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

• Published in: International journal of hematology Vol. 102; no. 4; pp. 477 - 481
• Main Authors: Krabbe, Johannes G., Kemna, Evelien W. M., Strunk, Annuska L. M., Jobse, Pieter A., Kramer, P. A., Dikkeschei, L. D., van den Heuvel, L. P. W. J., Fijnheer, Rob, Verdonck, Leo F.
• Format: Journal Article
• Language: English
• Published: Tokyo Springer Japan 01.10.2015; Springer Nature B.V
• Subjects: ADAM Proteins - genetics; ADAMTS13 Protein; Age of Onset; Amino Acid Substitution; Case Report; Exons; Hematology; Heterozygote; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Mutation, Missense; Oncology; Purpura, Thrombotic Thrombocytopenic - genetics; Compound heterozygosity; Thrombotic thrombocytopenic purpura; ADAMTS13; Congenital
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-015-1849-2

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease, characterized by microangiopathic hemolytic anaemia and thrombocytopenia, resulting in neurologic and/or renal abnormalities. We report a 49-year-old patient with a history of thrombotic events, renal failure, and thrombocytopenia. Blood analysis demonstrated no ADAMTS13 activity in the absence of antibodies against ADAMTS13. The complete ADAMTS13 gene was sequenced, and two mutations were identified: one mutation on exon 24 (Arg1060Asp), which had previously been described, and a mutation on exon 27 (Met1260IlefsX34), which has not been reported. For these mutations, compound heterozygosity appears to be necessary to cause TTP, as family members of the patient display only one of the mutations and all displayed normal ADAMTS13 activity.