Paroxysmal Nocturnal Hemoglobinuria with Glucose-6-Phosphate Dehydrogenase Deficiency: A Case Report and Review of the Literature

Abstract

In this study, we are describing a female patient with paroxysmal nocturnal hemoglobinuria (PNH) and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Both diseases are known to cause hemolytic anemia that mediates the hemolysis of RBCs through several mechanisms. In PNH the hemolysis is mediated through complement activation and oxidative stress. G6PD enzyme is crucial in preventing damage to cellular structures caused by oxygen-free radicles. In G6PD deficiency the hemolysis is mediated through the oxidative stress created by oxygen-free radicles. Since both diseases mediate hemolysis through the oxidative stress, we hypothesize that both conditions have facilitated an effect on each other and this will reflect on the response to treatment, and this response to treatment could vary based on whether the two mutations occurred in the same gene or in two different X chromosomes. Having diagnosed PNH, the management is very expensive and not all the patients can afford it, especially our patient who is a maid by occupation. So, the real challenge in our case is to monitor her in subsequent visits and to plan the treatment keeping in mind her financial status.

Complement-mediated oxidative damage of red cells impairs response to eculizumab in a G6PD-deficient patient with PNH

“…In 1 patient, 21 who was on eculizumab, the very large population of PNH cells expressed the wild-type G6PD allele; the other patient was not on eculizumab. 22 This interaction, which we have observed in vivo and validated in vitro, is novel and has pharmacogenetic implications. G6PD deficiency as such has only a mild impact on the clinical expression of PNH, as complement activation causes hemolysis of PNH RBCs regardless of their G6PD status (supplemental Figure 2A).…”

Dosage Compensation in Females with X-Linked Metabolic Disorders

“…Ultimately, as a result, most heterozygous females exhibit significantly fewer symptoms depending on the XCI pattern [ 188 , 190 ]. Homozygosity for the abnormal G6PD gene does not happen often, and these females are just as severely affected as men [ 193 ].…”

“…In a 31-year-old Filipino woman with dizziness, headache, dyspnea, generalized body edema, and hematuria, G6PD deficiency was diagnosed along with paroxysmal nocturnal hemoglobinuria (PNH) [ 193 ]. It was the third reported case of the coexistence of these two disorders, and the previous two were also women.…”

“…Both PNH and G6PD are very rare, and both are X-linked. What is more, erythrocyte hemolysis occurs in patients suffering from any of the two disorders; however, it is mediated through different mechanisms; thus, the authors of the report discus the facilitating effect of these conditions to each other and the possible effect of the state of dual morbidity on the response to treatment [ 193 ].…”