Hereditary angioedema with normal C1 inhibitor: first report of an Argentinian family with factor XII mutation

ROZENFELD PA; FANTINI C; ZWIENER N

Conferencia; 11th C1‑inhibitor Deficiency & Angioedema Workshop; 2019

Hereditary angioedema with normal C1‑inhibitor: first report of an Argentinian family with factor XII mutationRicardo D. Zwiener1,*,Claudio Fantini2,Natalia Fili3,MónicaMaroco4,Paula Rozenfeld5Department of Allergy and Immunology, Austral University Hospital,Pilar, Buenos Aires, Argentina; 2 Department of Allergy and Immunology,HIGA Oscar Alende, Mar del plata, Argentina; 3 Department of Allergyand Immunology, Hospital Materno infantil, Salta, Argentina; 4 Departmentof Allergy and Immunology, Hospital Aeronáutico, Córdoba,Argentina; 5 IIFP, University of La Plata‑CONICET, La Plata, Buenos Aires,ArgentinaCorrespondence: Ricardo D. Zwiener (ricardozwiener@hotmail.com)Allergy, Asthma & Clinical Immunology 2019, 15(Suppl 4):O29Hereditary angioedema (HAE) is a rare genetic disease associated witheither a quantitative or qualitative deficiency in C1-inhibitor (C1-INH)or normal C1-INH. 1HAE with normal C1-INH levels could be caused by mutations in differentgenes. Until now, there are 3 known proteins whose genesmutations lead to HAE: F12 (HAE-FXII), plasminogen (HAEPLG) andangiopoietin 1 (HAEANGPT1). 2Approximately 30% of these cases are due to F12 gene (HAE-FXII)mutations. Point mutation (Thr328Lys or Thr328Arg), a large deletion(deletion of 72 base pairs: c.971_1018 + 24del72*) or an 18-bp duplicationin the F12 (FXII) gene are detected in HAE-FXII. 3A 42-year-old woman consulted for facial angioedema. She had 2 episodesof facial angioedema, that lasted 3 days and does not respondto treatment with corticosteroids and antihistamines, in the last2 years without any recognized trigger,. She referred frequent abdominalpain associated with diarrhea and one of them with hypotension. Adiagnosis of gastritis and irritable bowel diagnosis was provided.She was taking levothyroxine 50mcgs/day and contraceptives(drospirenone 3 mg, ethinyl estradiol 0.03 mg).She reported that her sister suffered from facial angioedema after adental procedure.After the suspicion of HAE, contraceptives were discontinued.Materials and methods: Serum, citrated plasma and EDTA-blood wascollected from the patients.Antigenic values of C4 and C1-INH was assayed by turbidimetric immunoassaysin serum samples from patients. Functional C1-INH activitywas assayed by a chromogenic assay in plasma samples from patients. Genetic test for F12 was assayed by sanger sequencing of exon 9 andintron?exon boundaries.Results: The results of quantitative and qualitative C4 (40.15 mg/dl),C1-INH (24.75 m/dl) and functional C1-INH (154%) were normal.Genetic test for F12 gene revealed the patient is heterozygous for thecommon missense mutation c.983C > A (p.Thr328Lys).All symptoms related to angioedema disappeared after contraceptivesdiscontinuation.After the confirmation of diagnosis of HAE of this patient, pedigreeanalysis in her family led to diagnosis of 2 other patients. Time to diagnosissince first symptom was 3 years.Conclusions: We described the first Argentinian family with mutationin F12 gene. Interestingly we found that the clinical episodes inthe case study are mild and are related to hormonal levels. All familymembers are less symptomatic than other types of HAE and the delayin diagnosis was 3 years.Consent to publish: Written, informed consent for publication wasobtained from the patient [or parent/guardian for patients under 16]