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Definition: Paroxysmal nocturnal hemoglobinuria (PNH) is a disease that results from acquired mutations in the phosphatidylinositol glycan complementation group A gene (PIGA), an enzyme that is essential for the synthesis of certain membrane-associated complement regulatory protein
Typical Clinical Triad: Intravascular hemolysis, Bone marrow failure, and propensity to Thromboembolism
History and Epidemiology: first described in the 18th century. It is a rare disease, with a worldwide prevalence estimated in the range of 1-5 cases per million regardless of ethnicity; an increased prevalence is reported in some regions which also harbor higher incidence of aplastic anemia (eg, Thailand and some other Asian countries)
Unique feature: only hemolytic anemia caused by an acquired genetic defect
Pathophysiology:
Somatic mutation in the Phosphatidylinositol glycan complement group A gene(PIGA gene)
[Cause: PIGA is X-linked and subject to lyonization (random inactivation of one X chromosome in cells of females) leading to a single acquired mutation in the active PIGA gene of any given cell]
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Deficient specialized phospholipid called glycosylphosphatidylinositol (GPI) linked protein in a hematopoetic stem cell
PNH blood cells are deficient in three GPI-linked proteins that regulate complement activity:
(1) Decay-accelerating factor or CD55
(2) Membrane inhibitor of reactive lysis or CD59
28 июл 2024
