Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy disorder associated with congenital or acquired deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The central nervous system and kidneys are the two major organs of involvement in TTP. Moyamoya (puff of smoke) disease is a cerebral arteriopathy of unknown etiology characterized by narrowing or occlusion of the distal internal carotid or proximal anterior or middle cerebral arteries, which causes the formation of multiple tiny collateral networks. We report here a case of an 11-year-old boy with unilateral moyamoya disease and congenital TTP. The patient had a history of severe neonatal jaundice and thereafter recurrent episodes of hemolytic anemia associated with renal dysfunction and cerebral infarction. The plasma ADAMTS13 activity of the patient <3% of normal, and ADAMTS13 gene analysis revealed an abnormal splicing mutation (c.330+1 G > A) in one allele and a novel missense mutation (p.Ile1217Thr) in the other. This is the first case of a genetically confirmed congenital TTP associated with unilateral moyamoya disease. Although the causal relationship between the two diseases has not been established, TTP may be included as one of the causes of moyamoya syndrome.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
Tax calculation will be finalised during checkout.
Levy GG, Nichols WC, Lian EC, Foroud T, McClintick JN, McGee BM, Yang AY, Siemieniak DR, Stark KR, Gruppo R, Sarode R, Shurin SB, Chandrasekaran V, Stabler SP, Sabio H, Bouhassira EE, Upshaw JD Jr, Ginsburg D, Tsai HM (2001) Mutations in a member of the ADAMTS gene family cause thrombotic thrombocytopenic purpura. Nature 413:488–494
Kokame K, Matsumoto M, Soejima K, Yagi H, Ishizashi H, Funato M, Tamai H, Konno M, Kamide K, Kawano Y, Miyata T, Fujimura Y (2002) Mutations and common polymorphisms in ADAMTS13 gene responsible for von Willebrand factor-cleaving protease activity. Proc Natl Acad Sci USA 99:11902–11907
Furlan M, Robles R, Solenthaler M, Lammle B (1998) Acquired deficiency of von Willebrand factor-cleaving protease in a patient with thrombotic thrombocytopenic purpura. Blood 91:839–2846
Tsai HM, Lian EC (1998) Antibodies to von Willebrand factor-cleaving protease in acute thrombotic thrombocytopenic purpura. N Engl J Med 339:1585–1594
Hoffman HJ (1997) Moyamoya disease and syndrome. Clin Neurol Neurosurg 99(Suppl 2):S39–S44
Gosalakkal JA (2002) Moyamoya disease: a review. Neurol India 50:6–10
Hiyama H, Kusano R, Muragaki Y, Miura N (1994) Moyamoya disease associated with thrombotic thrombocytopenic purpura (TTP). No Shinkei Geka 22:567–572
Furlan M, Robles R, Morselli B, Sandoz P, Lämmle B (1999) Recovery and half-life of von Willebrand factor-cleaving protease after plasma therapy in patients with thrombotic thrombocytopenic purpura. Thromb Haemost 81:8–13
Kinoshita S, Yoshioka A, Park YD, Ishizashi H, Konno M, Funato M, Matsui T, Titani K, Yagi H, Matsumoto M, Fujimura Y (2001) Upshaw-Schulman syndrome revisited: a concept of congenital thrombotic thrombocytopenic purpura. Int J Hematol 74:101–108
Matsumoto M, Kokame K, Soejima K, Miura M, Hayashi S, Fujii Y, Iwai A, Ito E, Tsuji Y, Takeda-Shitaka M, Iwadate M, Umeyama H, Yagi H, Ishizashi H, Banno F, Nakagaki T, Miyata T, Fujimura Y (2004) Molecular characterization of ADAMTS13 gene mutations in Japanese patients with Upshaw-Schulman syndrome. Blood 103:1305–1310
Uchida T, Wada H, Mizutani M, Iwashita M, Ishihara H, Shibano T, Suzuki M, Matsubara Y, Soejima K, Matsumoto M, Fujimura Y, Ikeda Y, Murata M, Research Project on Genetics of Thrombosis (2004) Identification of novel mutations in ADAMTS13 in an adult patient with congenital thrombotic thrombocytopenic purpura. Blood 104:2081–2083
Bork P, Beckmann G (1993) The CUB domain. A widespread module in developmentally regulated proteins. J Mol Biol 231:539–545
Pimanda JE, Maekawa A, Wind T, Paxton J, Chesterman CN, Hogg PJ (2004) Congenital thrombotic thrombocytopenic purpura in association with a mutation in the second CUB domain of ADAMTS13. Blood 103:627–629
Shang D, Zheng XW, Niiya M, Zheng XL (2006) Apical sorting of ADAMTS13 in vascular endothelial cells and Madin-Darby canine kidney cells depends on the CUB domains and their association with lipid rafts. Blood 108:2207–2215
Zhang P, Pan W, Rux AH, Sachais BS, Zheng XL (2007) The cooperative activity between the carboxyl-terminal TSP1 repeats and the CUB domains of ADAMTS13 is crucial for recognition of von Willebrand factor under flow. Blood 110:1887–1894
Fukui M, Members of the Research Committee on spontaneous Occlusion of the Circle of Willis (Moyamoya disease) of Ministry and Welfare, Japan (1997) Guidelines for the diagnosis and treatment of spontaneous occlusion of the circle of Willis (Moyamoya’ disease) of the Ministry of Healthand Welfare, Japan. Clin Neurol Neurosurg 99:S238–S240
Houkin K, Abe H, Yoshimoto T, Takahashi A (1996) Is unilateral Moyamoya disease different from moyamoya disease. J Neurosurg 85:772–776
Ikezaki K, Han DH, Kawano T, Kinukawa N, Fukui M (1997) A clinical comparison of definite moyamoya disease between South Korea and Japan. Stroke 28:2513–2517
This study was partially supported by a grant from the Korean Society of Pediatric Nephrology (2004 Ferring Research Grant).
About this article
Cite this article
Park, H.W., Oh, D., Kim, N. et al. Congenital thrombotic thrombocytopenic purpura associated with unilateral moyamoya disease. Pediatr Nephrol 23, 1555–1558 (2008). https://doi.org/10.1007/s00467-008-0847-5
- Congenital thrombotic thrombocytopenic purpura
- Moyamoya disease
- ADAMTS13 gene
- Von Willebrand factor-cleaving protease