Long term follow up of congenital thrombotic thrombocytopenic purpura (Upshaw-Schulman syndrome) on hemodialysis for 19 years: a case report

BMC Nephrology

Kenmei Takaichi¹  Yoshihiro Fujimura⁴  Toshiyuki Miyata³  Koichi Kokame³  Kenichi Ohashi²  Naoki Sawa⁵  Junichi Hoshino⁶  Tatsuya Suwabe⁶  Noriko Hayami⁶  Masayuki Yamanouchi⁵  Eiko Hasegawa⁵  Rikako Hiramatsu⁵  Keiichi Sumida⁶  Masanori Matsumoto⁴  Yoshifumi Ubara⁶  Koki Mise⁶ 

[1] Okinaka Memorial Institute for Medical Research, Toranomon Hospital, Tokyo, Japan;Department of Pathology, Toranomon Hospital, Tokyo, Japan;Department of Molecular Pathogenesis, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan;Department of Blood Transfusion Medicine, Nara Medical University, Nara, Japan;Nephrology Center, Toranomon Hospital, Tokyo, Japan;Nephrology Center, Toranomon Hospital Kajigaya, 1-3-1, Kajigaya, Takatu-ku, Kawasaki-shi, Kanagawa-ken 213-0015, Japan

关键词: Alternative pathway;    C3;    Complement activation;    Chronic hemodialysis;    ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I domain 13);    Congenital thrombotic thrombocytopenic purpura;   

Others  :  1082883
DOI  :  10.1186/1471-2369-14-156

 received in 2013-03-08, accepted in 2013-07-09,  发布年份 2013

【 摘 要 】

Background

Thrombotic thrombocytopenic purpura (TTP) is frequently associated with renal abnormalities, but there have been few reports about renal abnormalities in patients with hereditary TTP. In particular, little is known about the long-term prognosis of patients with childhood-onset congenital TTP.

Case presentation

We report a Japanese patient with congenital TTP (Upshaw–Schulman syndrome) who was followed for 19 years after initiation of hemodialysis when he was 22 years old. At the age of 6 years, the first episode of purpura, thrombocytopenia, and proteinuria occurred without any precipitating cause. He underwent living-related donor kidney transplantation from his mother, but the graft failed after 5 months due to recurrence of TTP. Even after resection of the transplanted kidney and resumption of regular hemodialysis, TTP became refractory to infusion of fresh frozen plasma (FFP). Therefore, splenectomy was performed and his disease remained in remission for 10 years. However, TTP recurred at the age of 39 years. Plasma activity of ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type I domain 13) was less than 3%, while ADAMTS13 inhibitor was not detected (< 0.5 Bethesda units/mL). The patient died suddenly after hemodialysis at the age of 41 years. Subsequent genetic analysis of this patient and his parents revealed two different heterozygous mutations of ADAMTS13, including a missense mutation in exon 26 (c.3650T>C causing p.I1217T) inherited from his father and a missense mutation in exon 21 (c.2723G>A causing p.C908Y) inherited from his mother. The former mutation has not been detected before in Japan, while the latter mutation is common in Japan. A retrospective review showed that serum C3 levels were consistently low while C4 levels were normal during follow-up, and C3 decreased much further during each episode of TTP.

Conclusion

Congenital TTP was diagnosed from the clinical, biochemical, and genetic findings. Infusion of FFP controlled each thrombotic episode, but the effect was limited and of short duration. Review of the complement profile in this patient suggested that a persistently low serum C3 level might be associated with refractory TTP and a worse renal prognosis.

【 授权许可】

   
2013 Mise et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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