The metabolic evaluation of the child with an intellectual developmental disorder: diagnostic algorithm for identification of treatable causes and new digital resource

Mol Genet Metab. 2014 Apr;111(4):428-38. doi: 10.1016/j.ymgme.2014.01.011. Epub 2014 Jan 24.


Intellectual developmental disorders (IDD), characterized by significant impairment of cognitive functions, with limitations of learning, adaptive behavior and skills, are frequent (2.5% of the population affected) and present with significant co-morbidity. The burden of IDD, in terms of emotional suffering and associated health care costs, is significant; prevention and treatment therefore are important. A systematic literature review, updated in 2013, identified 89 inborn errors of metabolism (IEMs), which present with IDD as prominent feature and are amenable to causal therapy. Therapeutic effects include improvement and/or stabilization of psychomotor/cognitive development, behavior/psychiatric disturbances, seizures, neurologic and systemic manifestations. The levels of available evidence for the various treatments range from Level 1b, c (n=5); Level 2a, b, c (n=14); Level 4 (n=53), and Levels 4-5 (n=27). For a target audience comprising clinical and biochemical geneticists, child neurologists and developmental pediatricians, five experts translated....this data into a 2-tiered diagnostic algorithm: The first tier comprises metabolic "screening" tests in urine and blood, which are relatively accessible, affordable, less invasive, and have the potential to identify 60% of all treatable IEMs. The second tier investigations for the remaining disorders are ordered based on individual clinical signs and symptoms. This algorithm is supported by an App, which comprises up-to-date information on all 89 IEMs, relevant diagnostic tests, therapies and a search function based on signs and symptoms. These recommendations support the clinician in early identification of treatable IEMs in the child with IDD, allowing for timely initiation of therapy with the potential to improve neurodevelopmental outcomes. The need for future studies to determine yield and usefulness of these recommendations, with subsequent updates and improvements to developments in the field, is outlined.

Keywords: Algorithm; App; Cognition; Diagnosis; Inborn errors of metabolism; Treatable.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Algorithms
  • Child
  • Costs and Cost Analysis
  • Developmental Disabilities / diagnosis*
  • Developmental Disabilities / economics
  • Developmental Disabilities / therapy
  • Health Planning Guidelines
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / economics
  • Intellectual Disability / therapy
  • Internet*
  • Metabolism, Inborn Errors / diagnosis
  • Metabolism, Inborn Errors / economics
  • Metabolism, Inborn Errors / therapy