Congenital thrombotic thrombocytopenic purpura with novel mutations in three unrelated turkish children

2013 ◽  
Vol 61 (3) ◽  
pp. 558-561 ◽  
Author(s):  
Ayse Metin ◽  
Sule Unal ◽  
Fatma Gümrük ◽  
Roberta Palla ◽  
Andrea Cairo ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Novel Mutations ◽  
Thrombocytopenic Purpura ◽  
Turkish Children ◽  
Congenital Thrombotic Thrombocytopenic Purpura

Congenital thrombotic thrombocytopenic purpura (cTTP) with two novel mutations

2012 ◽  
Vol 59 (7) ◽  
pp. 1296-1298 ◽  
Author(s):  
Timothy D. Prestidge ◽  
Erica Rurali ◽  
Louis Wadsworth ◽  
John K. Wu ◽  
Jane C. Moore ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Novel Mutations ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura

scholarly journals Characterization of Two Cases of Congenital Thrombotic Thrombocytopenic Purpura (TTP)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5005-5005
Author(s):  
Xia Bai ◽  
JIan Su ◽  
Lijuan Cao ◽  
Changgeng Ruan
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Binding Assay ◽  
Conflicts Of Interest ◽  
Hek293 Cells ◽  
Novel Mutations ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Introduction: Congenital thrombotic thrombocytopenic purpura (TTP) is characterized by disseminated thrombus due to the mutations of ADAMTS13, which cleaves its substrate von Willebrand factor(VWF) in shear-induced unfolding condition. Most of the congenital TTP we found is woman with pregnancy. Here, we characterize two children suspected with congenital TTP. Methods:ADAMTS13 activities were analyzed by residual collagen binding assay (R-CBA) plus FRET-VWF substrate. And the inhibitors of ADAMTS13 were analyzed by 9:1 mixture of patient and pooled normal plasma followed by R-CBA. The secretion of recombinant ADAMTS13 mutants was studied. Results: Two children, one aged four months and the other aged three years old, were diagnosed with congenital TTP because their ADAMTS13 activities were less than 5% (both FRET-VWF and R-CBA), and there are short of ADAMTS13 inhibitors. The following mutations were found: Q1385P, Y177C, C522R. In addition to the previously reported mutation of Y177C, the two novel mutations (Q1385P and C522R) failed to secrete from the HEK293 cells. Conclusion: Two children with congenital TTP were determined thanks to screening of ADAMTS13 activity and its corresponding inhibitor assays, and it seems that congenital TTP could occur in different ages although most of congenital TTP we found were women with pregnancy. Disclosures No relevant conflicts of interest to declare.

Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura

Blood ◽  
2004 ◽  
Vol 104 (7) ◽  
pp. 2081-2083 ◽  
Author(s):  
Toshihiro Uchida ◽  
Hideo Wada ◽  
Minoru Mizutani ◽  
Miho Iwashita ◽  
Hiroaki Ishihara ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Type I ◽  
Adamts13 Activity ◽  
Novel Mutations ◽  
Thrombocytopenic Purpura ◽  
Japanese Male ◽  
Old Japanese ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Von Willebrand

Abstract Congenital thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) is associated with an inherited von Willebrand factor-cleaving protease (ADAMTS13 [a disintegrin and metalloprotease with thrombospondin type I domains 13]) deficiency. In this study, we identified novel mutations in the ADAMTS13 gene in a patient with TTP. The patient was a 51-year-old Japanese male who exhibited TTP symptoms at frequent intervals. The ADAMTS13 activity during acute episodes was less than 3% that of normal. The enzyme activities of the patient's father and mother were both 46%, and both parents were asymptomatic. Genetic analysis revealed that the patient was a compound heterozygote for 2 mutations. One mutation was a missense mutation in the metalloprotease domain (A250V, exon 7), and the other was a guanine to adenine substitution at the 5′ end of intron 3 (intron 3 G→A). In vitro expression studies revealed that the A250V mutation markedly reduced ADAMTS13 activity and the intron 3 G→A mutation caused abnormal mRNA synthesis. (Blood. 2004;104: 2081-2083)

scholarly journals Characterization and treatment of congenital thrombotic thrombocytopenic purpura

