Scurvy and autism yet again...

"Here, we report a case of pediatric scurvy in an 11-year-old autistic child with a restricted diet who presented with refusal to walk, fatigue, a purpuric rash, and gingival bleeding."

Yep, the topic is scurvy and autism surfaces again on this blog (see here and see here and see here for other blogging entries), and yet another case report [1] illustrating how a disease that should really have been banished at least a century ago very much remains a part of modern medicine in some circumstances.

In case you didn't already know, scurvy is a disease of nutrition. A chronic lack of vitamin C (ascorbic acid), pretty vital for the synthesis and upkeep of collagen for example, leads to a variety of symptoms including weakness, fatigue, joint pain and perhaps most famously, bleeding gums (gingival bleeding). Vitamin C is present in many fruits and vegetables or can even be delivered as a supplement. Indeed, some pretty famous people have extolled the virtues of regular vitamin C consumption (see here) albeit with varying degrees of successful results outside of scurvy prevention or treatment.

As I mentioned, scurvy appearing alongside autism is not a novel finding. Restricted feeding patterns exemplified by the inclusion of a small repertoire of foods seems to be THE primary risk factor when it comes to scurvy following a diagnosis of autism. As far as I am aware, once the hurdle of actually diagnosing scurvy has been overcome, treatment with vitamin C supplementation seems to be able to resolve many symptoms pretty quickly both inside and outside the context of autism.

What's more to do in this area? Well, as I've mentioned before, screening for scurvy should perhaps be a lot more commonplace following a diagnosis of autism. Given that restricted feeding patterns - not necessarily including any special diets that are put in place for clinical reasons - are pretty frequent in relation to autism, there's a big case for further examinations for scurvy to be more widespread. Minus any clinical or medical advice being given or intended, use of nutritional supplements in the context of restricted feeding habits and autism might also be a sensible option given potential issues outside of just those linked to vitamin C (see here). Obviously this requires some clinical input to ensure that the right dose and preparation is given, but given the quite painful effects of something like scurvy, the question is: why should a diagnosis of autism be a barrier to sound health and wellbeing?

And as I write, there is yet more [2] appearing on this topic, and yet again treatment with vitamin C led to "rapid improvement"...

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[1] Burhop J. et al. Do You C What I C: Emergency Department Evaluation and Diagnosis of Pediatric Scurvy in an Autistic Child With a Restricted Diet. Pediatr Emerg Care. 2018 Jan 23.

[2] Kinlin LM. et al. Scurvy as a mimicker of osteomyelitis in a child with autism spectrum disorder. International Journal of Infectious Diseases. 2018. Feb 6.

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Food neophobia and autistic traits (or at least AQ defined autistic traits)

I was rather interested in the findings reported by Lorenzo Stafford and colleagues [1] suggesting "a positive association between food neophobia and the magnitude of autistic traits." Food neophobia is a fear of eating new or unfamiliar foods, and is something that most parents will have encountered at some point in their child/children's lives. With autism in mind, this type of issue is seemingly not uncommon in amongst various other food-related symptoms that can also be present.

Looking at the "broader aspects of autistic traits" and specifically whether a non-autistic (not diagnosed with autism) population showed any connection between their scores on the Autism Spectrum Quotient (AQ) and their scores on the Food Neophobia Scale (FNS), authors set about their study. They also examined whether olfactory sensitivity - "an olfactory threshold test for a food related odour" - might also show an effect in any relationship.

As per the opening paragraph to this entry, authors reported something of a relationship between AQ scores and FNS scores. Importantly, olfactory sensitivity did not seem to link in with AQ scores, suggesting that the link with food neophobia was not necessarily because of enhanced food odour perception for example. At least in this cohort.

This is potentially important work. Bearing in mind the quite small participant group (N=50), the reliance on "student participants" (not always the most representative of groups) as a non-clinical group and the assumption that AQ is actually measuring just the traits of autism (see here), the findings carry some interest. If there is indeed a connection between autistic traits and food neophobia, one could quite sensibly ask whether intervention(s) to ameliorate or reduce certain autistic traits might have some important knock-on effects for aspects of problematic food-related behaviours in relation to autism. Y'know, similar to the idea offered by other independent studies suggesting for example, that anxiety in the context of autism might be influenced by core traits (such as RRBs [restricted and repetitive behaviours]) and the implications thereof. Further investigations are implied.

And for those who might not fully understand just what food-related issues can mean in the context of autism...

Music to close: Harder, Better, Faster, Stronger.

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[1] Stafford KD. et al. Autistic traits associated with food neophobia but not olfactory sensitivity. Appetite. 2017. June 3.

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"early medical events are associated with clinical ASD phenotypes"

The paper by Charlotte Willfors and colleagues [1] (open-access) provides some food for thought today and the observation that various individual and cumulative medical events - "early medical events likely to be caused by environmental factors" - may be important to at least some autism.

Researchers "scrutinized the early medical histories of a rare and informative sample of 13 MZ [monozygotic] twin pairs discordant for clinical ASD [autism spectrum disorder]" also including "13 MZ typically developing (TD) control pairs (n=52) matched for sex" as an 'exploratory step. Discordant for autism means that one twin had autism and the other did not.

This research first step looked at medical events (likely to be caused by environmental factors!) included things like delivery and neonatal variables (e.g. foetal distress, hypoxia), minor and frequent infections (e.g. ear infections), allergy and epilepsy to name a few. Data was acquired from a few sources including medical records and medical history "assessed from a parent reported questionnaire." They examined exposure to the medical events "in relation to either quantitative or qualitative discordance for ASD." Qualitative discordance referred to when "only one twin within a pair meeting the diagnostic criteria of ASD." A 'confirmatory' study was also carried out whereby a larger, independent cohort of 100 twin pairs "quantitatively discordant for autistic traits" were also quizzed and findings cross-validated.

