Adult-onset congenital thrombotic thrombocytopenic purpura caused by a novel compound heterozygous mutation of the ADAMTS13 gene

2015 ◽  
Vol 102 (4) ◽  
pp. 477-481 ◽  
Author(s):  
Johannes G. Krabbe ◽  
Evelien W. M. Kemna ◽  
Annuska L. M. Strunk ◽  
Pieter A. Jobse ◽  
P. A. Kramer ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Adult Onset ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura

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.

Congenital thrombotic thrombocytopenic purpura caused by new compound heterozygous mutations of theADAMTS13gene

2013 ◽  
Vol 92 (2) ◽  
pp. 168-171 ◽  
Author(s):  
Cecilie Utke Rank ◽  
Johanna Kremer Hovinga ◽  
Magnus Mansouri Taleghani ◽  
Bernhard Lämmle ◽  
Jens Peter Gøtze ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Compound Heterozygous ◽  
Thrombocytopenic Purpura ◽  
Congenital Thrombotic Thrombocytopenic Purpura ◽  
Compound Heterozygous Mutations

A new compound heterozygous mutation in adult-onset Krabbe disease

2020 ◽  
Vol 130 (12) ◽  
pp. 1267-1271 ◽  
Author(s):  
Xianghe Meng ◽  
Yingjiao Li ◽  
Yajun Lian ◽  
Yujuan Li ◽  
Liyuan Du ◽  
...  
Keyword(s):  
Krabbe Disease ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Adult Onset
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