Cascade Screening of Hereditary Angioedema in Pakistan.

Abstract

Objective: To establish cascade family screening of newly diagnosed hereditary angioedema (HAE) patients.

Study design: Cross-sectional, observational study. Place and Duration of the Study: Department of Immunology, The Armed Forces Institute of Pathology / CMH / NUMS, Rawalpindi, Pakistan, from September 2021 to June 2024.

Methodology: Eighty-nine parents, siblings, and children of 10 diagnosed patients of HAE were screened. Thirty-two family members were screened by using C1 esterase and complement C4 levels, whereas 57 patients were not available or willing for blood samples, and a questionnaire designed for HAE was recorded from patients / index cases. Baseline characteristics of HAE-Index and HAE-Screened patients were analysed using inferential statistics (independent t-test, Chi-square / Fisher's exact, and Mann-Whitney U test), selected based on data distribution (assessed by the Shapiro-Wilk's test).

Results: A total of 10 cases were followed for screening in families. Upon cascade screening of 89 individuals, 16 confirmed and 24 probable cases of HAE among family members (symptomatic and asymptomatic) were identified. Out of these 40 positive patients, 26 were male and 14 were female. Three patients among these screened individuals died secondary to laryngeal oedema. Out of ten index cases, two did not have any family history of hereditary angioedema, hence suspected for de novo mutation in the SERPING-1 gene.

Conclusion: Cascade screening helps in facilitating early diagnosis of asymptomatic or mildly symptomatic family members of HAE patients. This will provide better guidance for avoiding potential triggers, appropriate prophylaxis, and better management of HAE patients. Young patients of HAE need genetic counselling for a 50% risk of HAE in offspring and are recommended for prenatal diagnosis.

Key words: C1 esterase, C4, Hereditary angioedema, Laryngeal oedema, Screening.