Saturday, 24 January 2015

Hartnup disease in coeliac disease: lessons for 'some' autism?

The paper by Thomas Ciecierega and colleagues [1] (open-access) talking about 'refractory' coeliac disease (CD) - a lack of, or diminished response to a gluten-free diet (the primary management option for CD) - and the subsequent diagnosis of Hartnup disease in a young girl is fodder for today's brief post.
I already had a big bowl of curly-toed weirdo for breakfast.

Describing how authors first diagnosed her with CD but witnessed "only mild clinical and laboratory improvement" following a regime of implementing a gluten-free diet and supplementation with various other nutrients via Total Parenteral Nutrition among other things, further examinations led to a suspicion of a niacin deficiency. The quite remarkable turn-around in clinical fortunes witnessed following the use of "oral niacin (50 mg three times daily)" led to the final diagnosis of Hartnup disease. This was confirmed by some bog-standard chromatography of a urine specimen which "showed increased levels of excreted neutral amino acids (glutamine, valine, phenylalanine, leucine, asparagine, citrulline, isoleucine, threonine, alanine, serine, histidine, tyrosine, tryptophan)." The authors conclude: "Co-occurrence of Hartnup disease and CD is extremely rare." I'd be minded to say, rare yes, but not unheard of in the peer-reviewed domain [2].

This case report stuck out to me for a few reasons. Coeliac disease and the broader spectrum of non-coeliac gluten sensitivity (NCGS) or non-coeliac wheat sensitivity if you wish, are quite a regular feature on this blog; even more so with the news that rates of CD are increasing [3]. Treatment of said 'gluten spectrum conditions' involves the use of a diet devoid of gluten which is found in various cereal products. Said diet also seemingly overlapping with other areas/conditions outside of CD including autism (see here). This is not however, the first time that a gluten-free diet has been talked about as not cutting the mustard in cases of something that initially looked like typical CD (see here).

Hartnup disease is something I came across quite early on in my autism research career. One of the compounds that I had some interest in called trans-indolyl-acryloylglycine (IAG) (see here) was thought to be derived from that ever so versatile aromatic amino acid called tryptophan. Whilst IAG turned out not to be the 'autism biomarker' that we initially thought it might be, one of the other clinical occasions that this compound cropped up in was, yes you guessed it, Hartnup disease. Hartnup disease and tryptophan have an interesting association [4].

Although not wishing to make connections where none may exist, the presentation of Hartnup disease might also manifest in behaviour as well as the more typical skin symptoms which can present [5]. I stumbled across an interesting BBC news article on the condition that mentions Hartnup disease in the same breath as 'the symptoms of autism' which, although rare, is something I've often thought merits further research attention. I'm not necessarily saying that autism = refractory coeliac disease = Hartnup disease - don't be silly - but it strikes me that there may be more to see in connecting some individual cases based on some biological overlap...

So: Paolo Nutini with Candy.


[1] Ciecierega T. et al. Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease. BMC Pediatrics 2014, 14:311 .

[2] Coudray-Lucas C. et al. Association of celiac disease and Hartnup's disease? Value of the tryptophan loading test. Gastroenterol Clin Biol. 1986 Feb;10(2):187-8.

[3] Zingone F. et al. Socioeconomic variation in the incidence of childhood coeliac disease in the UK. Arch Dis Child. 2015. 22 Jan.

[4] Milovanović DD. A clinicobiochemical study of tryptophan and other plasma and urinary amino acids in the family with Hartnup disease. Adv Exp Med Biol. 2003;527:325-35.

[5] Patel AB. & Prabhu AS. Hartnup disease. Indian J Dermatol. 2008 Jan;53(1):31-2.

---------- Ciecierega, T., Dweikat, I., Awar, M., Shahrour, M., Libdeh, B., & Sultan, M. (2014). Severe persistent unremitting dermatitis, chronic diarrhea and hypoalbuminemia in a child; Hartnup disease in setting of celiac disease BMC Pediatrics, 14 (1) DOI: 10.1186/s12887-014-0311-6