Validating and utilizing dried blood spots for family screening: Screening Programme Providing Outreach for Testing Hereditary Angioedema (SPPOT-HAE)

Background: Hereditary angioedema (HAE) is a rare genetic disorder with potentially life-threatening consequences, traditionally diagnosed by conventional laboratory methods that can be resource intensive and inconvenient. Incorporating dried blood spot (DBS) tests may be a promising alternative for diagnosing HAE and family screening.

Objective: This study aimed to validate DBS with conventional laboratory assays among confirmed C1 esterase inhibitor (C1-INH) HAE patients and assess the utility of DBS in a Screening Programme Providing Outreach for Testing Hereditary Angioedema (SPPOT-HAE).

Methods: In part 1, 16 Chinese C1-INH-HAE patients from 7 families participated in the validation of DBS for detecting C4, C1-INH, and functional C1-INH (fC1-INH). The results were compared with conventional laboratory assays. In part 2, DBS was utilized in family screening for HAE in a large Chinese family with relatives previously refusing testing.

Results: The study found strong correlation between conventional assays and DBS in measuring C4 (r = 0.870, P < .0001), C1-INH (r = 0.978, P < .0001), and fC1-INH (r = 0.756, P < .0001). There were no false-negative results from the DBS for C4, C1-INH or fC1-INH. SPPOT-HAE successfully recruited 9 additional relatives for family screening, of whom 22% were confirmed to have HAE. The use of DBS in an outreach program overcame barriers of prior family screening initiatives.

Conclusion: This is the first study to validate measurement of fC1-INH using DBS in C1-INH-HAE with conventional assays. An outreach program using DBS is a promising strategy overcoming previous barriers of family screening. Further large-scale, multicenter studies are required to establish the role of DBS, compare cost-effectiveness with prior strategies, and maximize diagnosis in resource-constrained countries.