Results: a few non-shared environmental (NSE) events seemed to be important based on their analysis. So: "Single early medical factors, likely to be caused by NSE, that discriminated between twins in qualitative ASD discordant pairs were dysregulation during the first year of life (comprising feeding and sleeping problems, excessive crying and worrying) and birth weight." Authors also reported that cumulatively, the appearance of early medical events were significantly different in MZ twins with autism compared with their non-ASD co-twin. It's worth mentioning that some of those 'dysregulation' events have been talked about in the earliest descriptions of autism (see here). Birth weight too has something of a long-standing connection to [some] autism (see here). When it came to analysis based on autistic traits (the confirmatory study) it seemed that "early dysregulation and the cumulative load of a variety of early adverse medical events" continued to be important variables (although birth weight linked to ASD traits lost its significance).

These are important findings. The focus on MZ twins (who share a common structural genetic blueprint) means that the genetics side of things is to a large extent 'controlled for' and the results are more likely to reflect some environmental or, more accurately, non-genetic influence. There is a caveat to this though, as per the authors recognition: "with the exception of putative post-twinning de novo mutations." I might also add that MZ twins are also not necessarily epigenetically the same too so gene expression can (and does) differ. What causes these epigenetic differences is still the source of some debate but I might chime in with one idea (see here) out of many possibilities.

"Our data indicate that taking into account the cumulative load of early medical factors might strengthen or discourage a suspicion of ASD, at least in a minority of cases." This is an interesting thought provided by the authors based on their findings. It ties in well with the idea that although behavioural presentation is core to autism presentation and diagnosis, behaviour might not be the only important feature present in relation to autism. I do have to express a degree of caution however with such an approach based on the idea that various types of regression have been noted in the peer-reviewed literature to accompany some autism (see here) and with it, the concept of 'acquired autism' should really be properly recognised (see here for example) in these days of the plural 'autisms'. Indeed, there's a research study idea for anyone out there: looking at MZ twins discordant for autism with onset of said autism tied into a regression of skills?

Scientific replication is the name of the [future] game in this area of study, drawing on larger cohorts and perhaps based in other geographical areas outside of Sweden. We also need to find out what mechanisms might be potentially associating something like 'early dysregulation' with the onset of autism, taking into account how factors such as early feeding practices/issues for example, might provide at least one avenue for future study (see here).

To close, in light of some recent media headlines about the 'myth' that autism rates are on the up (and quite significantly so over past two decades), I offer some past posts suggesting that the word 'myth' should be reserved for other [non-peer-reviewed] matters (see here and see here and see here) and not this particular branch of epidemiological science. As to what may be 'causing' the upswing in numbers of diagnosed cases, well, it's likely to be very, very, very complicated (and without any need for sweeping generalisations please)...

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[1] Willfors C. et al. Medical history of discordant twins and environmental etiologies of autism. Transl Psychiatry. 2017 Jan 31;7(1):e1014.

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Willfors C, Carlsson T, Anderlid BM, Nordgren A, Kostrzewa E, Berggren S, Ronald A, Kuja-Halkola R, Tammimies K, & Bölte S (2017). Medical history of discordant twins and environmental etiologies of autism. Translational psychiatry, 7 (1) PMID: 28140403

Eosinophilic esophagitis (EoE): another over-represented condition in autism

Returning to the idea that not every symptom/characteristic present in cases of autism is necessarily 'due to autism' are the findings reported by Heifert and colleagues [1] and the observations that: "Children with ASD are more likely to be diagnosed with EoE [Eosinophilic esophagitis] compared to controls" and further: "A diagnosis of feeding disorder was strongly associated with EoE."

EoE is something that has been discussed before on this blog in relation to the myriad of gastrointestinal (GI) findings that have been reported alongside a diagnosis of autism (see here). Describing an inflammatory state affecting the esophagus (the tube that leads from mouth to stomach), there is still some debate about the exact hows and whys of the condition. As per the name, eosinophils (cells of the immune system) do seem to be involved in pathology of the condition but are likely to be only part of the clinical story. The primary overt symptoms of EoE tend to be based around feeding issues (dysphagia, regurgitation/vomiting and decreased appetite).

Heifert et al relied on data from the (US) Military Health System database capturing medical data on some 45,000 children diagnosed with an autism spectrum disorder (ASD) "from Oct 2008 to Sept 2013." Seeking to "evaluate the association of ASD with EoE", they compared records of participants with autism with over 225,000 age- and gender-matched controls and found that, whilst relatively small in frequency, EoE was more commonly reported in children with autism than in controls (0.4% vs. 0.1% respectively). Authors also reported that feeding disorders were associated with EoE in both kids with autism and those asymptomatic (not-autism) controls. They concluded that: "Feeding disorders in children with ASD should not be assumed to be solely behavioral and an esophagogastroduodenoscopy should be performed to evaluate for EoE."

This is important work. Feeding issues associated with autism are not uncommon. Although various explanations have been put forward down the years about how the symptoms of autism might exacerbate such issues, there is a growing realisation that other clinical diagnoses might also impact on their presentation too and should be screened for. The Heifert data is pretty strong data insofar as the participant numbers included and also the coding and structure of diagnoses like autism and EoE in the database used. Further research is indicated to substantiate the prevalence of EoE in cases of autism and whether, given the focus on immune function in manifestations of both conditions, there may be important overlaps. That treatment for EoE might include 'dietary elimination' linked into the idea that specific foods might trigger EoE also builds on the quite substantial research base looking at elements of diet and [some] autism (see here).

The bottom line: when a child (or adult) presents with feeding difficulties, don't just assume that 'it's just part of their autism'...

To close, today is about remembering; and perhaps reflecting on a poem: Dulce et Decorum est.

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[1] Heifert TA. et al. Feeding Disorders in Children with Autism Spectrum Disorders Are Associated with Eosinophilic Esophagitis. J Pediatr Gastroenterol Nutr. 2016 Jun 8.

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Heifert TA, Susi A, Hisle-Gorman E, Erdie-Lalena CR, Gorman G, Min SB, & Nylund CM (2016). Feeding Disorders in Children with Autism Spectrum Disorders Are Associated with Eosinophilic Esophagitis. Journal of pediatric gastroenterology and nutrition PMID: 27276430

Eating difficulties in adolescents with CFS/ME

I tread quite carefully when discussing the paper by Sarah Harris and colleagues [1] (open-access available here) on the potential causes and effects of 'eating difficulties' when it comes to adolescent chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME).

