JMIR Publications

ABSTRACT

Background:

Hereditary angioedema (HAE) is a rare genetic condition caused by C1 esterase inhibitor deficiency, dysfunction, or kinin cascade dysregulation, causing an increased bradykinin plasma concentration. HAE is a poorly recognized clinical entity and is very often misdiagnosed as a histaminergic angioedema. Despite its genetic nature, a first-line genetic screening is not integrated in the routine diagnosis. Consequently, a delay in the diagnosis and inaccurate or incomplete diagnosis or treatment of HAE are common.

Objective:

In agreement with recent recommendations from the International Consensus on the Use of Genetics in the Management of HAE, in order to assist the clinical diagnosis and adapt it to the paradigm of precision medicine and Next-Generation Sequencing based genetic tests, we have developed the Hereditary Angioedema Database Annotation (HADA) tool.

Methods:

HADA is built on top of a database of hundreds of known variants affecting function, including precomputed pathogenic assessment of each variant and a ranked classification according to the current guidelines from the American College of Medical Genetics and Genomics.

Results:

HADA is provided as a free accessible user-friendly web-based interface with versatility for the entry of genetic information. The underlying database can be also incorporated into automated command-line stand-alone annotation tools.

Conclusions:

Our tool can perform a rapid detection of variants affecting function for the different HAE types, as well as integrates useful information to reduce the diagnosis odyssey and improve its delay.