High prevalence of hereditary thrombotic thrombocytopenic purpura in Central Norway: from clinical observation to evidence.

Background: Hereditary thrombotic thrombocytopenic purpura (TTP) caused by ADAMTS-13 mutations is a rare, but serious condition. The prevalence is unknown, but it seems to be high in Norway. Objectives: To identify all patients with hereditary TTP in central Norway and to investigate the prevalence of hereditary TTP and the population frequencies of two common ADAMTS-13 mutations. Patients/Methods: Patients were identified in a cross-sectional study within the Central Norway Health Region by means of three different search strategies. Frequencies of ADAMTS-13 mutations, c.4143_4144dupA and c.3178C>T (p.R1060W), were investigated in a population-based cohort (500 alleles) and in healthy blood donors (2104 alleles) by taking advantage of the close neighborhood of the ADAMTS-13 and ABO blood group gene loci. The observed prevalence of hereditary TTP was compared with the rates of ADAMTS-13 mutation carriers in different geographical regions. Results: We identified 11 families with hereditary TTP in central Norway during the 10-year study period. The prevalence of hereditary TTP in central Norway was 16.7 x 10(-6) persons. The most prevalent mutation was c.4143_4144dupA, accounting for two-thirds of disease causing alleles among patients and having an allelic frequency of 0.33% in the central, 0.10% in the western, and 0.04% in the southeastern Norwegian population. The allelic frequency of c.3178C>T (p.R1060W) in the population was even higher (0.3-1%), but this mutation was infrequent among patients, with no homozygous cases. Conclusions: We found a high prevalence of hereditary TTP in central Norway and an apparently different penetrance of ADAMTS-13 mutations.