Screening for type II hereditary angioedema—the “poor man’s c1-inhibitor function”

Abstract

<h3>Background</h3><p>Hereditary angioedema (HAE) is a rare genetic disease. Patients with type II HAE have normal or elevated C1-inhibitor (C1-INH) levels but C1-INH protein is dysfunctional. C1-INH function requires careful sample handling and technical expertise and may account for the lack of diagnosed patients with type II HAE in resource-limited countries.</p><h3>Objective</h3><p>We sought to assess the diagnostic performance of elevated C1-INH levels in diagnosing type II HAE.</p><h3>Methods</h3><p>All patients with confirmed type II HAE in Hong Kong and India were analyzed. Diagnosis was confirmed by persistent low C1-INH function and/or pathogenic <em>SERPING1</em> gene mutations. Their C1-INH levels were compared with those of matched controls.</p><h3>Results</h3><p>A total of 31 (14 Chinese, 17 Indian) patients with type II HAE and 31 matched controls were analyzed. Overall, 77.4% (24/31) of patients with type II HAE had elevated C1-INH levels compared with 38.7% (12 of 31) of controls (odds ratio, 2.00; 95% CI, 1.34-2.98; <em>P</em> = .017). C1-INH levels in patients with type II HAE were significantly higher than in controls (52.2 ± 20.0 mg/dL vs 29.1 ±3.6 mg/dL; <em>P</em> < .001). Findings were consistent when C1-INH values in the Chinese and Indian subgroups were analyzed separately. Receiver-operating characteristic curve demonstrated excellent performance for elevated C1-INH levels to diagnose patients with type II HAE with an area under the curve of 0.953 (95% CI, 0.941-0.992; <em>P</em> < .001). Positive and negative predictive values of both a low C4 and an elevated C1-INH level for patients with type II HAE were 100% and 82.9%, respectively.</p><h3>Conclusions</h3><p>Low C4 and elevated C1-INH levels may be considered as a screening tool for type II HAE, especially in countries where C1-INH function testing is not readily available.</p><h2>Key words</h2>