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DOI: 10.1055/s-0040-1721573
The International Hereditary Thrombotic Thrombocytopenic Purpura Registry: Key findings at Enrolment until 2017
Congenital thrombotic thrombocytopenic purpura is an autosomal recessive inherited disease with a clinically heterogeneous course and an incompletely understood genotype–phenotype correlation. In 2006, the Hereditary TTP Registry started recruitment with the purpose of improving the understanding of this ultra-rare disease. The objective of this study is to present characteristics of the cohort until the end of 2017 and to explore the relationship between overt disease onset and ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity with emphasis on the recurring ADAMTS-13 c.4143_4144dupA mutation. Diagnosis of congenital thrombotic thrombocytopenic purpura was confirmed by severely deficient ADAMTS-13 activity (<10% of normal) in the absence of a functional inhibitor and the presence of ADAMTS-13 mutations on both alleles. By the end of 2017, a total of 123 confirmed patients were enrolled from Europe (55), Asia (52, 90% from Japan), America (14), and Africa (2). First recognized disease manifestation occurred around birth up to the age of 70 years. Of the 97 different ADAMTS-13 mutations detected, c.4143_4144dupA (exon 29; p.Glu1382Argfs*6) was the most frequent mutation, present on 60 of 246 alleles. We found a larger proportion of compound heterozygous than homozygous carriers of ADAMTS-13 c.4143_4144dupA with overt disease onset at <3 months of age (50 vs. 37%), despite the fact that ADAMTS-13 activity was <1% in 18 of 20 homozygous carriers, but in only 8 of 14 compound heterozygous carriers. Evaluating overt disease onset in all patients with a sensitive ADAMTS-13 activity determination available (n = 97), it becomes evident that residual ADAMTS-13 activity is not the only determinant of the age at first disease manifestation (clinicaltrials.gov identifier NCT01257269).
Haematologica 2019 Feb 21. pii: haematol.2019.216796. doi: 10.3324/haematol.2019.216796. [Epub ahead of print]
Publication History
Article published online:
13 November 2020
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