Knowledge base and mini-expert platform for the diagnosis of inborn errors of metabolism

Abstract

Purpose: Recognizing individuals with inherited diseases can be difficult because signs and symptoms often overlap those of common medical conditions. Focusing on inborn errors of metabolism (IEMs), we present a method that brings the knowledge of highly specialized experts to professionals involved in early diagnoses. We introduce IEMbase, an online expert-curated IEM knowledge base combined with a prototype diagnosis support (mini-expert) system.Methods: Disease-characterizing profiles of specific biochemical markers and clinical symptoms were extracted from an expert-compiled IEM database. A mini-expert system algorithm was developed using cosine similarity and semantic similarity. The system was evaluated using 190 retrospective cases with established diagnoses, collected from 15 different metabolic centers.Results: IEMbase provides 530 well-defined IEM profiles and matches a user-provided phenotypic profile to a list of candidate diagnoses/genes. The mini-expert system matched 62% of the retrospective cases to the exact diagnosis and 86% of the cases to a correct diagnosis within the top five candidates. The use of biochemical features in IEM annotations resulted in 41% more exact phenotype matches than clinical features alone. Conclusion:IEMbase offers a central IEM knowledge repository for many genetic diagnostic centers and clinical communities seeking support in the diagnosis of IEMs.

Cross-platform genetic discovery of small molecule products of metabolism and application to clinical outcomes

“…Using a binomial two-tailed test, enrichment of metabolic loci was assessed by comparing the annotated list with the full list of 784 IEM genes in Orphanet against a backdrop of 19,817 protein-coding genes 51 . IEM-annotated loci for which the associated metabolite matched or was closely biochemically related to the IEM corresponding metabolite(s) based on IEMBase 52 were considered further for analysis.…”

DDIEM: Drug Database for Inborn Errors of Metabolism

“…However, neither provide information on the mechanism of drug mechanism or on the phenotypes corrected or alleviated. Another database, IEMbase [10], provides some therapeutic information but concentrates mainly on the clinical and biochemical aspects of rare metabolic disease, and provides an expert platform to facilitate their early and accurate diagnosis. To the best of our knowledge, DDIEM is the first database that significantly focuses on the treatment either used or investigated, to correct or alleviate phenotypes associated with the course of a specific metabolic disease.…”

Epilepsy in selected neurometabolic diseases

“…13. Fenotyp postępującej padaczki mioklonicznej w okresie młodzieńczym Postulowane mechanizmy patogenetyczne padaczki o podłożu metabolicznym są następujące [5][6][7][8][9][10][11][12]:…”