Hereditary Angioedema: Role of Genetic Test in Diagnosis

MARTINEZ P; ROZENFELD P

Congreso; XXVI Congress of the International Society on Thrombosis and Haemostasis; 2017

?Laboratory tests for the diagnosis of HAE in Argentina are underdeveloped. Most patients are diagnosed with C1-INH tests, but for patients with high clinical suspicion of HAE and normal test for C1-INH, testing for mutations in the Factor XII (FXII) gene may allow diagnosis in some patients.Aims: ?To show the outcomes of patients diagnosed in Argentina with hereditary angioedema (HAE) and the utility of genetic tests results.Methods: ?Patients and samples: A total of 587 patients with clinical suspicion of HAE were studied.?Quantification of complement factors: serum samples are collected to measure C3, C4 and C1-INH levels using a turbidimetric method. Spectrophotometric assays are used to measure the functional activity of C1-INH.?SERPING1 genetic test: involves isolation of patients' DNA and sequencing of PCR-amplified exons 1-8 and the underlying intronic regions.?FXII genetic test: the most common mutation c.983C>A in exon 9.Results: A total of 587 samples were received and 144 (24.5%) patients were diagnosed,125 (21.3%) patients with HAE type 1 (HAE 1), 15 (2.5%) type 2 (HAE II) and 4 (0.7%) with normal C1 inhibitor (HAE-nC1).SERPING1 genetic test: A genetic test was performed in 23 families and confirmed HAE I/II. Forty-two percent mutations were consistent with the common mutation c.1031-20a>g. No mutation was found in the coding region in 2 cases.FXII genetic test: This test was only performed in patients with strongly clinically suspected HAE, but functional C1-INH was normal. Four out of the 14 tested patients had the FXII mutation (28%), thereby confirming HAE diagnosis based on mutations in FXII gene.Conclusions: A total of 587 samples were received and 144 patients were diagnosed. Mutations of the SERPING1 gene were found in 91% of patients. HAE-nC1 was diagnosed based on the FXII mutation gene in 28% of patients with normal C1-INH function, being important in the diagnostic algorithm.