Tuesday, 14 June 2011

Purine metabolism and autism

Autism is replete with different areas of research and investigation. Trends in the various lines of inquiry taken down the years have tended to coincide with the various scientific 'fashions' of the times. Outside of the more psychological themes, there was in the early days up to the mid-1990's, research which seemed to be very heavily biochemistry-focused in autism. Serotonin, dopamine, endorphins and enkephalins and other like-minded compounds took centre stage in the era of biological psychiatry. The brain (and its chemical minions) was King.

Then began the era of genetics which jumped with a loud 'ta-da' onto the autism research stage. The initial mapping of the human genome was the impetus and all and everything was about genes. It initially started with the various population-wide studies of genes, moving in later years to the realisation that autism, like many conditions, is not a 'single gene condition'. Increased interest in the various descriptions of the broader autism phenotype, together with advancing technology, heralded the age of SNPs and CNVs into autism research. Genes were King.

At the current time, I think we are evolving again; currently being in the process of another shift in the research paradigm, with the onset of epigenetics and gene-environment interactions. 'We are all a consequence of our genes and environment' - or so the fashion tells. Certainly the conclusions from many studies seem to be heading in that direction. The brain, genes and environment all sit on the same throne.

For this post I am venturing back a few years to those olden' days of biochemistry and autism, and in particular, research on purine metabolism in relation to autism. Mary Coleman was a main player in purine research in autism. She was no stranger to autism research by any means and credited with some very interesting (and early) observations including the suggestion that about a quarter of people with autism also presented with a co-morbid defined medical disorder.

To the post at hand. What are purines? Stand-by for biochemistry 101. There is quite a complex description of purines here. Basically purines are a class of compound which all share two particular details in their chemical structure called a pyrimidine ring and imidazole ring. Pyrimidines and purines are of some interest to geneticists generally because the nucleotides which form our DNA [(A)denine, (G)uanine, (C)ytosine, (T)hymine] are pyrimidines (C & T) and purines (A & G). Aside from forming the base nucleotides, purines have quite a few other roles to play body-wide, notably in relation to things like ATP as a main energy source for cells.

Purines have been of some interest to autism for a while. The connection between purines and autism seems to have been predominantly due to the excessive excretion of a particular purine, uric acid, reported by some authors (including Coleman). Many people might have heard about uric acid in relation to conditions such as gout (one of the 'many' diseases suggested to be carried by King 'Enry VIII) but there are quite a few other conditions potentially connected to elevated levels of uric acid. Coleman and colleagues estimated that about 20% of people with autism might present with elevated uric acid levels (hyperuricosuria) although whether this is co-morbidity or specifically tied into presented symptoms is unclear. There is a case report by Ted Page (who worked with Coleman) suggesting that treatment with uridine correlated with positive changes to presented autistic symptoms, with regression when treatment was halted. This was followed up by a small trial (n=9) where benefits were noted up to 8 years later. Interestingly, uridine is found in quite a few foods including brewer's yeast (saccharomyces cerevisiae) - a cousin (but not the same as) of our old friend saccharomyces boulardii.

As per my previous disclaimers, I am not suggesting that uridine or brewer's yeast in this context is in any way, shape or form an 'intervention' option for autism or anything else. The Page papers, whilst interesting, reported on only small participant numbers and as far as I can see no-one has yet done anything further on this issue to decide whether raised uric acid levels are a chance finding or if not just epiphenomenal. It is therefore difficult to ascertain proper safety or efficacy data in this area; an area which seems to have gone the same way as the sulphate (sulfate) research.