Paroxysmal nocturnal hemoglobinuria.

Abstract:

:Paroxysmal nocturnal hemoglobinuria (PNH) is a rare bone marrow failure disorder that manifests with hemolytic anemia, thrombosis, and peripheral blood cytopenias. The absence of two glycosylphosphatidylinositol (GPI)-anchored proteins, CD55 and CD59, leads to uncontrolled complement activation that accounts for hemolysis and other PNH manifestations. GPI anchor protein deficiency is almost always due to somatic mutations in phosphatidylinositol glycan class A (PIGA), a gene involved in the first step of GPI anchor biosynthesis; however, alternative mutations that cause PNH have recently been discovered. In addition, hypomorphic germ-line PIGA mutations that do not cause PNH have been shown to be responsible for a condition known as multiple congenital anomalies-hypotonia-seizures syndrome 2. Eculizumab, a first-in-class monoclonal antibody that inhibits terminal complement, is the treatment of choice for patients with severe manifestations of PNH. Bone marrow transplantation remains the only cure for PNH but should be reserved for patients with suboptimal response to eculizumab.

journal_name

Blood

journal_title

Blood

authors

Brodsky RA

doi

10.1182/blood-2014-02-522128

subject

Has Abstract

pub_date

2014-10-30 00:00:00

pages

2804-11

issue

18

eissn

0006-4971

issn

1528-0020

pii

blood-2014-02-522128

journal_volume

124

pub_type

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