Exploratory analysis of genetic variation, clinical activity score, and lanadelumab response in two families with hereditary angioedema due to C1-inhibitor esterase deficiency

Background: Hereditary angioedema due to C1-inhibitor esterase (C1INH) deficiency is caused by mutations in the SERPING1 gene. The same mutation can cause variable disease severity, highlighting the role of genetic and clinical factors in disease expression. The aim of this study was to evaluate these factors alongside the effectiveness of lanadelumab in two families.

Case presentation: Here, we conducted a comparative analysis of affected members from two families including clinical activity scores, C1INH activity levels at diagnosis and genetic mutations. In lanadelumab treated patients, efficacy was evaluated three and 12 months post-initiation, and the two groups were compared. In family 1, eight affected individuals were identified across five generations. A deletion in exon 4 was detected in three of the six living patients. The clinical activity score was ≥5 in all and the C1INH activity level ≤ 40 % in five of them. In the three sisters receiving lanadelumab, the uncontrolled disease became a controlled one. In family 2, 16 affected individuals were identified across four generations, with eight patients followed at our center. A missense mutation in exon 8 was detected in five patients. Un undetectable C1INH activity level and clinical activity scores ≥5 was identified in five patient. In two from the three patients treated with lanadelumab a markedly reduction in attacks frequency weas obtained (from 9 to 2 in both of them) and one patient became symptom-free.

Conclusions: The relationship between specific genetic mutations, clinical severity score, and response to prophylactic treatment remains inconclusive.