Pathogenesis

The PIG-A gene encodes an enzyme involved in the synthesis of glycosylphosphatidylinositol (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:	Not assigned (see Who's Who)
Last Reviewed:	November 2019
Next Review:	November 2022
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Note: Only the electronic version is controlled. Once printed, this is no longer a controlled document. Disclaimer The Haematology Department Protocols and Guidelines (the Red Book) are intended as a guide for registered health professionals to communicate guidelines and share best practices with supporting health professionals within New Zealand district health boards. They are not intended to be provided to or used as a reference for patients or non-registered health professionals. All health professionals must exercise their own clinical judgement and use pertinent clinical data when treating patients. The authors and editors of this publication have checked with sources believed to be reliable in their effort to provide information that is complete and in accord with the standards accepted at the time of publication. However, in view of the possibility of human error or changes in medical science, neither the authors, editors, publisher, nor any other party who has been involved in preparing or publishing this work warrants that the information contained in it is accurate or complete in every respect. They therefore have no liability (whether in tort (including negligence) or otherwise) for any loss or damage arising out of any reliance on this information. This publication has been compiled by the staff and contractors of Canterbury District Health Board (CDHB) and as such CDHB has copyright for this book. Amendments must be authorised in accordance with the documented process. No release of part of, or all of, this publication to any other party or organisation is permissible without the prior approval of the designated document owner.
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