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.