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Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria

Robert A Brodsky, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Alan G Rosmarin, MD


Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disorder with an unusual constellation of clinical findings. The rarity of the disease and nonspecific clinical features can result in significant delays in diagnosis. The importance of a prompt and accurate diagnosis has increased as effective therapies have become available, and diagnostic testing has evolved significantly as the molecular basis of the disease and pathogenesis of hemolysis become better understood.

This topic review will discuss the clinical manifestations and diagnosis of PNH. Detailed discussions of PNH pathogenesis, management, and prognosis are presented separately. (See "Pathogenesis of paroxysmal nocturnal hemoglobinuria" and "Treatment and prognosis of paroxysmal nocturnal hemoglobinuria".)


PNH is a rare disorder. Reported incidence of clinically significant disease is in the range of 1 to 10 cases per million population, although this may be an underestimate as a subset of patients are likely to remain undiagnosed [1,2].

PNH is mostly a disease of adults, although childhood cases have been reported [3-5]. The median age of onset is in the thirties [6,7].

PNH affects males and females nearly equally despite being caused by mutation of a gene on the X chromosome. This is because PNH results from an acquired mutation in a somatic rather than a germline cell, and somatic cells, including hematopoietic stem cells, only use one X chromosome [8]. (See "Pathogenesis of paroxysmal nocturnal hemoglobinuria", section on 'PIGA gene mutation'.)

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Literature review current through: Nov 2017. | This topic last updated: Nov 13, 2017.
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