Monday, 13 February 2012

High lactate levels reported in about 1 in 5 children with ASD

I'm quite conscious of the fact that my last post on aromatic amino acids and bacteria was quite technical and jargon-filled. I apologise to readers for this. I perhaps got a little bit carried away with an area close to my research heart. This post also deals with some complex issues; the difference being that this time I admit to being no expert on mitochondrialactate or any related metabolite in relation to autism or anything else. I will try and describe some of the research leading to the post announcement but please don't take my word as gospel.

The sentence making up the title of this post was contained as part of this paper published by Dhillon and colleagues* (full-text). The manuscript is of the review-type looking at the various research on a possible relationship between mitochondrial DNA (mtDNA) and autism spectrum conditions and the 1 in 5 figure comes from this paper by Oliveira and colleagues**.

I guess it might be useful to introduce some basic information about lactate. First, don't confuse lactate with lactose or lactase mentioned in a previous posts on issues with milk. Neither be put off by all the jargon coming up - 'keep calm and carry on' as they say. It all starts with an energy source; in this case glucose, and how energy is released/metabolised via a process called glycosis; that is the conversion of glucose to pyruvate. I use the word pyruvate (and lactate) to generally mean pyruvic acid (or lactic acid) bearing in mind the chemistry of acids and bases in physiological terms.

Pyruvate forms an essential part of the Krebs cycle which onward ties into the electron transport chain and adenosine-5'-triphosphate (ATP), the energy transporter. There is quite a good graphical description of this process here. Pyruvate is also the important compound when it comes to lactate as a result of the enzyme lactate dehydrogenase making the change between the compounds under conditions without oxygen.  There is also some involvement with the coenzyme NAD+ (and NADH) but I don't want to complicate things any further. Pyruvate also cropped up in a previous post as one of five potential serum biomarkers for schizophrenia. Suffice to say that alterations in the levels of lactate might potentially indicate some pretty important things going on.

It was perhaps this paper by Coleman and Blass*** which really started the ball rolling with regards to lactate in which they reported an overlap between a diagnosis of autism and lactic acidosis. Lactic acidosis (high lactate levels and low pH levels) can result as a consequence of many different reasons including exercise and even that most final of processes rigor mortis; much to do with an absence of oxygen. Mitochondrial dysfunction has been suggested to be one source of this lack of oxygen (or at least issues with the Kreb's cycle functioning) as per the oft-cited review article by Rossignol and Frye.

Mary Coleman was again in many respects ahead of the game with her lactic acidosis findings in relation to cases of autism. Nearly 20 years after, Pauline Filipek and colleagues looked again at the whole pyruvate-lactate relationship in their study looking at carnitine deficiency and mitochondrial dysfunction in relation to autism. To quote: "Results for pyruvate, lactate, ammonia and alanine... collectively present a consistent picture of mild mitochondrial dysfunction". Don't even get me started on related findings on the amino acid alanine.

Other studies have suggested similar elevations in lactate although not universally so. Al-Mosalem and colleagues reported an approximate 40% increase in levels of lactate in children diagnosed with autism compared to controls. A finding similarly reported by some of the author group under separate cover. Indeed with these and various other reports I might be inclined to suggest that chronic elevations in lactate levels together with some of its relations might very well be important to the biology of at least some people with autism. As to how lactate levels may or may not directly impinge on the presented behaviours of autism is still a point of speculation.

To finish, the Cardigans in celebration of Valentines Day with Lovefool. Please don't forget that special someone (noting that flowers bought from the nearest petrol station are not generally that romantic).

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* Dhillon S. et al. Genetics and mitochondrial abnormalities in autism spectrum disorders: a review. Current Genomics. 2011; 12: 322-332.

** Oliveira G. et al. Mitochondrial dysfunction in autism spectrum disorders: a population-based study. Developmental Medicine & Child Neurology. 2005; 47: 185-189

** Coleman M. & Blass JP. Autism and lactic acidosis. JADD. 1985;15: 1-8

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ResearchBlogging.org Oliveira, G., Diogo, L., Grazina, M., Garcia, P., Psych, A., Marques, C., Miguel, T., Borges, L., Vicente, A., & Oliveira, C. (2007). Mitochondrial dysfunction in autism spectrum disorders: a population-based study Developmental Medicine & Child Neurology, 47 (3), 185-189 DOI: 10.1111/j.1469-8749.2005.tb01113.x