Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan

Y. Fujimura, M. Matsumoto, A. Isonishi, H. Yagi, K. Kokame, K. Soejima, Mitsuru Murata, T. Miyata

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Abstract

Upshaw-Schulman syndrome (USS) is an extremely rare hereditary deficiency of ADAMTS13 activity, termed congenital TTP. The clinical signs are usually mild during childhood, often with isolated thrombocytopenia. But their symptoms become more evident when patients have infections or get pregnant. We identified 43 USS-patients in Japan, who ranged in age from early childhood to 79years of age. Analysing the natural history of these USS patients based on ADAMTS13 gene mutations may help characterise their clinical phenotypes. Severe neonatal jaundice that requires exchange blood transfusion, a hallmark of USS, was found in 18 of 43 patients (42%). During childhood, 25 of 43 patients were correctly diagnosed with USS without gender disparity. These 25 patients were categorised as having 'the early-onset phenotype'. Between 15 and 45years of age, 15 were correctly diagnosed, and, interestingly, they were all female. The remaining three patients were male and were diagnosed when they were older than 45years of age, suggesting that they were 'the late-onset phenotype'. Two of these three males developed sudden overt TTP when they were 55 and 63years old, respectively. These two men had two different homozygous ADAMTS13 gene mutations, p.R193W/p.R193W and p.C1024R/p.C1024R, respectively. Both of which were not discovered in the US or Western countries. In vitro expression studies showed that these two proteins were consistently secreted into the culture medium but to a lesser extent and with reduced activity compared to the wild-type protein. Our results indicate that 'the late-onset phenotype' of USS is formed with ethnic specificity.

Original languageEnglish
Pages (from-to)283-301
Number of pages19
JournalJournal of Thrombosis and Haemostasis
Volume9
Issue number1 S
DOIs
Publication statusPublished - 2011 Jul

Fingerprint

Thrombotic Thrombocytopenic Purpura
Japan
Genes
Phenotype
Neonatal Jaundice
Mutation
Blood Transfusion
Thrombocytopenia
Culture Media
Proteins
Infection

Keywords

  • ADAMTS13 gene mutation
  • Clinical phenotype
  • Natural history
  • Upshaw-Schulman syndrome

ASJC Scopus subject areas

  • Hematology

Cite this

Fujimura, Y., Matsumoto, M., Isonishi, A., Yagi, H., Kokame, K., Soejima, K., ... Miyata, T. (2011). Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. Journal of Thrombosis and Haemostasis, 9(1 S), 283-301. https://doi.org/10.1111/j.1538-7836.2011.04341.x

Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. / Fujimura, Y.; Matsumoto, M.; Isonishi, A.; Yagi, H.; Kokame, K.; Soejima, K.; Murata, Mitsuru; Miyata, T.

In: Journal of Thrombosis and Haemostasis, Vol. 9, No. 1 S, 07.2011, p. 283-301.

Research output: Contribution to journalArticle

Fujimura, Y, Matsumoto, M, Isonishi, A, Yagi, H, Kokame, K, Soejima, K, Murata, M & Miyata, T 2011, 'Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan', Journal of Thrombosis and Haemostasis, vol. 9, no. 1 S, pp. 283-301. https://doi.org/10.1111/j.1538-7836.2011.04341.x
Fujimura, Y. ; Matsumoto, M. ; Isonishi, A. ; Yagi, H. ; Kokame, K. ; Soejima, K. ; Murata, Mitsuru ; Miyata, T. / Natural history of Upshaw-Schulman syndrome based on ADAMTS13 gene analysis in Japan. In: Journal of Thrombosis and Haemostasis. 2011 ; Vol. 9, No. 1 S. pp. 283-301.
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