Careful because (i) I don't want to confuse eating difficulties with eating disorder (they are not one and the same) and (ii) the suggestion that some of the young adults included for study "recognised how their eating difficulties were exacerbated and maintained by psychological factors of low mood and anxiety" could potentially play into the concept of 'psychosomatic', something that quite a few people are trying to move on from when it comes to ME/CFS. I count myself in the camp describing CFS/ME as a real organic disease (or spectrum of diseases) potentially manifesting in various physiological and [secondary] psychological ways (see here).

A few details first: 11 teens were included for study (aged between 13-17 years). All had a diagnosis of CFS/ME but I'm not exactly sure which of the numerous criteria around were used to make that diagnosis. They were all "drawn from a CFS/ME specialist hospital service providing regional support for assessment and treatment of over 300 children a year" so I am assuming that someone, somewhere had confirmed the diagnosis (somehow). Interviews were arranged around the topics of "the adolescents’ experience of eating; the factors they felt caused and exacerbate eating difficulties and what they believed were helpful strategies" and various primary themes were pulled out from the transcripts.

Results: some interesting issues emerged, not least that quite a few participants "perceived their eating difficulties were caused by abdominal symptoms." 'Abdominal symptoms' is quite a nebulous term but specifically issues like bloating, indigestion and stomach cramps/pain were frequently mentioned. Also: "Nausea prior to eating often caused the adolescents to perceive that eating would make it worse or induce vomiting." My first thoughts on reading about these symptoms was a previous post on some research suggesting that 'abdominal discomfort syndrome' might be part and parcel of a subgroup of those with ME/CFS (see here). That and a possible role for certain foods [2] (see here also)...

Next: "Seven adolescents noticed a change in smell or taste (or both)" potentially impacting on their eating behaviours. Alongside perceived changes in the sensation of food texture said to accompany the onset of their CFS/ME, this also seemed to tie into some of the eating difficulties described. As odd as it might sound, the sorts of changes being described by this small participant group with CFS/ME to me sounded very similar to what has been talked about with the autism spectrum in mind. Many (many) moons ago I published a small opinion piece on eating difficulties associated with autism [3] and well, let's just say some not dissimilar themes cropped up. I'm not saying CFS/ME is autism or vice-versa, but it does intrigue me about the possibility of overlap (see here).

When it came to the idea of 'intervention' for such eating difficulties, the Harris paper also includes some information. "Adolescents frequently excluded various dietary items such as diary, gluten and sugar, claiming these created greater digestive disturbances, although they had not been given a medical explanation for this." Having already mentioned the Rowe paper on cow's milk protein intolerance, I don't want to stick too long on this aspect of intervention. All I will say is that there is nothing in the peer-reviewed literature at present to say that a diagnosis of CFS/ME is protective against genetic/biological issues with certain foods... and that also includes dietary gluten for example (see here).

Insofar as the other techniques possibly helpful with the eating difficulties described in this group, the authors talk about distraction and relaxation strategies as being potentially useful and also the involvement of healthcare professionals such as dietitians to help overcome some of the difficulties experienced. These all sound pretty reasonable intervention options. Again, drawing on some of the autism research literature (again, with no wild claims of association being made) I wonder if there might be some 'connection' between those sensory issues previously described and other clinical aspects such as anxiety as part and parcel of abdominal manifestations for example (see here)?

If there is a bottom line from the Harris data it is that a diagnosis of CFS/ME is certainly not protective against eating difficulties when it comes to young adults. I would like to see this research built upon in future in various ways; first and perhaps foremost is the testing of those presenting with abdominal symptoms for various digestion and/or food-related conditions (i.e. coeliac disease and the rather 'shades of grey' borders of non-coeliac gluten sensitivity for example). I don't want to make connections when none might exist but I'd also be minded to suggest that those trillions of wee beasties that call our gut home (the gut microbiota) might also be a target for further inspection too (see here) in light of their potential connection to all-things gut related. The sensory aspects hinted at in the Harris data are also deserving of quite a bit more study too. Without blowing my own trumpet too much, sensory features accompanying 'overlapping fatigue syndromes' is something else I've also discussed in the peer-reviewed literature [4].

In short, don't dismiss eating difficulties and their potential correlates when it comes to CFS/ME...

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[1] Harris S. et al. A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clin Child Psychol Psychiatry. 2016 May 23. pii: 1359104516646813.

[2] Rowe PC. et al. Cow's Milk Protein Intolerance in Adolescents and Young Adults with Chronic Fatigue Syndrome. Acta Paediatr. 2016 May 13.

[3] Whiteley P. et al. Feeding patterns in autism. Autism. 2000; 4: 207-211.

[4] Whiteley P. et al. Correlates of Overlapping Fatigue Syndromes. Journal of Nutritional & Environmental Medicine. 2004; 14:

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Harris S, Gilbert M, Beasant L, Linney C, Broughton J, & Crawley E (2016). A qualitative investigation of eating difficulties in adolescents with chronic fatigue syndrome/myalgic encephalomyelitis. Clinical child psychology and psychiatry PMID: 27215228

More extremes of a limiting diet and autism

In a previous post a while back, I discussed some examples in the peer-reviewed literature of where a self-limiting diet in the extreme can lead to with autism in mind. Today, I'm adding a further example of what food faddism might mean, to further forward the point that "a low threshold for vitamin level testing should be undertaken in autistic spectrum disorder cases, highlighting the importance of enquiring about dietary habits."

That last quote comes from the paper in question by Emma Duignan and colleagues [1] (open-access available here) who describe two case reports of teenagers with autism "with a background of moderate autistic spectrum disorder who were diagnosed with a multivitamin deficiency, including vitamin A." Said nutritional deficiency manifested as ophthalmic issues - relating to the physiology of the eye - that importantly seemed to abate following vitamin supplementation.

