Case Report: Paroxysmal nocturnal hemoglobinuria in a woman heterozygous for G6PD A-.
We describe a case of paroxysmal nocturnal hemoglobinuria (PNH) in a woman who is heterozygous for the glucose-6-phosphate dehydrogenase A-   ( G6PDA-) allele. PNH is associated with one or more clones of cells that lack complement inhibition due to loss of function somatic mutations in the PIGA gene.  PIGA encodes the enzyme phosphatidylinositol glycan anchor biosynthesis, class A, which catalyses the first step of glycosylphosphatidylinisotol ( GPI)  anchor synthesis. Two GPI anchored red 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 selected 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 co-trimoxazole, a drug that precipitates hemolysis in G6PD deficient individuals. Since both G6PD and PIGA are X-linked we hypothesized that the PIGA mutation was on the X-chromosome carrying the G6PDA- allele. 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 A- red 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 G6PDA- at the time of the hemolytic episode.
Division of Hematology, Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, 19104, USA.
Nieves
N
Perdigones
Division of Hematology, Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, 19104, USA.
Mariela
M
Morales
Division of Hematology, Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, 19104, USA.
Philip
P
Mason
Division of Hematology, Department of Pediatrics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, 19104, USA ; Division of Hematology, University of Pennsylvania School of Medicine, Philadelphia, 19104-4318, USA.
Monica
M
Bessler