Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disease that presents clinically with a variety of symptoms, the most prevalent of which are hemolytic anemia, hemoglobinuria, and somatic symptoms including fatigue and shortness of breath. Other findings associated with PNH include thrombosis, renal insufficiency, and in the later course of the disease, even bone marrow failure. The condition is genetic, with the mutations occurring on the X linked gene.
While the term paroxysmal nocturnal hemoglobinuria was introduced by Enneking in 1925, case reports dating back to the 1880s can be found. One of the earliest was that of Strubing, who documented the case of a young adult man with fatigue, abdominal pain, and intermittent hemoglobinuria. Strubing also noted that the patient's plasma was red following the most severe episodes, and he deduced that intravascular hemolysis was the cause. Later in 1937, Ham was able to discover that erythrocytes of individuals with PNH hemolyzed when incubated with normal acidified urine. This resulted in the first diagnostic test for PNH, known as the Ham test (acidified serum test). While complement activation was suspected as the etiology for hemolysis, the theory was not formally proven until 1954. Over the following years, the nature of protein deficiencies affecting PNH erythrocytes was identified, and this paved the way for the identification of the responsible genetic mutation.
Although PNH is a rare condition, it has a significant impact on the quality of life of a patient. About 4 or 5 decades ago 10-year survival for this condition was only 50 percent. However, in the last 15 years, advances in treatment such as the development of eculizumab have improved survival to more than 75 percent.