Biochemical defects in paroxysmal nocturnal hemoglobinuria (PNH) are often associated with genetic mutations, particularly with blocked synthesis of glycosylphosphatidylinositol (GPI) anchors. Since the GPI anchor is located on the X chromosome, and the X chromosome is often inactivated in female somatic cells, only one mutation is required to eliminate the expression of GPI-related proteins in either males or females. This genetic mechanism is closely related to the pathogenesis of PNH.
In patients with PNH, the majority of type II PNH cells (complete lack of GPI-related proteins) are due to frame shift mutations that occur in early hematopoietic progenitor cells. This mutation causes the same mutation to occur in all blood cell lines, further affecting the structure and function of the cell membrane.
This link between genetic and biochemical defects provides us with more insight into the pathogenesis of PNH. Understanding these mechanisms can help develop more effective diagnostic and optimal methods and improve patients' quality of life. Several complement inhibitors have been approved for PNH, but these drugs do not alter the underlying defects of the disease and therefore need to be continued. Allogeneic hematopoietic stem cell transplantation is a potential method, but requires the identification of a histologically compatible donor and is associated with significant morbidity and mortality.
More research is needed to better understand the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH) and to develop more effective methods. By delving into the role of gene mutations, cell membrane structure and function, and the complement system, we can better provide patients with personalized programs that improve their quality of life and reduce morbidity and mortality.