Paroxysmal Nocturnal Hemoglobinuria (PNH)
Description
Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare, chronic blood disorder that affects red blood cells, leading to their premature destruction. This destruction can cause anemia, fatigue, and other serious complications. While there is no cure for PNH, treatments are available to manage symptoms and improve quality of life.
Genes Involved
PNH is caused by a mutation in the PIGA gene. This gene provides instructions for making an enzyme called phosphatidylinositol glycan class A, which is involved in the synthesis of a molecule called glycosylphosphatidylinositol (GPI). GPI anchors are essential for attaching proteins to the surface of red blood cells. Mutations in the PIGA gene lead to a deficiency in GPI, making red blood cells susceptible to destruction by the immune system.
Recognizing the Signs and Symptoms
The symptoms of PNH can vary widely depending on the severity of the disease. Some common signs and symptoms include:
- Fatigue and weakness: PNH can cause anemia, which leads to a decrease in the oxygen-carrying capacity of the blood, resulting in fatigue and weakness.
- Dark urine: Hemoglobin released from destroyed red blood cells can color the urine dark, sometimes described as "port-wine" colored.
- Pain in the abdomen: The destruction of red blood cells can cause pain in the abdomen.
- Blood clots: PNH can increase the risk of blood clots, particularly in the veins of the legs (deep vein thrombosis) or lungs (pulmonary embolism).
- Yellowing of the skin and eyes (jaundice): Jaundice can occur when the body is unable to break down bilirubin, a byproduct of red blood cell breakdown.
- Frequent infections: PNH can weaken the immune system, making individuals more susceptible to infections.
- Pain in the bones: Bone pain may occur due to the increased production of red blood cells in the bone marrow.
- Swelling in the legs and ankles: Swelling can occur due to fluid buildup in the tissues.
Causes
PNH is caused by a mutation in the PIGA gene. This mutation is typically acquired, meaning it is not inherited from parents. The exact cause of the mutation is unknown, but it is thought to be caused by a combination of genetic and environmental factors. In rare cases, PNH can be inherited, but this is uncommon.
Inheritance/recurrence risk
PNH is typically not inherited from parents, making recurrence risk in future generations very low. However, in extremely rare cases, PNH can be inherited, usually from a parent with a very rare genetic condition called PIGA deficiency. In these cases, the risk of inheritance is 50%.
