In FD, the scoring system was shown to have 95.5% sensitivity for males at increased or possible risk and a 76.8% sensitivity for females at increased or possible risk. There was 100% specificity for increased risk against the negative control population (Gaucher disease). In HAE there was a 98.6% sensitivity for individuals at increased risk or possible risk of HAE (including those with ACE inhibitor induced angioedema). There was 99% specificity against the negative control group (multifactorial edema) for increased risk.
Introduction: Rare genetic conditions are notorious for being excluded from differential diagnosis of nongenetic specialists. This delay in diagnosis can lead to poorer health outcomes for patients and delay in treatment initiation. For example, Fabry disease has a median duration diagnostic delay of 10.5-21 years and studies have shown that early initiation with FDA approved therapies lead to optimal outcomes. A pilot study in two genetic conditions was undertaken to determine if patients who may be at risk to have an underlying genetic condition can be flagged from deidentified medical records data fields. Hypothesis: An automated severity scoring system can be used to screen patients at possible increased risk for Fabry disease (FD) or Hereditary Angioedema (HAE) with high sensitivity and specificity. Methods: In this study an automated severity scoring system was created to score individuals as increased, possible, or no increased risk of FD or HAE. This system was validated using published cases and anonymous patient data sets as positive controls and phenocopies as negative controls. Results: 40th Annual Conference | September 22-26, 2021 | Virtual Event Validation: In FD, the scoring system was shown to have 95.5% sensitivity for males at increased or possible risk and a 76.8% sensitivity for females at increased or possible risk. There was 100% specificity for increased risk against the negative control population (Gaucher disease). In HAE there was a 98.6% sensitivity for individuals at increased risk or possible risk of HAE (including those with ACE inhibitor induced angioedema). There was 99% specificity against the negative control group (multifactorial edema) for increased risk. Screening: An initial test run of the scoring system for HAE was conducted on de-identified records of 298,288 patients. The screening algorithm identified 297 patients as possible risk and 7 as increased risk for HAE. The algorithm identified 2 patients with a known family history of HAE, 2 individuals treated with HAE-specific medications, 54 individuals with low serum C4, and 241 individuals ACE inhibitor induced angioedema. Conclusion: The screening algorithms were found to have high sensitivities for FD and HAE as well as high specificities against the control groups. These results suggest that development, validation and implementation of automated severity scoring systems such as these can be useful screening tools to aid providers in identifying patients at risk for rare genetic conditions. Further studies are currently being conducted to implement screening algorithms in a regional medical center.
| Poster Number: | UM353 |
| Event: | 2021 - NSGC Annual Conference |
| Author(s): | Dawn Laney, Jessica Dronen |
| Affiliation(s): | ThinkGenetic Foundation; Emory Univesity, ThinkGenetic, Inc. |
| Link: | https://www.nsgc.org/Portals/0/Docs/AnnualConference/Abstracts/2021/2021%20Abstract%20Document_docx.pdf?ver=9YDQsIg0bRXEO3di8-MbqQ%3d%3d |
| Poster: | Array |
