Canterbury DHB

Context

Pathogenesis

The PIG-A gene encodes an enzyme involved in the synthesis of glucosylphosphatidylinositol (GPI). Cells derived from the PNH clone lack GPI on their surface. Therefore, any proteins attached to the cell surface via the GPI link will not be present.

In PNH, haemolysis is caused by a loss of the decay accelerating factor (DAF, CD55). There is also loss of membrane inhibitor of reactive lysis (MIRL, CD59), which regulates complement activation. Both DAF and MIRL are normally present on the red cell surface. The variable expression of the PIG-A gene defect accounts for the wide range of clinical severity seen. A patient may have differing percentages of normal, mildly affected, or severely affected red cells with the PNH defect and a variable spread into other haematopoietic cells. The severity of the defect may also vary with time. PNH is therefore an acquired stem cell disorder caused by mutation of the PIG-A gene, located on the short arm of the X-chromosome.

About this Canterbury DHB document (4936):

Document Owner:

Mark Smith (see Who's Who)

Issue Date:

August 2017

Next Review:

August 2019

Keywords:

Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer

Topic Code: 4936