Aside from the idea that several factors might align to bring a person diagnosed with autism to a deficiency state, I was interested in the Duignan results for a few other reasons. I've talked about vitamin and mineral deficiencies a few times on this blog; more generally as per the results from Jim Adams and colleagues back in 2011 (see here) following the publication of their double-blind, placebo-controlled trial of supplementation through to more specific issues with something like the vitamin-of-the-hour, vitamin D (see here) or even the scurvy-preventer that is vitamin C (see here). There is quite a bit of literature out there to suggest that particularly in cases where dietary issues are noted to accompany a diagnosis of autism or autism spectrum disorder (ASD), one perhaps should expect nutritional deficiencies to follow.

The other thing that struck me about the Duignan results was the focus on ophthalmic issues as manifestations of those vitamin deficiency issues. It's not new news that among the various effects linked to something like vitamin A deficiency for example, vision and eye health may suffer. Although still in need of quite a bit of research, issues related to the eyes and knock-on effects for things like visual perception are no stranger to autism research as per my ramblings about the findings reported by Ikeda and colleagues [2]. The paper from Pineles and colleagues [3] on optic neuropathy due to vitamin B12 deficiency in cases of autism is also worth mentioning at this point and the question of whether at least some of the visual perceptual issues discussed with autism in mind might have a nutritional link?

We don't currently know how widespread nutritional deficiencies are when a diagnosis of autism is received because, at the moment, this is not something that is routinely tested for. On the basis of the Duignan and other results, I'd be minded to repeat my suggestion that where dietary issues are present for people on the autism spectrum, modern medicine could do a lot worse than find out whether there may be biological effects to come from a limited or restricted diet save any further charges of health inequality being levelled...

Music to close. Paul Simon - Me and Julio Down by the Schoolyard.

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[1] Duignan E. et al. Ophthalmic manifestations of vitamin a and d deficiency in two autistic teenagers: case reports and a review of the literature. Case Rep Ophthalmol. 2015 Jan 24;6(1):24-9.

[2] Ikeda J. et al. Brief report: incidence of ophthalmologic disorders in children with autism. J Autism Dev Disord. 2013 Jun;43(6):1447-51.

[3] Pineles SL. et al. Vitamin B12 optic neuropathy in autism. Pediatrics. 2010 Oct;126(4):e967-70.

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Duignan, E., Kenna, P., Watson, R., Fitzsimon, S., & Brosnahan, D. (2015). Ophthalmic Manifestations of Vitamin A and D Deficiency in Two Autistic Teenagers: Case Reports and a Review of the Literature Case Reports in Ophthalmology, 6 (1), 24-29 DOI: 10.1159/000373921

Extremes of a self-limiting diet in autism

I'll draw your attention to three papers in today's post which represent the extremes of where self-imposed dietary restrictions can potentially lead in relation to the autism spectrum disorders (ASDs). Issues with diet - outside of use of diet as an intervention measure - are something which have been talked about quite a bit in the autism research literature (see here).

"You look like a gangster"

The first paper by Baird & Ravindranath [1] describes a case report of an 11-year old with autism who became "critically ill" as a consequence of a diet exclusively limited to a single fast food, "a particular type of fried chicken". Liver dysfunction and "severe lactic acidosis" were listed as clinical findings ascribed to a diet "deficient in multiple micronutrients, including the B vitamins thiamine and pyridoxine". The authors reported some resolution of symptoms as and when B vitamin supplements were given including positive changes to "status epilepticus-with low serum pyridoxine- [which] resolved rapidly with pyridoxine". I might add that issues with lactate, elevated in lactic acidosis, are no stranger to autism research (see here and see here).

The second paper comes from Gulko and colleagues [2] and talks about "MRI findings of scurvy in four patients with autism or developmental delay". Scurvy, a condition characterised by a lack of vitamin C, is something which has cropped up before on this blog (see here) and as per the Gulko findings: "Despite its rarity, the radiologist must consider scurvy in a pediatric patient with a restricted diet presenting with arthralgia [joint pain] or myalgia [muscle pain]".

The final paper comes from Keown and colleagues [3] and describes the experiences of a young boy "identified to have a restricted diet" characterised among other things by consumption of "excessive quantities of carrot juice". As a result: "Blood investigations showed a raised serum carotene level and vitamin D deficiency". Vitamin D is something of an emerging area in relation to autism (see here).

Combined, these papers suggest yet another set of physiological variables which may require further clinical scrutiny as and when a child or adult presents with an ASD particularly where diet is mentioned as potentially being an accompanying issue. As per the findings from Marshall and colleagues [4], finding appropriate strategies to increase food variety (and not just food volume) remains an area in some need of further research.

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[1] Baird JS. & Ravindranath TM. Vitamin B Deficiencies in a Critically Ill Autistic Child With a Restricted Diet. Nutr Clin Pract. 2014 Aug 11. pii: 0884533614541483.

[2] Gulko E. et al. MRI findings in pediatric patients with scurvy. Skeletal Radiol. 2014 Aug 12.

[3] Keown K. et al. Nutritional implications of selective eating in a child with autism spectrum disorder. BMJ Case Rep. 2014 Mar 20;2014. pii: bcr2013202581.

[4] Marshall J. et al. Efficacy of interventions to improve feeding difficulties in children with autism spectrum disorders: a systematic review and meta-analysis. Child Care Health Dev. 2014 Jun 25.

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Baird JS, & Ravindranath TM (2014). Vitamin B Deficiencies in a Critically Ill Autistic Child With a Restricted Diet. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition PMID: 25112945



Gulko E, Collins LK, Murphy RC, Thornhill BA, & Taragin BH (2014). MRI findings in pediatric patients with scurvy. Skeletal radiology PMID: 25109378




Keown K, Bothwell J, & Jain S (2014). Nutritional implications of selective eating in a child with autism spectrum disorder. BMJ case reports, 2014 PMID: 24654242

Scurvy, vitamin C and autism

I'd been thinking about writing this post on scurvy, vitamin C and autism for quite a while. The paper by Kitcharoensakkul and colleagues [1] really made the decision for me, following their discussions on three young children with walking difficulties who were eventually diagnosed with scurvy, one of whom was diagnosed with autism. The authors concluded: "These clinical manifestations and radiologic findings highlight the importance for rheumatologists to have a higher index of suspicion for scurvy in nonambulatory children". Nonambulatory by the way, means not able to walk about (independently). "Interestingly, all patients had concomitant vitamin D deficiency" was another important point made in the Kitcharoensakkul study which is something I'm always a little interested in on this blog (see here).

