Wednesday 8 March 2017

Blocking FRAAs and thyroid function in autism (continued)

Readers of this post are advised to check out a previous blogging occasion describing how 'FRAAs - folate receptor alpha autoantibodies - may correlate with reduced thyroid function in cases of autism' before heading into this entry on the recent paper published by Richard Frye and colleagues [1].

You're back already? OK, well just in case you didn't read that last entry (😉), it's worthwhile first noting that: "Folate receptor α (FRα) autoantibodies (FRAAs) are prevalent in autism spectrum disorder (ASD). They disrupt the transportation of folate across the blood-brain barrier by binding to the FRα. Children with ASD and FRAAs have been reported to respond well to treatment with a form of folate known as folinic acid, suggesting that they may be an important ASD subgroup to identify and treat." Those are author words not mine (as is the clinical intervention mention).

The 'thyroid' addition to their recent paper follows that previous paper by the authors [2] stating that: "blocking FRAAs are associated with reduced thyroid function and suggest that thyroid function should be examined in children with ASD who are positive for the blocking FRAAs."

This time around the authors examined "blocking and binding FRAAs and thyroid stimulating hormone (TSH), free T4 (FT4), total T3 (TT3), reverse T3 (rT3), thyroid releasing hormone (TRH) and other metabolites" in 87 children diagnosed with an ASD. Some of their cohort had more than one measure of FRAAs, TSH and FT4.

Results: "TSH, TT3 and rT3 were above the normal range in 7%, 33% and 51% of the participants and TRH was below the normal range in 13% of the participants." Further: "TSH concentration was positively and the FT4/TSH, TT3/TSH and rT3/TSH ratios were inversely related to blocking FRAA titers." The observation that levels of thyroid stimulating hormone (TSH) were positively correlated with blocking FRAA titers follows the same pattern as the previous findings reported by authors. Elevations in TSH normally imply that the 'thyroid is struggling' and potentially leaning towards hypothyroidism; the correlation with FRAA titers *could* imply that those blocking antibodies might be part and parcel of why the thyroid is struggling. Ergo: "This study suggests that thyroid dysfunction in ASD may be related to the blocking FRAA."

Accepting that 'FRAA autism' (if I can call it that) is not a universal label to be applied to the autism spectrum (see here) the combined results in this area (with and without the thyroid bit added on) make for interesting reading. Not only do they offer yet another strand to the saying 'an autism diagnosis is the starting not finishing point' when it comes to assessments, but the possible intervention angle also comes to the forefront (see here).

What else would I like to see in this area? Well, quite a bit more work on thyroid function and autism could be a good starting point, outside of the maternal thyroid function (autoimmunity) and offspring risk bit (see here). Given that also all those thyroid metabolites are reliant on iodine (the number referring to the number of iodine units chemically attached), there could be quite a bit more to see when it comes to iodine and [some] autism too (see here). Then another research question: what happens to thyroid function as and when something like folinic acid is used? Science already has some idea that folinic acid - under double-blind, placebo-controlled conditions - might be useful for aspects of some autism (see here). Could we learn from other studies looking at folinic acid where thyroid function has been mentioned? [3] I daresay we could...

To close, science is great. Especially when it talks about case reports like this...


[1] Frye RE. et al. Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder. J Neuroendocrinol. 2017 Feb 15.

[2] Frye RE. et al. Folate Receptor Alpha Autoantibodies Modulate Thyroid Function in Autism Spectrum Disorder. NAJ Med Sci. 2014; 7: 53-56.

[3] Blehaut H. et al. Effect of leucovorin (folinic acid) on the developmental quotient of children with Down's syndrome (trisomy 21) and influence of thyroid status. PLoS One. 2010 Jan 11;5(1):e8394.

---------- Frye RE, Wynne R, Rose S, Slattery J, Delhey L, Tippett M, Kahler SG, Bennuri SC, Melnyk S, Sequeira JM, & Quadros E (2017). Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor alpha autoimmune disorder. Journal of neuroendocrinology PMID: 28199771

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