Decreased urinary creatinine levels associated with autism (again)

One finding in particular stood out from those reported by Lussu and colleagues [1] following some nifty metabolomic investigations: decreased levels of urinary creatinine in their cohort of participants diagnosed as on the autism spectrum (n=21) compared with "controls (n = 21), these being siblings of autistic patients."

Based on the "use of 1 H-NMR metabolomics to analyze the global biochemical signature of ASD [autism spectrum disorder] patients" researchers turned again to a favourite topic of this blog - metabolomics -  and how the detection and identification of small molecules in various biofluids (urine, blood, saliva, etc) might be particularly informative. Metabolomics is, in essence, all about two things: (i) the analytical technology used to analyse a sample and (ii) the statistical technology used to make sense of the chemical analysis. If one assumes that a biofluid like urine literally contains thousands of compounds and small molecules, you get a flavour for the task facing researchers in this area.

I've talked metabolomics a few times on this blog with autism in mind (see here and see here for examples) but have chosen to zoom in on the Lussu findings in relation to an interesting compound called creatinine. Creatinine is a break-down product of creatine phosphate typically found in muscle. It's generally used as a rough-and-ready guide to the dilution of a urine sample given that it is produced at quite constant rate (see here).

In my day job, I continue to have some interest when it comes to creatinine (urinary) in the context of autism as per some research published a decade or so back [2]. My colleagues and I reported: "Controlling for sample pH and body mass index [BMI], a significant decrease in urinary creatinine concentration was found in the PDD [pervasive developmental disorder] group compared to controls." Other [independent] researchers have also reported similar things [3] when it comes to blood levels of creatinine in the context of autism.

Unfortunately I don't yet have a good explanation as to why creatinine seems to be on the low side when it comes to at least some autism bearing in mind issues such as BMI can seemingly affect values. I do find in interesting that muscle mass may have a bearing on urinary creatinine excretion and could perhaps stretch an association with [some] autism on the basis of more generalised issues with muscle function or tone (see here). That low urinary creatinine *may* also point to issues with kidney function is also interesting and invites quite a bit more study on this organ in relation to autism...

Music: Acceptable in the 80's.

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[1] Lussu M. et al. The urinary 1 H-NMR metabolomics profile of an italian autistic children population and their unaffected siblings. Autism Res. 2017 Mar 11.

[2] Whiteley P. et al. Spot urinary creatinine excretion in pervasive developmental disorders. Pediatr Int. 2006 Jun;48(3):292-7.

[3] West PR. et al. Metabolomics as a tool for discovery of biomarkers of autism spectrum disorder in the blood plasma of children. PLoS One. 2014 Nov 7;9(11):e112445.

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Lussu M, Noto A, Masili A, Rinaldi AC, Dessì A, De Angelis M, De Giacomo A, Fanos V, Atzori L, & Francavilla R (2017). The urinary 1 H-NMR metabolomics profile of an italian autistic children population and their unaffected siblings. Autism research : official journal of the International Society for Autism Research PMID: 28296209

Low muscle tone and autistic traits

"This large study showed a prospective association of infant muscle tone with autistic traits in childhood."

So said the findings reported by Fadila Serdarevic and colleagues [1] who, looking at nearly 3000 children, were able to assess early motor development and muscle tone "between ages 2 and 5 months" and later parental ratings of autistic traits in children at 6 years of age. Said autistic traits were surveyed using the "the Social Responsiveness Scale (SRS) and the Pervasive Developmental Problems (PDP) subscale of the Child Behavior Checklist." Authors concluded that there was something of a connection between low muscle tone and autistic traits: "Low muscle tone in infancy predicted autistic traits measured by SRS... and PDP" and further: "early detection of low muscle tone might be a gateway to improve early diagnosis of ASD [autism spectrum disorder]."

Just before anyone gets ahead of themselves with this data, it is worth pointing out that despite the large participant group included for study and the prospective nature of the study design, this was a study only really looking at two sets of variables across quite a long time-frame. It's not beyond the realms of possibility that other factors might influence the presentation of [parent-reported] autistic traits outside of just early measures of muscle tone or anything related...

But let's set this research in some context. Muscle tone in a broader sense had been noted to be potentially 'linked' to autism in some of the earliest texts on the topic (see here). More recent discussions on how motor skill in the context of gait for example, might be something important to at least some autism (see here) add to the relevance. One might also look to the some of the typical reasons why low muscle tone (hypotonia) may present to see whether there are areas that could inform autism research too. I note for example, mention of Ehlers-Danlos syndrome (EDS) in some of the texts and this would perhaps appeal to further investigation on any overlap between EDS (or other connective tissues disorders) and autism (see here). Serious infections such as encephalitis and meningitis have also been mentioned in the context of hypotonia, and again, might be indicated in relation to hypotonia and some autism (see here). There is also a possibility that hypotonia could (in some cases) be tied into mitochondrial disease; something else that could be relevant to at least some 'types' of autism (see here). All of these areas are worthy of further research inspection added to the idea that muscle tone might be rather more core to autism than many people might appreciate.

'And the best picture goes to'...

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[1] Serdarevic F. et al. Infant muscle tone and childhood autistic traits: A longitudinal study in the general population. Autism Res. 2017 Feb 9.

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Serdarevic F, Ghassabian A, van Batenburg-Eddes T, White T, Blanken LM, Jaddoe VW, Verhulst FC, & Tiemeier H (2017). Infant muscle tone and childhood autistic traits: A longitudinal study in the general population. Autism research : official journal of the International Society for Autism Research PMID: 28181411