Limes... @ Fludkov @ Wikipedia 

Scurvy, as some people might already know, is a condition characterised by a lack of sufficient vitamin C (ascorbic acid). It can manifest in a variety of ways including fatigue, lack of appetite, irritability alongside various functional gastrointestinal (GI) symptoms. Gingival swelling or bleeding (the gums) is perhaps one of the best known [oral] signs of the disease. Nowadays it is quite a rare condition.

In other blog entries I've referred to myself as a Limey reflective of a slang phrase for someone from these hallowed Isles called Great Britain (Britain, Britain, Britain..), which seems to derive from the practice of giving lime juice to British sailors way back when, to prevent scurvy.

Suffice to say however that the Kitcharoensakkul paper is not the first time that scurvy has appeared alongside the word autism or words autism spectrum disorder (ASD) as I'll attempt to show you...

• Case studies describing scurvy concurrent to a diagnosis of autism can be found in the peer-reviewed research literature [2]. The description by Mawson [3] is typical although some symptoms reported in that particular case as being perhaps complicated by "treatment with indomethacin, which lowers vitamin C levels" is an important addition. I do think it is important to raise the point that some medicines can interfere with the availability of things like vitamins and minerals similar to such nutraceuticals affecting some medicines.
• Cole and colleagues [4] talked about the continued presence of scurvy "among susceptible populations" which includes "certain unique populations-particularly the elderly subjects, patients with neurodevelopmental disabilities or psychiatric illnesses, or others with unusual dietary habits" in their report on a "10-year-old autistic child". 'Unusual' dietary patterns are no stranger to autism [5] (open-access here) over and above any special dietary regimes being implemented (see here).
• Congidi and colleagues [6] described another case of scurvy in "an autistic child with food-avoidant behavior". They also described MRI findings for their patient. Indeed, this is something also described in the report by Tetsu and colleagues [7] who reported that the: "imaging findings of the thigh showed diffuse signal abnormality in the bone marrow, periosteum, and the femoral muscle". Further: "A biopsy specimen of the femur showed hematoma, proliferative fibroblasts, and few collagen fibers, which suggested a deficiency of vitamin C".
• Slightly outside of the issue of scurvy is the study presented by Dolske and colleagues [8] "exploring the effectiveness of ascorbic acid (8g/70kg/day) as a supplemental pharmacological treatment for autistic children in residential treatment". Although this was a small trial in terms of participant numbers, it was a "double-blind, placebo-controlled trial" lasting 30 weeks. The authors reported "a reduction in symptom severity associated with the ascorbic acid treatment" making specific mention of "sensory motor scores". Obviously I'm not making any recommendations about these findings (no medical or clinical advice given or intended) but do find them to be interesting and perhaps overlapping with other research where vitamin C supplementation has been included. So, think back to the Jim Adams trial data (see here) based on some older research [9]. As to the hows and whys, well, unlike the chatter about vitamin C therapy potentially impacting on Epstein-Barr antibodies no biological measure was used in the Dolske study so we are left speculating...

As you've probably realised, most of the research evidence surrounding the presence of scurvy in cases of autism is based on individual case reports. I can't for example, provide you with any population estimates of how prevalent scurvy might be in cases of autism because no-one has really looked at this issue with any great assiduity. I can point you in the direction of other work talking again about cases of scurvy appearing alongside schizophrenia for example [10] but will only say that a poor diet lacking in sources of vitamin C is as much to blame in those examples as it probably is where cases of autism are discussed.

Just before I go, there are a few other things to note about vitamin C and autism which may also be pertinent to other issues. I've talked about iron before on this blog and how there is some data suggesting issues with iron for some on the autism spectrum (although certainly not all). It's quite long been recognised that vitamin C also plays a role in the absorption of iron [11] particularly non-heme iron sources and a deficiency in vitamin C is probably not going to be conducive to 'optimal' function. Quite a while back I also talked about autism and oxalates (see here) but will say no more than re-iterating the study by Chai and colleagues [12] with the requirement for lots more investigation in this area.

To close, I was saddened to hear of the death of Prof. Paul Patterson this week, a real research pioneer who's studies on autism and schizophrenia were frequently discussed on this blog (see here and see here). One of his final research contributions was the very important study fronted by Elaine Hsiao supporting a "gut-microbiome-brain connection in a mouse model of ASD". My condolences go to his family and those who knew him.

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[1] Kitcharoensakkul M. et al. Scurvy revealed by difficulty walking: three cases in young children. J Clin Rheumatol. 2014 Jun;20(4):224-8.

[2] Monks G. et al. A case of scurvy in an autistic boy. J Drugs Dermatol. 2002 Jul;1(1):67-9.

[3] Mawson AR. Bone pain, growth failure, and skin rash after an upper respiratory illness in a boy with autism: possible association with altered retinoid metabolism. Clin Pediatr (Phila). 2009 Jan;48(1):21-5.

[4] Cole JA. et al. Scurvy in a 10-year-old boy. Pediatr Dermatol. 2011 Jul-Aug;28(4):444-6

[5] Bandini LG. et al. Food selectivity in children with autism spectrum disorders and typically developing children. J Pediatr. 2010 Aug;157(2):259-64.

[6] Gongidi P. et al. Scurvy in an autistic child: MRI findings. Pediatr Radiol. 2013 Oct;43(10):1396-9.

[7] Tetsu N. et al. curvy in a Child With Autism: Magnetic Resonance Imaging and Pathological Findings. Journal of Pediatric Hematology/Oncology. 2012; 34: 484-487.

