Hereditary Angioedema (HAE) with a mutation in the plasminogen gene: a retrospective study of a cohort of 14 patients from Russia

BACKGROUND: In 2018, a new form of hereditary angioedema without C1-inhibitor deficiency — hereditary angioedema with a mutation in the plasminogen gene — was identified. The world scientific literature describes a small number of patients with this form of the disease and, therefore, new research is relevant. AIMS: To identify the sociodemographic and clinical features of patients with hereditary angioedema with plasminogen gene mutation; to evaluate the treatment efficacy; to conduct a comparative analysis in a group of patients with hereditary angioedema type I/II. MATERIAL AND METHODS: 14 patients (1 male and 13 females, mean age 51.64±13.55 years) with hereditary angioedema with c.988A>G mutation in the plasminogen gene (p.Lys330Glu; K330E) were enrolled in a retrospective study. The comparison group included 194 patients with hereditary angioedema type I/II (56 males and 138 females, mean age 37.03±16.23 years). RESULTS: The average age at disease onset in patients with hereditary angioedema with a mutation in the plasminogen gene is 25.07±10.46 years, which is significantly higher than in patients with hereditary angioedema type I/II — 11.58±8.92 years ( p <0.001). Peripheral angioedema was reported in 21.4% of patients with hereditary angioedema with a mutation in the plasminogen gene, abdominal attacks in 28.6%, which is less common than in patients with hereditary angioedema type I/II (peripheral edema 97.4%, p <0.001; abdominal attacks 86.6%, p <0.001). Face and neck angioedema was observed in all patients with hereditary angioedema with a mutation in the plasminogen gene (100%) and in 72.2% of patients in the group of hereditary angioedema type I/II ( p =0.023). 85.7% of patients with hereditary angioedema with a mutation in the plasminogen gene had edema of the tongue. A decrease in the severity and duration of 28 out of 29 attacks by an average of 71.4% was reported by 4/5 of patients who used icatibant (Firazyr); 3/4 of patients reported a decrease in the frequency of attacks during treatment with tranexamic acid. CONCLUSIONS: The disease’s manifestation in adulthood, the predominance of face and tongue angioedema are common features of hereditary angioedema with a mutation in the plasminogen gene. The efficacy of tranexamic acid and icatibant was demonstrated in the observed cohort of patients.