DDIEM: drug database for inborn errors of metabolism

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 300 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.

Child and Adolescent Psychiatrists’ Use, Attitudes, and Understanding of Genetic Tests in Clinical Practice

“…Genetic testing is currently part of the standard of care in the evaluation of children and adults for some neuropsychiatric conditions, including autism spectrum disorder (ASD) 7–9 and intellectual and developmental disorders (IDD) 9,10 , where results can impact subsequent medical decision making 9,11,12 ; (e.g. detecting inborn errors of metabolism can lead to specific treatments 13 , and genetic diagnoses can trigger screening and follow up for associated medical conditions 9,12 . Numerous professional organizations recommend genetic testing to evaluate ASD, but implementation remains low 11,14,15 .…”

Food or medicine? A European regulatory perspective on nutritional therapy products to treat inborn errors of metabolism

“…9 A limited number of nutritional therapy products is formally authorized as medication. 3,10 Additionally, specifically designed amino acid mixtures are available as special medical foods to supply patients with sufficient amounts of amino acids without the amino acid of which the metabolism is affected (e.g., Phe-free amino acid mixtures for PKU). 8,11 The lack of consistent terminology and clear delineation within the regulatory landscape hinders the discourse pertaining to the availability and accessibility of suitable nutritional therapy products required for the management of IEMs in current clinical practice.…”

“…Single nutrients, like the aforementioned vitamins and single amino acids or co‐enzymes, are available in the form of supplements 9 . A limited number of nutritional therapy products is formally authorized as medication 3,10 . Additionally, specifically designed amino acid mixtures are available as special medical foods to supply patients with sufficient amounts of amino acids without the amino acid of which the metabolism is affected (e.g., Phe‐free amino acid mixtures for PKU) 8,11 .…”

Applications of quantitative metabolomics to revolutionize early diagnosis of inborn errors of metabolism in India

“…Ever since the realization of IEMs as manifestations of biochemical individuality by Garrod, 5 there is great progress in our understanding of these rare disorders. The list of IEMs has grown substantially in recent decades, amounting to ≥7000 individual conditions 6 . The cumulative incidence of the widely studied ∼1000 disorders was estimated to be ∼1:800 7,8 …”

“…The list of IEMs has grown substantially in recent decades, amounting to ≥7000 individual conditions. 6 The cumulative incidence of the widely studied ∼1000 disorders was estimated to be ∼1:800. 7,8 As a standard preventive strategy, newborn screening (NBS) programs have been instituted in developed countries like the USA, Canada, Australia, Japan, New Zealand, and a few European countries.…”