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.
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Shibagaki Y, Matsumoto M, Kokame K, Ohba S, Miyata T, Fujimura Y, Fujita T
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.
Nephrol Dial Transplant. 2006 May;21(5):1289-92. doi: 10.1093/ndt/gfk072. Epub 2006 Jan 31.
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- 16449289 [ View in PubMed]
- 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.