Article Text

  1. J V Leonard1
  1. 1Clinical and Molecular Genetics, UCL Institute of Child Health, London, UK


Metabolic disorders are a rare cause of acute encephalopathy in childhood but are nevertheless important because many are treatable. Both morbidity and mortality can be prevented but in most cases the diagnosis needs to be early. Although there are many disorders, investigations can be simplified but the results of these tests are almost always needed urgently. With the expansion of neonatal screening programmes, more patients will already have been diagnosed, but it is important to recognise that patients may still be missed. Therefore it is essential that there is continued vigilance for these disorders. Many will also still be at risk of recurrent episodes of illness and decompensation.

The mechanisms of encephalopathy in many disorders are not well understood but two deserve special mention; hyperammonaemia and organic acidaemias.

Hyperammonaemia secondary to urea cycle disorders has a high morbidity and mortality. There is now increasing evidence that the accumulation of glutamine within astrocytes is the primary event although other factors are also still important. Reducing plasma ammonia and glutamine concentrations is the key goal to improving the outcome.

In organic acidaemias the mechanisms of acute neurological insults have long been a puzzle but there is now good evidence that, in certain disorders, dicarboxylic acids produced within the brain become trapped there. The concentrations may rise to toxic concentrations without similar changes systemically. Strategies to prevent this include inhibiting the uptake of precursor amino acids and providing substrates for energy, notably glucose. Understanding the aetiology should improve the long-term outcome.

Statistics from

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.