The investigation of inborn errors of metabolism as an underlying cause of idiopathic intellectual disability in adults in Norway

Eur J Neurol. 2016 Jan:23 Suppl 1:36-44. doi: 10.1111/ene.12884.

Abstract

Background and purpose: Inborn errors of metabolism (IEMs) may be an unrecognized cause of intellectual disability (ID) in adults. Knowledge and techniques for investigating IEMs have evolved rapidly; therefore adult patients with idiopathic ID may benefit from an up-to-date aetiological work-up. This review aims at establishing recommendations for investigating IEMs as a cause of ID in adults.

Methods: PubMed was searched for articles published between 2000 and 2015 regarding clinical work-up, IEMs, ID and adults. Information compiled from 61 articles is used to give practical suggestions from a clinical point of view.

Results: Many IEMs that cause ID are characterized by increased risk of specific somatic, neurological and psychiatric signs. Neurometabolic investigations of ID should start with a thorough medical history, clinical examination and general screening in blood. Brain imaging with magnetic resonance imaging and if possible magnetic resonance spectroscopy should also be part of the initial work-up. The aim is to detect abnormalities that give clues to a specific IEM. After the initial screening, a first tier of neurometabolic screening tests in blood and urine should be performed. If this fails to give diagnostic clues, a second tier of neurometabolic tests should be considered in order to secure that the treatable IEMs are detected. Whole exome sequencing techniques, when they become available in clinical settings, will offer new opportunities for detection of IEMs.

Conclusion: Based on a broad review of the current literature a systematic diagnostic work-up to detect IEMs as a cause of ID in adults is suggested.

Keywords: cognitive function; diagnostic examination; inborn errors of metabolism; intellectual disability; mental retardation; neurological.

Publication types

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

MeSH terms

  • Adult
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / epidemiology
  • Intellectual Disability / etiology*
  • Metabolism, Inborn Errors / complications*
  • Metabolism, Inborn Errors / diagnosis*
  • Metabolism, Inborn Errors / epidemiology
  • Norway / epidemiology