BackgroundIntellectual disability (ID) is a devastating and frequent condition, affecting 2-3% of the population worldwide. Early recognition of treatable underlying conditions drastically improves health outcomes and decreases burdens to patients, families and society. Our systematic literature review identified 81 such inborn errors of metabolism, which present with ID as a prominent feature and are amenable to causal therapy. The WebAPP translates this knowledge of rare diseases into a diagnostic tool and information portal.Methods & resultsFreely available as a WebAPP via http://www.treatable-id.org and end 2012 via the APP store, this diagnostic tool is designed for all specialists evaluating children with global delay / ID and laboratory scientists. Information on the 81 diseases is presented in different ways with search functions: 15 biochemical categories, neurologic and non-neurologic signs & symptoms, diagnostic investigations (metabolic screening tests in blood and urine identify 65% of all IEM), therapies & effects on primary (IQ/developmental quotient) and secondary outcomes, and available evidence For each rare condition a ‘disease page’ serves as an information portal with online access to specific genetics, biochemistry, phenotype, diagnostic tests and therapeutic options. As new knowledge and evidence is gained from expert input and PubMed searches this tool will be continually updated. The WebAPP is an integral part of a protocol prioritizing treatability in the work-up of every child with global delay / ID. A 3-year funded study will enable an evaluation of its effectiveness.ConclusionsFor rare diseases, a field for which financial and scientific resources are particularly scarce, knowledge translation challenges are abundant. With this WebAPP technology is capitalized to raise awareness for rare treatable diseases and their common presenting clinical feature of ID, with the potential to improve health outcomes. This innovative digital tool is designed to motivate health care providers to search actively for treatable causes of ID, and support an evidence-based approach to rare metabolic diseases. In our current –omics world with continuous information flow, the effective synthesis of data into accessible, clinical knowledge has become ever more essential to bridge the gap between research and care.

Intellectual Disability (ID) affects 2.5% of the population worldwide. This life-long disability manifests before the age of 18 years, and is characterized by significant limitations in intellectual functioning (IQ<70) as well as in adaptive behavior, which comprises conceptual, social and practical skills 1 . If formal testing is unavailable, school report cards, direct clinical observation and reports of third party informants are used to determine the presence of ID. In children under five years-ofage, IQ tests are not deemed reliable, and the term 'global developmental delay' is used, defined by significant limitations of two or more developmental domains (e.g. fine/gross motor skills, speech/language, cognition, social/personal, activities of daily living), i.e. a performance of two standard deviations or more below the mean on age-appropriate, standardized, normreferenced testing 2 . Here we apply ID as collective term for both. Affecting all areas of a patient's life, ID results in considerable ABSTRACT: Background: Identification of the underlying cause of intellectual disability (ID) is important as it improves genetic counselling, management, adaptation; yet its etiologic heterogeneity is challenging and often leads to an expensive work-up. Methods: To improve this diagnostic trajectory, the multidisciplinary Complex Diagnostic Clinic (CDC) was established for ID patients with unexplained complex systemic and/or neurologic features that were referred to the CDC and evaluated by three medical specialists followed by multi-disciplinary rounds. Analyses included surveys and interviews, (retrospective) chart review, costs calculations and comparison. Results: 24 children (9 male) were evaluated during seven clinics held over 16 months. The average patient age was 7 years 11 months (range 9 months-18 years). All the children had previously been seen by 2-10 specialist services. The diagnostic yield of the CDC was higher than expected with confirmed and working diagnoses in 11 (46%) and 9 (38%) children respectively. Cost-savings included fewer trips to hospital and fewer tests via more streamlined evaluations. Positive feedback was received from both families and medical professionals. Conclusions: The CDC represents an innovative model of personalized care. Specialist collaboration in the interpretation of relevant clinical, biochemical and genomic data resulted in diagnoses, where none had previously been possible. RÉSUMÉ: Valeur diagnostique d'une clinique multidisciplinaire pour la déficience intellectuelle.Contexte : L'identification de la cause de la déficience intellectuelle (DI) est importante parce qu'elle permet d'améliorer le conseil génétique, le traitement et l'adaptation du patient. Cependant, l'hétérogénéité de la DI explique que son diagnostic demeure un défi et donne souvent lieu à des examens coûteux. Méthode : La clinique multidisciplinaire pour le diagnostic de maladies complexes (CMDMC) a été établie afin d'améliorer le parcours diagnostique pour les patients atteints de DI qui ont des...