Blood ◽  
2019 ◽  
Vol 133 (15) ◽  
pp. 1644-1651 ◽  
Author(s):  
Ferras Alwan ◽  
Chiara Vendramin ◽  
Ri Liesner ◽  
Amanda Clark ◽  
William Lester ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Age Of Onset ◽  
Organ Damage ◽  
Compound Heterozygous ◽  
Prophylactic Therapy ◽  
Thrombocytopenic Purpura ◽  
Stroke Incidence ◽  
End Organ Damage ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Diagnosis Age

Abstract Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years. Seventy-three cases of cTTP were diagnosed, confirmed by genetic analysis. Ninety-three percent were alive at the time of review. Thirty-six percent had homozygous mutations; 64% had compound heterozygous mutations. Two presentation peaks were seen: childhood (median diagnosis age, 3.5 years) and adulthood, typically related to pregnancy (median diagnosis age, 31 years). Genetic mutations differed by age of onset with prespacer mutations more likely to be associated with childhood onset (P = .0011). Sixty-nine percent of adult presentations were associated with pregnancy. Fresh-frozen plasma (FFP) and intermediate purity factor VIII concentrate were used as treatment. Eighty-eight percent of patients with normal blood counts, but with headaches, lethargy, or abdominal pain, reported symptom resolution with prophylactic therapy. The most common currently used regimen of 3-weekly FFP proved insufficient for 70% of patients and weekly or fortnightly infusions were required. Stroke incidence was significantly reduced in patients receiving prophylactic therapy (2% vs 17%; P = .04). Long-term, there is a risk of end-organ damage, seen in 75% of patients with late diagnosis of cTTP. In conclusion, prespacer mutations are associated with earlier development of cTTP symptoms. Prophylactic ADAMTS13 replacement decreases the risk of end-organ damage such as ischemic stroke and resolved previously unrecognized symptoms in patients with nonovert disease.

scholarly journals Pregnancy onset congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) mimicking HELLP syndrome: a case report

2021 ◽  
Vol 29 (3) ◽  
pp. 270-273
Author(s):  
Başak Ergin ◽  
Berna Buse Kobal ◽  
Zeynep Yazıcı ◽  
Ali Hakan Kaya ◽  
Sezin Canbek ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Hellp Syndrome ◽  
Epigastric Pain ◽  
Novel Mutation ◽  
Adamts13 Activity ◽  
Thrombotic Microangiopathies ◽  
Thrombocytopenic Purpura ◽  
Uremic Syndrome ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Low Platelet Count

Objective Thrombotic thrombocytopenic purpura is a thrombotic microangiopathic condition characterized by hemolytic anemia, thrombocytopenia, neurologic abnormalities, fever and renal dysfunction. Thrombotic microangiopathies such as preeclampsia and HELLP syndrome are pregnancy-specific, whereas others such as thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome are not. In this report, we present a case at which we identified a novel mutation which led to a significant reduction of ADAMTS13 activity. Case(s) A nulliparous pregnant woman of 32-year-old presenting with epigastric pain, hypertension and low platelet count was first suspected of HELLP syndrome, but was diagnosed with congenital TTP after delivery. Conclusion HELLP syndrome co-existed with undiagnosed TTP in this case. We strive to have sufficient awareness in order to distinguish these two pathologies from each other on an antenatal basis, because the causes of the managements are entirely different.

scholarly journals Multiplein silicotools predict phenotypic manifestations in congenital thrombotic thrombocytopenic purpura

2013 ◽  
Vol 160 (6) ◽  
pp. 825-837 ◽  
Author(s):  
Zachary A. Hing ◽  
Tal Schiller ◽  
Andrew Wu ◽  
Nobuko Hamasaki-Katagiri ◽  
Evi Budo Struble ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura
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