Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS)

Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are now considered to be variants of one single syndrome called thrombotic thrombocytopenic purpura/hemolytic-ur...

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Bibliographic Details
Published in:Kidney international 2004-09, Vol.66 (3), p.955-958
Main Authors: Licht, Christoph, Stapenhorst, Ludwig, Simon, Thorsten, Budde, Ulrich, Schneppenheim, Reinhard, Hoppe, Bernd
Format: Article
Language:English
Subjects:
ADAM Proteins
ADAMTS13 gene mutation
ADAMTS13 Protein
Anemias. Hemoglobinopathies
Biological and medical sciences
Child
Diseases of red blood cells
Hematologic and hematopoietic diseases
hemolytic uremic syndrome (HUS)
Hemolytic-Uremic Syndrome - blood
Hemolytic-Uremic Syndrome - genetics
Humans
Male
Medical sciences
Metalloendopeptidases - blood
Metalloendopeptidases - genetics
Nephrology. Urinary tract diseases
Nephropathies. Renovascular diseases. Renal failure
Pedigree
Platelet diseases and coagulopathies
Point Mutation
Purpura, Thrombotic Thrombocytopenic - blood
Purpura, Thrombotic Thrombocytopenic - genetics
Renal failure
thrombotic thrombocytopenic purpura (TTP)
von Willebrand factor-cleaving protease (vWF-CP)
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Summary:Two novel ADAMTS13 gene mutations in thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) are now considered to be variants of one single syndrome called thrombotic thrombocytopenic purpura/hemolytic-uremic syndrome (TTP/HUS). Key features are thrombocytopenia, hemolytic anemia, and subsequently impaired function of different organs, especially the kidneys and the central nervous system (CNS). One possible reason is the deficiency of von Willebrand factor-cleaving protease (vWF-CP) resulting in persistence of uncleaved, ultralarge von Willebrand factor multimers (ULvWFM). We report a patient who was initially diagnosed with Evans syndrome (hemolytic anemia and autoimmune thrombocytopenia) as infant. At 10 years of age he developed HUS-like disease with gastrointestinal tract infection, hemolytic anemia, thrombocytopenia,and acute renal failure. However, enteropathogenic Escherichia coli–like or Shiga-like toxins were not detected. Further investigations revealed severe deficiency (40%) of vWF-CP activity caused by compound heterozygosity of two novel ADAMTS13 gene mutations (1170 G>C [W390C] and 3735 G>A [W1245X]. vWF-CP autoantibodies were not detected. Periodic (every 2 weeks) treatment with fresh frozen plasma (FFP) maintained both platelet level and kidney function within normal range and prevented new episodes of TTP/HUS. Enteropathogenic E. coli– and Shiga-like toxin-negative patients who present with hemolytic or thrombocytopenic episodes and HUS like symptoms should be tested for vWF-CP deficiency and other noninfectious reasons for TTP/HUS since plasma substitution possibly provides an efficient therapeutic option for this subgroup of patients.
ISSN:0085-2538
1523-1755
DOI:10.1111/j.1523-1755.2004.00841.x