Case Report : Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G 6 PD A-[ version 1 ; referees : 2 approved with reservations ]

We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A( ) allele. PNH is associated with one or more clones of cells that lack G6PDAcomplement inhibition due to loss of function somatic mutations in the PIGA gene. encodes the enzyme phosphatidylinositol glycan anchor PIGA biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol ( ) anchor synthesis. Two GPI anchored red GPI cell surface antigens regulate complement lysis. G6PD catalyses the first step of the pentose phosphate pathway and enzyme variants, frequent in some populations have been because they confer resistance to malaria, are associated with hemolysis in the presence of oxidizing agents including several drugs. The patient had suffered a hemolytic attack after taking Bactrim, a drug that precipitates hemolysis in G6PD deficient individuals. Since both and G6PD are X-linked we hypothesized that the PIGA mutation was on the PIGA X-chromosome carrying the G6PDAallele. Investigations showed that in fact the PIGA mutation was on the X-chromosome carrying the normal G6PD B allele. We speculate that complement activation on G6PD Ared cells exposed to Bactrim might have triggered complement activation inducing the lysis of G6PD B PNH Type II red blood cells or that the patient may have had a PNH clone expressing G6PDAat the time of the hemolytic episode. 1 1 1