Autistic alterations: Metabolic shifts in children with autism spectrum disorders

Diagnosing autism spectrum disorders

The term autism spectrum disorders (ASD) covers a range of developmental brain disorders which are often referred to simply as autism. They include classic autism, Asperger syndrome, Rett syndrome, childhood disintegrative disorder and the more general disorder known as pervasive developmental disorder not otherwise specified. Each of these can strike with different degrees of severity with a wide range of symptoms.

Diagnosis of ASD is based on behavioural tests but it can be overlooked at first because parents, teachers and doctors might regard it merely as a slower than average development, thinking that the child will soon catch up to its peers. Another diagnostic option might be found in the future using a clinical test because the metabolism of children with ASD is affected in several ways.

For instance, some amino acids are known to have reduced levels in the urine, plasma, and cerebrospinal fluid of ASD patients. The metabolisms of purine and some organic acids and fatty acids are also affected in some children with ASD. In addition, discrepancies in the metabolism of the gut have been observed in ASD, with atypical populations of bacteria.

A team of scientists in the US, with lead reporter Xue Ming from the University of Medicine and Dentistry of New Jersey, has now undertaken a full metabolomics study of children with ASD. They hoped to provide further insight into the development and metabolism of the condition. If the metabolic perturbations can be characterised fully, it is possible that they could be used to devise a diagnostic test. At the very least, more complete knowledge will lead to new treatments by improving gastrointestinal behaviour through dietary management. It has already been reported that changes in diet have improved the behaviour of children with ASD.

Metabolic movements in autism

Spot urine samples were collected from 48 children with ASD and 53 age-matched controls and subjected to a sequential solvent extraction scheme before analysis by GC/MS with electron ionisation and LC-tandem-MS with electrospray ionisation in positive-ion and negative-ion modes to detect basic and acidic species.

The combined approach identified a total of 391 urinary metabolites of which 82 displayed altered abundances between the ASD and normal children, 53 being more abundant and 29 less abundant. The differences were unaffected by gender, diet, medication and supplements. The most striking variations belonged to metabolites in three metabolic areas: amino acid metabolism, antioxidant status and gut bacterial metabolism.

The amino acids glycine, serine, threonine, alanine and histidine were all at lower levels in the ASD children but the researchers were unable to deduce why. γ-Glutamyl amino acids were also at reduced levels, possibly as a result of increased activity of the enzyme γ-glutamyl transferase which points to liver damage, perhaps as a consequence of medication.

Increased oxidative stress has been reported in ASD children and this is backed up in the current study by reduced levels of the antioxidants carnosine and urate. Carnosine therapy has been shown to improve ASD patients.

A number of gut metabolites were also affected by ASD, some like taurocholenate sulphate being increased and others, like 5-aminovalerate, being decreased. However, these changes only affected those children who exhibited symptoms of gastrointestinal dysfunction like constipation and diarrhoea. ASD children who showed no such symptoms had gut bacterial metabolisms similar to those of controls.

Excess microbial growth in the gut of ASD children is well reported and the altered metabolism could be intrinsic to ASD pathogenesis, although the exact mechanisms are unclear. "It is possible that our results of increased levels of bacterial co-metabolites represent an overproduction of the bacterial metabolites due to bacterial imbalance, increased absorption of the metabolites due to increase intestinal mucosa permeability to small molecules, or both," declared Ming.

The new data shed further light on the metabolic processes associated with ASD but more detailed studies are required, especially into the role of the gut microbes.