Characterization of patients with angioedema without wheals: the importance of F12 gene screening.
Sporadic and familiar forms of non-histaminergic angioedema and normal C1 inhibitor encompass a group of disorders possibly caused by bradikinin. We aimed to study the subgroups of hereditary angioedema with FXII mutation (FXII-HAE), unknown genetic defect (U-HAE) and idiopathic non-histaminergic acquired angioedema (InH-AAE). We screened the F12 locus in our cohort and delineated the clinical, laboratory and genetic features. Four families carried the p.Thr309Lys mutation in F12 gene. Haplotyping confirmed the hypothesis of a common founder. Six families were affected by U-HAE and 13 patients by sporadic InH-AAE. C4 levels were significantly lower in FXII-HAE than in InH-AAE. In the FXII-HAE group, none had attacks exclusively in high estrogenic states; acute attacks were treated with icatibant. Prophylaxis with tranexamic acid reduced the attack frequency in most patients. Our study provides new data on the diagnosis, clinical features and treatment of non-histaminergic angioedema, underlying the role of the screening for F12 mutations.
Department of Medical Sciences "M. Aresu", University of Cagliari, Italy. Electronic address: davide.firinu@unica.it.
Davide
D
Firinu
Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Valeria
V
Bafunno
Atherosclerosis and Thrombosis Unit, I.R.C.C.S. "Casa Sollievo della Sofferenza", S. Giovanni Rotondo, Foggia, Italy.
Gennaro
G
Vecchione
Department of Medical Sciences "M. Aresu", University of Cagliari, Italy.
Maria Pina
MP
Barca
Department of Medical Sciences "M. Aresu", University of Cagliari, Italy.
Paolo Emilio
PE
Manconi
Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Rosa
R
Santacroce
Medical Genetics, Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
Maurizio
M
Margaglione
Department of Medical Sciences "M. Aresu", University of Cagliari, Italy.
Stefano R
SR
Del Giacco
D000293:Adolescent; D000328:Adult; D000368:Aged; D000799:Angioedema / Q000188:drug therapy / Q000235:genetics / Q000276:immunology; D054179:Angioedemas, Hereditary / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D000933:Antifibrinolytic Agents / Q000627:therapeutic use; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists / Q000627:therapeutic use; D015331:Cohort Studies; D003181:Complement C4 / Q000276:immunology*; D005174:Factor XII / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D014148:Tranexamic Acid / Q000627:therapeutic use; D055815:Young Adult
D000933:Antifibrinolytic Agents; D065094:Bradykinin B2 Receptor Antagonists; D003181:Complement C4; D014148:Tranexamic Acid; C065679:icatibant; D005174:Factor XII; D001920:Bradykinin
Bradykinin; C1 inhibitor; F12; Factor XII; Normal C1-INH; U-HAE