**9. Some genetic diseases particularly relevant in the erythrocyte context**

Glucose-6-phosphate dehydrogenase is an enzyme in the glycolysis and pentose phosphate pathways. Its deficiency particularly effects the erythrocyte since the erythrocyte depends on glycolysis and the pentose phosphate pathway for its energy needs. Erythrocyte irregularities called Heinz bodies are frequent in glucose-6-phosphate deficiency. The deficiency is particularly common in sub-Saharan Africa due to a survival advantage in malaria-afflicted areas. Interestingly, deficiency for glucose-6-phosphate dehydrogenase seems to be associated with hemolysis in Covid-19 patients [126]. Patients with glucose-6-phosphate deficiency may react with hemolysis as a response also to other infections and treatment with primaquine or hydroxychloroquine [127, 128], suggesting a more general susceptibility to hemolysis associated with glucose-6-phosphate deficiency. Some other diseases involving the erythrocyte are sickle-cell disease, thalassemia, stomatocytosis, spherocytosis, ovalocytosis, paroxysmal nocturnal hemoglobinuria (PNH), polycythemia vera, acute erythroid leukemia and lecithin-cholesterol acyltransferase deficiency (LCAT). Paroxysmal nocturnal hemoglobinuria (PNH) is an intravascular hemolytic anemia, most often caused by somatic mutations in the gene encoding phosphatidylinositol glycan A (PIGA), leading to dysfunctional GPI-dependent anchoring of membrane proteins. One such erythrocyte membrane protein is decay accelerating factor (DAF) which acts to limit action of the alternative complement pathway. The resulting complement-driven hemolysis can be counteracted by the humanized monoclonal antibody eculizumab directed against terminal complement component C5.
