Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency and autism?

I started this blogging year (2014) with a post talking about the need for further research consideration for a possible role of inborn errors of metabolism in relation to the presentation of at least some autism (see here). It is therefore timely that I (almost) end this year's blogging odyssey with reference to the paper by Amy Brown and colleagues [1] and their suggestion that although: "VLCAD deficiency does not have a significant impact on cognitive or motor skills" there may still be merit in looking further at very long chain acyl-CoA dehydrogenase (VLCAD) deficiency where: "Some children may be vulnerable to speech, social and behavioural issues."

Rule 42: All persons more than a mile high
must leave the court immediately

Although based on quite a small participant number (N=7), probably reflective of the fact that VLCAD deficiency is quite a rare disorder ("estimated at 1:30,000 in the US"), Brown and colleagues reported various findings based on the use of "a comprehensive neuropsychological assessment battery that assessed IQ, language, attention, memory, executive functioning, motor skills, behaviour, and social skills". Parents were also asked about their child's abilities in terms of things like social skills and behaviour.

Quite a few of the parameters investigated suggested that kids with VLCAD deficiency were average or above on their performance and presentation of skills. That being said: "Parents' questionnaires identified one child as having social skills deficits, and two as having behavioural problems such as hyperactivity. One child rated high on an autism spectrum subscale; another was formally diagnosed with autism spectrum disorder-both children were symptomatic at birth." I can't specifically provide you with answers as to how and why VLCAD deficiency might link to autism/autistic traits, but will provide you with a link to a previous paper [2] talking about long chain acyl-CoA dehydrogenase (LCAD) deficiency with a case report of autism in mind. LCAD and VLCAD have some interesting history. In that case, acyl-carnitines were discussed as potentially being relevant, which may very well tie into some other work in this area (see here). The fact also that carnitine is used as part of the treatment regime for some VLCAD deficiency might also overlap with other autism research (see here).

The two children talked about with autism in mind, one diagnosed with an autism spectrum disorder (ASD) and the other with some indication of autistic-like traits, hint at how some of the inborn errors of metabolism may yet provide some interesting insight into at least some autism. The paper by Burrage and colleagues [3] for example, updating on the field of branched-chain amino acid (BCAA) metabolism, offers further discussion on the possibility of a more generalised association as per the rise and rise of 'BCKDK autism'.

Bearing in mind our growing realisation of the plurality of autism - 'the autisms' - denoting not just the heterogeneity covered under the umbrella clinical description but also that more than one road might lead to the presentation of autistic traits, examining the inborn errors of metabolism with autism in mind is an area of great scientific potential. It benefits from some testable genetic/biological starting points with the detection of those inborn errors of metabolism which may provide some important insights into how [some] autism might come about. Given that some of those errors of metabolism can also be 'corrected' in various ways, it might also provide some pretty interesting data on how behavioural presentation might also be affected. Remember PKU? I'd like to see a lot more in this area.

A quick heads-up... tomorrow (30th December 2014) I'm gonna publish my annual round-up of some of the blogging highlights here on Questioning Answers in 2014. You're all invited to drop in and take a gander...

And then to some music: Elvis and Suspicious Mind.

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[1] Brown A. et al. Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening. Mol Genet Metab. 2014 Oct 12. pii: S1096-7192(14)00314-X.

[2] Clark-Taylor T. & Clark-Taylor BE. Is autism a disorder of fatty acid metabolism? Possible dysfunction of mitochondrial beta-oxidation by long chain acyl-CoA dehydrogenase. Med Hypotheses. 2004;62(6):970-5.

[3] Burrage LC. et al. Branched-chain amino acid metabolism: from rare Mendelian diseases to more common disorders. Hum Mol Genet. 2014 Sep 15;23(R1):R1-8.

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Brown A, Crowe L, Andresen BS, Anderson V, & Boneh A (2014). Neurodevelopmental profiles of children with very long chain acyl-CoA dehydrogenase deficiency diagnosed by newborn screening. Molecular genetics and metabolism PMID: 25456746