Diagnostic delay, SERPING1 allelic heterogeneity, and real-world lanadelumab prophylaxis in Chinese patients with hereditary angioedema due to C1 inhibitor deficiency.

BACKGROUND: Hereditary angioedema due to C1 inhibitor deficiency (HAE-C1INH) is a rare and potentially life-threatening bradykinin-mediated disorder most commonly associated with pathogenic variants in SERPING1. Data from Chinese patients remain limited, particularly regarding diagnostic delay, SERPING1 allelic heterogeneity, and real-world use of lanadelumab prophylaxis. METHODS: In this single-center retrospective observational study, we reviewed 10 consecutive unrelated index patients with confirmed HAE-C1INH managed at Henan Provincial People's Hospital from January 2022 to May 2026. Clinical data, complement results, and SERPING1 Sanger sequencing findings were analyzed. Variants were classified according to ACMG/AMP criteria. Seven patients received lanadelumab long-term prophylaxis. Annualized attack rates and Angioedema Control Test scores before and during prophylaxis were compared using the Wilcoxon signed-rank test. RESULTS: The cohort included 6 females and 4 males, with a mean age of 32.8 ± 9.9 years. Nine patients had HAE-C1INH type 1 and one had type 2. The mean age at symptom onset was 21.7 ± 11.1 years, and the mean diagnostic delay was 9.4 ± 7.0 years. All patients had recurrent peripheral edema, 7 had abdominal attacks, and 6 had facial and/or laryngeal involvement. One patient required emergency tracheotomy. Serum C4 was reduced during attacks in all patients, and C1q levels were normal. Ten distinct heterozygous SERPING1 variants were identified, including 3 frameshift variants, 6 missense variants, and 1 in-frame deletion. Among the 7 patients receiving lanadelumab, the median annualized attack rate decreased from 11 (IQR, 7-23) to 0 (IQR, 0-1) attacks/year, and the median AECT score increased from 3 (IQR, 2-4) to 13 (IQR, 13-13). No serious adverse events were recorded. CONCLUSIONS: This single-center retrospective study showed substantial diagnostic delay, marked SERPING1 allelic heterogeneity, and favorable real-world outcomes with lanadelumab prophylaxis in Chinese patients with HAE-C1INH. Earlier complement testing and access to appropriate genetic testing may shorten diagnostic delay. Larger prospective studies are needed to define individualized long-term prophylaxis strategies in Chinese patients.