Thrombomodulin Mutations in Atypical Hemolytic–Uremic Syndrome

Atypical hemolytic–uremic syndrome, a complex of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, is not associated with shigella toxin — unlike typical hemolytic–uremic syndrome — but is often associated with abnormal activation of complement by mutant components of the syste...

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Published in:The New England journal of medicine Vol. 361; no. 4; pp. 345 - 357
Main Authors: Delvaeye, Mieke, Noris, Marina, De Vriese, Astrid, Esmon, Charles T, Esmon, Naomi L, Ferrell, Gary, Del-Favero, Jurgen, Plaisance, Stephane, Claes, Bart, Lambrechts, Diether, Zoja, Carla, Remuzzi, Giuseppe, Conway, Edward M
Format: Journal Article
Language:English
Published: Waltham, MA Massachusetts Medical Society 23.07.2009
Subjects:
Adolescent
Adult
Biological and medical sciences
Child
Complement Activation - genetics
Complement C3b
Complement Factor I
Complement Pathway, Alternative - physiology
DNA Mutational Analysis
Excretory system
General aspects
Genomics
Hematologic and hematopoietic diseases
Hemolytic-Uremic Syndrome - genetics
Hemolytic-Uremic Syndrome - immunology
Heterozygote
Humans
Medical disorders
Medical sciences
Middle Aged
Mutation, Missense
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Pedigree
Platelet diseases and coagulopathies
Polymorphism, Single Nucleotide
Proteins
Renal failure
Thrombomodulin - genetics
Thrombomodulin - metabolism
Young Adult
Kidney disease
Thrombocytopenia
Urinary system disease
Hemolytic uremic syndrome
Acute
Cardiovascular disease
Hemopathy
Thrombohemolytic microangiopathy
Vascular disease
Medicine
Platelet
Hemolytic anemia
Renal failure
Genetics
Atypical
Mutation
Thrombomodulin
ISSN:0028-4793, 1533-4406, 1533-4406
Online Access:Get full text
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Summary:Atypical hemolytic–uremic syndrome, a complex of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure, is not associated with shigella toxin — unlike typical hemolytic–uremic syndrome — but is often associated with abnormal activation of complement by mutant components of the system. This study shows that in some patients with the atypical syndrome, there are disabling mutations of the THBD gene, which encodes thrombomodulin. As a result of these mutations, regulation of complement activation on cell surfaces is impaired, and cells are not protected from activated complement. This study shows that in some patients with the atypical hemolytic–uremic syndrome, there are disabling mutations of the THBD gene, which encodes thrombomodulin. As a result of these mutations, regulation of complement activation on cell surfaces is impaired, and cells are not protected from activated complement. The hemolytic–uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. It is one of the thrombotic microangiopathies, along with thrombotic thrombocytopenia purpura and preeclampsia. 1 The hemolytic–uremic syndrome is the most common cause of acute renal failure among children, a condition for which 50 to 75% of patients require dialysis. 2 More than 85% of cases of the hemolytic–uremic syndrome are referred to as “typical”; these are preceded by diarrhea caused by strains of Escherichia coli 3 – 5 that produce Shiga-like toxins, which have proinflammatory and prothrombotic effects on the vascular endothelium. 6 Most cases of typical hemolytic–uremic . . .
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ISSN:0028-4793
1533-4406
1533-4406
DOI:10.1056/NEJMoa0810739