title: Novel compound heterozygote mutations (H234Q/R1206X) of the ADAMTS13 gene in an adult patient with Upshaw-Schulman syndrome showing predominant episodes of repeated acute renal failure.
abstract: BACKGROUND
  Unlike acquired thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome, which are often intractable, thrombotic microangiopathy in patients with Upshaw-Schulman syndrome (USS)--a congenital deficiency of von Willebrand factor-cleaving protease (ADAMTS13) activity--responds very well to plasma infusion and does not even require plasma exchange. However, the symptoms significantly vary in each individual and thus clinicians often overlook this diagnosis.
  
  
  METHODS
  A 31-year-old adult male patient with thrombotic microangiopathy, which was complicated with repeated episodes of acute renal failure, is reported. We suspected that the patient had USS and performed assays of ADAMT13 activity and its inhibitor, followed by ADAMTS13 gene analysis of the patient and his parents.
  
  
  RESULTS
  The patient had extremely low ADAMTS13 activity and has no inhibitors of ADAMTS13. Through an ADAMTS13 gene analysis of this family, we found two novel mutations responsible for the disease: a missense mutation in exon 7 [702 C --> A (H234Q)] from the father and a nonsense mutation in exon 26 [3616 C --> T (R1206X)] from the mother.
  
  
  CONCLUSIONS
  Our experience appears to indicate the importance of assays of ADAMTS13 activity and its inhibitor in patients who have episodes of renal insufficiency in association with thrombotic microangiopathy, for diagnosis and choice of treatment.
authors.affiliation: Department of Nephrology and Endocrinology, Graduate School of Medicine, University of Tokyo, Japan. eugo@wc4.so-net.ne.jp
authors.forename: Yugo
authors.initials: Y
authors.lastname: Shibagaki
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Kokame
authors.forename: Shigeyoshi
authors.initials: S
authors.lastname: Ohba
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miyata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.forename: Toshiro
authors.initials: T
authors.lastname: Fujita
mesh_terms: D051722:ADAM Proteins / Q000235:genetics*; D000071120:ADAMTS13 Protein; D058186:Acute Kidney Injury / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D000328:Adult; D018450:Disease Progression; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D012008:Recurrence
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human