Is coeliac disease an aetiological factor in paediatric nonsyndromic intellectual disability?

In answer to the question posed in the title of this post on whether coeliac disease (CD) might show some connection to intellectual (learning) disability, 'probably not' is the finding reported by Taner Sezer and colleagues [1].

Researchers initially looked at "serum levels of tissue transglutaminase antibody and total IgA" in over 230 children diagnosed with nonsyndromic intellectual disability compared with about the same number of asymptomatic controls. Nonsyndromic intellectual disability by the way, is "defined by the presence of intellectual disability as the sole clinical feature" according to other sources [2]. They reported that "3 patients in the nonsyndromic intellectual disability group (5.45%) and 1 in the control group (0.41%) had positive serum tissue transglutaminase antibody." But when it came to the diagnosis of CD only 1 patient who had nonsyndromic intellectual disability fulfilled the gold-standard criteria of "Duodenal biopsy confirmed celiac disease."

The authors conclude by saying that the: "screening test for celiac disease should not be necessary as a part of the management of mild and moderate nonsyndromic intellectual disability." But further: "cases of severe nonsyndromic intellectual disability could be examined for celiac disease."

These are important data but as you may imagine, I'm minded to suggest that there may be other issues that require further attention. First, and in keeping with a recurrent theme on this blog, CD has a hallowed place in the whole 'gluten affects health' arena as the archetypal gluten-linked autoimmune condition. In recent years however, we've been introduced to the concept of a wider spectrum of issues with gluten not necessarily CD and not necessarily other gluten-related ills such as wheat allergy: non-coeliac gluten sensitivity (NCGS). I know there are ums-and-ahs about how real NCGS is and what constitutes diagnostic criteria (see here) but I'm of the opinion that we need to look at this wider concept with much greater assiduity.

Second, and allied to the idea that CD might not be the be-all-and-end-all of gluten issues is the idea that the serology of CD but not the histology might show some connection to behaviour. I say this with the Ludvigsson paper in mind (see here) and what it might mean for autism, a label that shares quite a bit of overlap with learning disability (see here).

Finally, I do find it interesting that whilst Sezer et al suggest that population-wide screening for CD should not be carried out for nonsyndromic intellectual disability they do suggest that specific cases might warrant further investigation. Drawing on the data from research on Down's syndrome for example, manifesting intellectual disability and carrying something of quite an elevated risk of CD (see here), it is evident that there may in some cases be a heightened risk of CD or other gluten-related issues co-occurring within this population. If one also considers that a gluten-free diet (the primary tool to manage CD) might also show some effect on EEG findings (see here) bearing in mind the connection between EEG findings, epilepsy / seizure-type disorders and intellectual disability [3], it's also not beyond the realms of possibility that further relationships might be noted with continued investigations in this area.

Music: The Libertines - What A Waster.

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[1] Sezer T. et al. Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability? J Child Neurol. 2015 Jun 15. pii: 0883073815589759.

[2] Kaufman L. et al. The genetic basis of non-syndromic intellectual disability: a review. Journal of neurodevelopmental disorders. 2010;2(4):182-209.

[3] Robertson J. et al. Prevalence of epilepsy among people with intellectual disabilities: A systematic review. Seizure. 2015 Jul;29:46-62.

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Sezer T, Balcı O, Özçay F, Bayraktar N, & Alehan F (2015). Is Celiac Disease an Etiological Factor in Children with Nonsyndromic Intellectual Disability? Journal of child neurology PMID: 26078418