[8] Dolske MC. et al. A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993 Sep;17(5):765-74.

[9] Adams JB. & Holloway C. Pilot study of a moderate dose multivitamin/mineral supplement for children with autistic spectrum disorder. J Altern Complement Med. 2004 Dec;10(6):1033-9.

[10] Dubé M. Scurvy in a man with schizophrenia. CMAJ. Aug 9, 2011; 183(11): E760.

[11] Hallberg L. et al. The role of vitamin C in iron absorption. Int J Vitam Nutr Res Suppl. 1989;30:103-8.

[12] Chai W. et al. Oxalate absorption and endogenous oxalate synthesis from ascorbate in calcium oxalate stone formers and non-stone formers. AJKD. 2004; 44: 1060-1069.

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Kitcharoensakkul M, Schulz CG, Kassel R, Khanna G, Liang S, Ngwube A, Baszis KW, Hunstad DA, & White AJ (2014). Scurvy revealed by difficulty walking: three cases in young children. Journal of clinical rheumatology : practical reports on rheumatic & musculoskeletal diseases, 20 (4), 224-8 PMID: 24847751

Bah Ram Ewe, sheep be true

Babe, the sheep-pig, the hero/heroine of the novel (and films) by Dick King-Smith is always a family favourite. Babe's sheep-herding abilities are based in part on the revelation that there is a secret code among sheep 'Bah Ram Ewe, sheep be true'. As a user of this code, Babe earns a perfect sheep-herding round at the sheepdog trials; to be congratulated by Farmer Hoggett "That'll do Pig. That'll do" and satirised by Peter Griffin, everyone's favourite Family Guy.

Why oh why is he talking about Babe and sheep I thought I heard you ask? The reason is a new piece of research which suggests that even lambs can be picky eaters, and when fed monotonous diets, lambs become more stressed than lambs fed a diverse diet which is also reflected in their physiology and open-field behaviour.

The paper is this one by Villalba and colleagues* published in the journal Physiology & Behaviour. I appreciate that this might be pushing the boundaries of what this blog was originally supposed to do but what this and other research suggests is that we might be able to learn something from our wool-bound friends. Stay with me on this.

I will at this point add that I am in no way suggesting any person, any group of people, or any condition is in anyway related to sheep or any other animal. Some people may have heard that 'All cats have Asperger Syndrome' but not from me.

Back to sheep. The Villalba study looked at 3 diets: (i) a monotonous yet suitably nutritious diet, (ii) a diverse diet changing at set periods with various combinations of foods, (iii) a diverse diet similar to group (ii) also including supplementary phytochemicals. The results. When shown a more diverse diet, the monotonous diet sheep group got more stressed than the other groups as demonstrated by increased plasma cortisol levels and changes to rectal temperature when exposed to the open field test. Stress can be a learned response.

Whilst making generalisations from sheep behaviour to human behaviour is fraught with difficulties, I do feel as though there could be something in such research as this. The implication is that early dietary restrictiveness as a 'norm' might invoke a heightened stress response when a greater number of foods is presented to a person. So when a toddler who eats only pizza and chips (link to BBC3 programme 'Fast food baby') is presented with vegetables or fruit not normally included in the diet, the refusal side of things might not just bring about a tantrum but also some learned physiological stress? The flipside to such observations is that reducing the physiological stress response might make for a more varied diet, as per the recent presentation at the BPS conference on carrot not stick to get children to eat new foods.

Studying mammals like sheep perhaps removes some of the various social and cultural 'baggage' which would accompany similar human research. That and the fact that most human volunteers probably would not like their rectal temperature taken for any kind of experimental study; at least not without some significant reward. I will perhaps return to our mammalian friends at later points in this blog and how, as models of humans, they may offer some special insights into our very human behaviours e.g. autistic mice**?

* Villalba JJ.et al. Relationships between early experience to dietary diversity, acceptance of novel flavors, and open field behavior in sheep. Physiology & Behaviour. August 2011.

** Penagarikano O. et al. Absence of CNTNAP2 leads to epilepsy, neuronal migration abnormalities, and core autism-related deficits. Cell. September 2011.

A new first for British obesity

A few papers here in the UK ran with a story about obesity and an interesting, if slightly disturbing finding related to levels in the UK. A summary of the story in the Daily Mail is shown here, with the news that a recent survey from the Department of Health found that 4 English boroughs now have levels of obesity exceeding 30% of the population of that area. Why is 30% an important figure? Well, because that was the nationwide average predicted for 2025-2030 not so long ago (although it might get even worse).

Unfortunately Gateshead here in the good 'ole North East of England comes joint top with Tamworth, followed by Swale and Medway. A link to the NHS Choices website provides some background on what is obesity and how it is measured but the simple definition is a body mass index (BMI) greater than 30. The data by the way, is derived from the Department of Health, Health Profiles data.

There are a couple of interesting points to take from this news. First is the break with the commonly-used North-South divide. For my non-UK readers, there has for many years been an assumption that various health, social and economic differences exists in the UK (mainland UK) based on your geographical position - the 'North-South divide'. So, the more traditionally industrial North classically associated with heavy industry, manufacturing, the Industrial Revolution and working men's clubs is viewed differently to the more affluent, service and finance industries directed South. The difference between regional areas is never more stark than in research like this recent article from Hacking and colleagues published in the BMJ which ran with the headlines about the widest mortality gap for 40 years. The current top 4 obesity figures suggest at least that being a 'Northerner' or a 'Southerner' does not seem to protect/enhance your chances of becoming obese given the demographic data, although does not rule out socio-economic factors as being somehow involved.

