Haemoglobinuria paroxysmal nocturnal59.5

Rare (incidence of 1:100,000-1:500,000) genetic disease characterized by hemolytic anemia, thrombophilia and pancytopenia.

In paroxysmal nocturnal hemoglobinuria, a mutation of the gene for phosphatidyl-isonitol-glycan-A (PIGA) was detected. The phosphatidyl-isonitol-glycan-A gene, PIGA gene for short, codes for the enzyme N-acetyl-glucosaminyl-transferase. This enzyme anchors the acetylated glucosamine residue of the membrane protection protein GPI to the cell membrane receptor. This protective function protects the cell from the body's own complement system. Other protective proteins (e.g. CD55 and CD59 see CD classification) also bind to this membrane protective protein. CD55 and CD59 are also protective factors against the body's own complement system.

Due to the defect of the N-acetyl-glucosaminyl-transferase, the protective surface proteins can no longer attach themselves to the cell membrane of multipotent stem cells. The cell membrane is lysed intravascularly due to the missing protective function. The consequence is thrombocytopenia and thrombophilia. Dermatologically, this disease is of importance due to its combined occurrence with Pyoderma gangraenosum.

1. Goulden V et al (1994) Pyoderma gangrenosum associated with paroxysmal nocturnal haemoglobinuria. Clin Exp Dermatol 19:271-273
2. Matsubara K et al (2002) Pyoderma gangrenosum associated with paroxysmal nocturnal hemoglobulinuria and monoclonal gammopathy. J Dermatol 29:86-90
3. White JM et al(2003) Haemorrhagic bullae in a case of paroxysmal nocturnal haemoglobinuria. Clin Exp Dermatol 28:504-505