that ensures sufficient
production of
coenzyme nicotinamide adenine dinucleotide phosphate (
NADPH) by catalyzing the reduction of
NADP-F to
NADPH. Noteworthy, the latter mediates the
production of
reactive oxygen species (ROS) by
phagocytic cells such as
neutrophils and
monocytes. Therefore,
patients with severe forms of
G6PD deficiency may present impaired
NADPH oxidase activity and become susceptible to
recurrent infections. This fact, highlights the importance to characterize the immunopathologic mechanisms underlying the susceptibility to
infections in
patients with
G6PD deficiency. Here we
report the first two cases of
G6PD deficiency with Bacille Calmette-Guerin (
BCG) adverse effect, besides
jaundice, hemolytic anemia and
recurrent infections caused by
Staphylococcus aureus. The qualitative G6PD
screening was performed and followed by
oxidative burst analysis using
flow cytometry. Genetic and in silico analyses were carried out by Sanger sequencing and
mutation pathogenicity predicted using
bioinformatics tools, respectively. Activated
neutrophils and
monocytes from
patients displayed impaired
oxidative burst. The genetic
analysis revealed the novel
missense mutation c.1157T>A/p.L386Q in G6PD. In addition, in silico
analysis indicated that this
mutation is pathogenic, thereby hampering the
oxidative burst of
neutrophils and
monocytes from
patients. Our data expand the clinical and genetic spectrum of
G6PD deficiency, and suggest that impaired
oxidative burst in this severe primary immune deficiency is an underlying immunopathologic mechanism that predisposes to mycobacterial
infections.