Second are the various explanations reported on to account for the figures. I was struck by the use of the term 'obesogenic environments' attributed to Prof. Danny Dorling of Sheffield University (hopefully not misquoted). By that he means, a large density of fast-food outlets and few open spaces for exercise and recreation. If one is to believe this explanation accounting for the survey results, one accepts that obesity is purely a disease of lifestyle, or indeed culture (where other evidence suggests that it might not be that simple). Having visited Gateshead several times during my residency in this part of England, I would perhaps question whether it has a greater obesogenic environment than other parts of England. Fast-food for example is everywhere and as for open spaces, well I wouldn't single out Gateshead as being any more 'built-up' than any other part of the country, having green spaces such as the People's park and for all those hours of shopping on foot because of the ahem, parking issues, Newcastle Upon Tyne only a bridge away. The current Mayor of Gateshead offers another explanation for the Gateshead results and obesity in general: deprivation. He is also quoted (hopefully again not misquoted) as saying "We're bringing healthy food into schools. The children are happy to do without chips but it's the parents who make the decisions about what they eat for tea". His words not mine ('chips' by the way is the English term for a fried potato or french fries); although there's nothing like a sweeping generalisation. Pity the poor fried chip introduced into English culture in the 1860s-1870s as part of our national dish (fish and chips), perhaps a little time before our current obesity problems.

The survey figures are indeed a cause for concern in terms of the potential health implications to those people who are overweight or obese. I however would perhaps question whether the simplistic explanations and soundbites afforded to the data do it justice. In the end, obesity like many things, is very much more complicated than we think.

BPS conference highlights

I am quite a faithful follower of the British Psychological Society (BPS) and their various efforts related to all things psychology in the UK. There is always some interesting tidbits in their monthly magazine 'The Psychologist' to catch the eye and Dr Christian Jarrett does a sterling job promoting psychological research on his blog BPS Research Digest seen at the foot of this blog. Don't get me wrong, I don't necessarily agree with everything psychological, including its various impact on autism down the years. But when it comes to thinks like Nudge theory, psychology plays its hand.

Today (7th September 2011) sees the start of the annual Developmental Psychology section conference coincidentally held here in the North-East of England. With it comes the inevitable press releases on what will be presented; amongst which are a few studies which caught my eye.

First is this work presented by Faye Powell from Loughborough University on the suggestion that family mealtimes might help children to become less fussy in their eating patterns. It has the obvious 'psychological' explanation attached to family social eating times with friendly 'mother-child' relationships trumping coercive pressure strategies. So carrot rather than stick works best apparently when getting children to eat new foods. I don't know why but whenever I see the words 'mother-child relationship' all I think about is Bowlby and attachment theory or baby ducks imprinting on mother ducks; the pinnacle of psychology speak.

The second presentation is by Dr Hayley Leonard and colleagues from Goldsmiths, University of London on poor motor development in early infancy for children at risk of developing an autism spectrum condition. Based on data from the British Autism Study of Infant Siblings (BASIS), her results suggest that both fine and gross motor skills were poorer in an at risk group as early as 7 months of age.

Both these studies are of interest to me and autism research. Powell's presentation whilst on more generic feeding patterns cuts to the heart of a big day-to-day issue for many children with autism (and their parents) in terms of feeding times and what a child will and will not eat. I'm not for one minute suggesting that all the various feeding problems associated with autism will be solved by eating together because they won't; eating problems occur for lots of different reasons in autism. The 'social' aspect to family mealtimes is though of some interest.

The Leonard presentation goes back to the first formal descriptions by Leo Kanner nearly 70 years ago now, and his astute observations of motor and movement problems observed in some of his patient group. Indeed even in the past few days, motor movements in autism have received research coverage. Assuming that the results are reliable and reproducible, they offer another potential non-invasive string to the bow of any would-be early detection system for the presence of an autism spectrum condition. It might also offer a few neural insights also.

Summarising birth risk factors for autism

Hot on the heels of the various evidence published last week on the rise and rise of variable gene-environment interactions in relation to autism aetiology, an entry on the Autism Speaks blog directed me to a study published in the Pediatrics today which takes an overview look at the collected data on birth factors in relation to risk of developing autism. The abstract to the paper can be found here.

Based on a meta-analysis of several studies looking at various perinatal and neonatal risk factors analysed in connection to autism, several issues are suggested to be potentially related by Gardener and colleagues, although like many things about autism, no one factor or pattern of factors seems to show a universal connection.

So, issues such as umbilical cord 'complications' (I assume this means things like knots and/or being wrapped around baby's head), low birth weight and small for dates are a few of the risks which seem to show some possible connection. Others which have already come up on this blog in one shape or form include: hyperbilirubinemia, neonatal anaemia, feeding difficulties, and being a summer birth. I note also a possible connection with blood or rhesus incompatibility which is something I perhaps will go into in a future entry. There were a few other conditions not found to be associated with any increased risk including head circumference and prematurity. I was a bit taken aback by prematurity not showing association when the data were joined. Having said that, studies like this one have perhaps indicated that such issues might be more related to any co-morbid cognitive problems attached to the autism diagnosis. The head circumference factor is something that is due to be discussed in a separate post in the coming weeks.

I don't want to jump on to any bandwagon with these findings because, as the authors note, they were often comparing oranges and apples with the array of research reviewed. I do however think that this paper provides some important data when starting to look at both 'risk' factors in developing autism and possibly mechanisms; building on what is known about some of the birth factors listed and the risk of other physical and behavioural developmental conditions outside of autism.

The nose knows

I always consider it a bit of bonus when PubMed lists a paper which is a bit out of left-field. Not that I am complaining when more "mainstream" science is also published. But every now and again something crops up leading to one of those 'mmm?' moments. The paper in question this time relates to the curious title of this post (which incidentally was a book I remember reading as a child, one of the few, I might add, myself not being a great reader of books in general): odor detection threshold, but not odor identification, is impaired in children with autism.

Why was I so drawn to this paper? Well, I can't say for sure. Maybe it was the connection to perception and the human senses, some of which I have blogged about previously in relation to autism (vision and hearing). Maybe it was the use of the unusual 'Sniffin Sticks' test. Maybe it was the focus on one of the more under-represented senses. I can't say.

The study and findings: a small-ish sized group with Asperger syndrome/high-functioning autism compared with age and gender matched non-AS controls.  The odor/odour detection threshold (the point at which a smell is smelled) using the Sniffin' Sticks method was different (higher) in the AS compared to control groups. The AS group were also better at smelling orange but worse at smelling cloves (no other significant differences in other smells were found). The same group have published in this area before and the other research in this area is equivocal.

