Red blood cell fatty acid compositions in a patient with autistic spectrum disorder: a characteristic abnormality in neurodevelopmental disorders?

Abstract:

The fatty acid compositions of red blood cell (RBC) phospholipids from a patient with autistic spectrum disorder (ASD) had reduced percentages of highly unsaturated fatty acids (HUFA) compared to control samples.

The percentage of HUFA in the RBC from the autistic patient was dramatically reduced (up to 70%) when the sample was stored for 6 weeks at -20 degrees C. However, only minor HUFA reductions were recorded in control samples stored similarly, or when the autistic sample was stored at -80 degrees C.

A similar instability in RBC HUFA compositions upon storage at -20 degrees C has been recorded in schizophrenic patients. In a number of other neurodevelopmental conditions, including attention deficit hyperactivity disorder (ADHD) and dyslexia, reduced concentrations of RBC HUFA have been recorded.

The extent and nature of these aberrations require further assessment to determine a possible common biochemical origin of neurodevelopmental disorders in general. To facilitate this, a large scale assessment of RBC fatty acid compositions in patients with ASD, and related disorders, should be performed as a matter of urgency.

Supplementing cells in culture with the tryptophan metabolite indole acrylic acid (IAA) affected the levels of cellular HUFA and prostaglandin production. Indole acroyl glycine (IAG), a metabolite of IAA excreted in urine, is found in high concentrations in patients with neurodevelopmental disorders including ASD, ADHD, dyslexia, Asperger's syndrome and obsessive compulsive disorder.

NON-TECHNICAL SUMMARY

• Highly unsaturated fatty acids (HUFA) of the omega-3 and omega-6 series are essential for normal brain development and function. They are an important element of brain cell membranes, normally making up around 20% of the brain's dry mass.

• Concentrations of HUFA in red blood cell (RBC) membranes can provide an index of fatty acid status, although care needs to be taken in the preparation and analysis of blood samples because HUFA are highly perishable.

• In most cases, storage of samples at only -20 degrees C does not lead to significant deterioration in the HUFA content of red blood cells over short time periods such as 6 weeks. However, as this paper reports, dramatic reductions of up to 70% in RBC HUFA were found in samples from an autistic individual when stored under these conditions. When frozen at a much lower temperature (-80 degrees C) the loss of HUFA in samples from this autistic individual were minimal and comparable with controls.

• Although this is this first report of such fragility of membrane HUFA in autism, a similar instability of HUFA in RBC membranes has previously been recorded in patients with schizophrenia. Like other evidence, this suggests that similar biochemical abnormalities may contribute to a range of different neurodevelopmental conditions.

• This paper also reports on a preliminary investigation of possible links between fatty acid status and an unusual substance (IAG) commonly found in urine from autistic subjects. This is likely to arise from the breakdown of another substance, IAA. (This may be created by abnormal processing of the amino acid tryptophan, which can otherwise be used to make the neurotransmitter serotonin). When IAA was added to cells in culture, it affected both membrane HUFA concentrations and the production of prostaglandins from these. These results are of interest because they offer a possible link between two different biochemical abnormalities in autism.