Abstract
Background Inborn errors of metabolism (IEM) represent a subclass of rare inherited diseases caused by a wide range of defects in metabolic enzymes or their regulation. Of over a thousand characterized IEMs, only about half are understood at the molecular level, and overall the development of treatment and management strategies has proved challenging. An overview of the changing landscape of therapeutic approaches is helpful in assessing strategic patterns in the approach to therapy, but the information is scattered throughout the literature and public data resources.
Results We gathered data on therapeutic strategies for 299 diseases into the Drug Database for Inborn Errors of Metabolism (DDIEM). Therapeutic approaches, including both successful and ineffective treatments, were manually classified by their mechanisms of action using a new ontology.
Conclusions We present a manually curated, ontologically formalized knowledgebase of drugs, therapeutic procedures, and mitigated phenotypes. DDIEM is freely available through a web interface and for download at http://ddiem.phenomebrowser.net.
Footnotes
Abbreviations
- ChEBI
- Chemical Entities of Biological Interest
- DDIEM
- Drug database of inborn errors of metabolism
- DMR
- Data Mining and Repurposing
- ECO
- Evidence and Conclusion Ontology
- ERT
- Enzyme replacement therapy
- FAIR
- Findable, Accessible, Interoperable, Reusable
- FDA
- Food and Drug Administration
- GARD
- Genetic and Rare Diseases Information Center
- HPO
- Human Phenotype Ontology
- ICD
- International Classification of Diseases
- IEM
- Inborn errors of metabolism
- IRDiRC
- International Rare Diseases Research Consortium
- KEGG
- Kyoto Encyclopedia of Genes and Genomes
- MAxO
- Medical Action Ontology
- MPO
- Mammalian Phenotype Ontology
- NA
- Not available
- NCBI
- National Center for Biotechnology Information
- NIH
- National Institutes of Health
- OGMS
- Ontology for General Medical Science
- OMIM
- Online Mendelian Inheritance in Man
- OWL
- Web Ontology Language
- RAMEDIS
- Rare Metabolic Diseases Database
- RDF
- Resource Description Framework
- SRT
- Substrate reduction therapy
- SSIEM
- Society for the Study of Inborn Errors of Metabolism
- WHO
- World Health Organization