Genotypic, immunophenotypic and clinical features of Thai patients with paroxysmal nocturnal haemoglobinuria

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired haematological di sorder characterized by complement-mediated haemolytic anaemia caused by de ficiency of glycosylphosphatidylinositol (GPI) anchored proteins. Somatic m utation of an X-linked gene, PIG-A, is responsible for the defect in biosyn thesis of GPI-anchor. It appears that frequency of PNH differs geographical ly, and seems to be more frequent in some Asian countries, such as Thailand and China. We studied a group of 34 Thai patients with PNH to see whether the somatic mutations in PIG-A, extent of deficiency of GPI-anchored protei ns (complete or partial) and complication with aplastic anaemia among Thai patients are different from those in other regions. We determined 37 PIG-A mutations in 33 patients (10 base substitutions, 14 single-base deletions, five multiple-base deletions, three single-base insertions, two multiple ba se insertions and three others) which were found to be similar to those fou nd in European, American and Japanese patients. Most patients had cells wit h a complete deficiency of CD59 (type III cells), whereas 19% and 33% of th e patients with reliable data for CD59 expression had partially deficient g ranulocytes and erythrocytes (type II cells), respectively Most mutations r esulted in a complete loss of function of PIG-A in accordance with the prev alent PNH Ln phenotype. 19 patients (51%) had aplastic anaemia; their PIG-A mutations were not different from those without pre-existing aplastic anae mia. These characteristics of Thai patients are similar to patients from ot her regions. There was some negative correlation between mean basal Hb conc entration and percentage of CD59-negative granulocytes (r = -0.374: P = 0.0 476). In addition, patients with severe anaemia (basal Hb <7 g/dl) had a si gnificantly higher percentage of affected granulocytes than those with mild anaemia (88.5 +/- 9.4 v 64.9 +/- 25.9; P = 0.01). The data suggest that th e severity of anaemia in PNH depends partly on the size of the PNH clone.