Assuming that there is a biological explanation for the results, I do wonder if this might be a small part of the proposed social side of things relevant to autism. More and more the research seems to imply that the traditionally held beliefs on problems with social cues in autism for example are not being borne out by the research. Even eye movements in relation to attention in autism appear fairly typical.

Smell on the other hand is our hidden social moderator. Aside from providing us with quite a bit of information about the person or place or other thing we are presented with, smell is also tied into things like pheromones. I know that there is still some debate on 'the human sex scent' and whether we are so swayed by it. One however only needs to look at menstrual synchrony to see that there may still be something in it, even at a subconscious level.

One could also assume that issues with smell might also tie into problems with feeding behaviours given that the olfactory and gustational (taste) senses are inter-linked (as we all find out when we eat whilst having a cold). I do perhaps think it might be a step too far to say that the feeding problems described in autism are exclusively tied into a problem with smell, but you never know, it might be at least contributory.

I would be interested to see what other research comes out in this area in future.

Early infant feeding practices

Feeding babies, or more precisely, what to feed babies and young infants has been quite a long-running debate.
I don't think anyone would really argue with the fact that breast milk is nature's way of providing everything a young infant needs to grow in those tentative early days, weeks and months, packaged up at just the right temperature with no late-night sterilisation of bottles or teats required. Perfect also for the groggy husband who grumbles to himself as he patters downstairs at 3am to do his paternal preparation duties.
Whether or not new mums want to, or can use this 'natural' option is another matter entirely.
I approach this subject with caution being, as I am, the wrong gender to make such a choice. I do however follow quite closely the various guidelines and debates on 'breast vs. bottle' and 'when to start weaning' as a matter of professional interest. Not least because of the link between very early weaning and increased risk of coeliac disease. Not least also because of the possible link between early feeding issues and autism as described in my posts here and here.
In recent times the question of 'when to start weaning' has been the source of some debate. One of the main issues is the age at which infants should start eating solid food and the conflicting advice being offered in this area. Here in the UK the official guidance is very clear: recommending exclusively breast / bottle feeding (or combined) for the first 6 months of life and weaning on to solid foods thereafter. This advice is backed up by the World Health Organisation (WHO) no less.
That would be all well and good if a report from the European Union hadn't mixed things up a little by suggesting that for some children, earlier weaning (from about 4 months onwards) might be OK and possibly advantageous. Added to that an article appearing in BMJ questioning our 6-month rule and again suggesting that there may be a case for revising guidance (backed up by the British Dietetic Association, BDA).
A case perhaps of the head saying do one thing, and the arms and fingers perhaps wanting to do something else.
I have thought about this issue quite a bit. Working backwards from the notion that all babies are different; have different constitutions, raised under different environments, raised by different parents one could argue that the n=1 principle might apply. Thinking also to what happens when research and guidelines get too generalised to a population there may be perhaps some scope for taking on board some of the suggested revisions at least for some infants (although please do not base your decision on my analysis, speak to your physician and healthcare provider about this).
The idea also that there is a window of opportunity for developing tolerance to foods is also an interesting concept. Readers may know of my interest in all things diet and gut-related, and in particular, the concept of the hyperpermeable gut (leaky gut) in connection to lots of things. One of the most interesting parts of how gut hyperpermeability might tie into weaning patterns is trying to ascertain when the gut is 'unpermeable' enough to tolerate food without permeability potentially leading to allergy or intolerance. The infant gut is quite permeable on purpose because: (a) it is still maturing, and (b) it has to allow the passage and absorption of all those goodies in breast milk (and formula) into the CNS, some of which are quite large molecules. Gut hyperpermeability may also have a role to play in producing that lovely soporific effect that babies love following their milk from all those warming opioid peptides and how this may relate to neural growth.
I will be interested to see where this debate goes eventually and how it may (may not) influence guidance and practice.

Food, feeding and autism

It's Bacon Conoisseurs’ Week this week here in the UK. Er.. happy Bacon Conoisseurs’ Week. Enjoy your er... bacon.

I know that this is a bit of a flaky way to start a post on food but please bear with me. The main reason that I am taking a look at food and feeding in autism spectrum conditions now is because of one of my previous posts on Kanner's original descriptions of autism and the fact that 6 of his 11 patients presented with early feeding problems. This really got me thinking about food (not just early feeding problems) as an issue.

Also, last night I chanced upon a programme called Supersize vs Superskinny Kids on Channel 4 and quite frankly I was pretty shocked by what I saw - not Mary Whitehouse shocked - but taken aback by the scale of food and feeding problems amongst quite a lot of kids nowadays in general. It got me thinking and questioning (hence the blog name): what are the main feeding issues present in childhood in autism, and are they so different from what seems to be happening with many kids in general, in these modern times?

Many years ago my colleagues and I published the results of a small scale trial looking at food and feeding behaviour in autism. It was not the best study ever done (i.e. no control group) but certainly also, not the worst. We asked parents about their child's food intake and feeding patterns, noted them in qualitative fashion and came up with a few, quite interesting things.

We found out for example that the children with autism in our group tended to have quite a restrictive diet in terms of the range of foods eaten. Nothing really earth-shattering there, given that various patterns of 'restricted' behaviour are core to diagnosis so why should feeding also not be affected?

When asked about the types of food which were included in the 'core' diet, there was some variability in the response. Some kids only liked 'dry' foods (crispy, crunchy); others only like soft foods (mushy, wet). For some kids it would be very 'bland' foods; for others it would be very 'strong' foods (I remember one child who enjoyed drinking neat cordial fruit juice without the water). Food refusal was pretty common. In some extreme cases there were reports of new foods being met with retching and/or vomiting even just by sight or smell, before taste. Food packaging also seemed to be quite important to some children. What brand, box, tin or bottle the food came from dictated whether it would be eaten or not. Some parents told us that they had taken to 'hiding' new foods in 'desired' food packages with varying degrees of success.

Looking at the other literature on food and feeding issues in autism, it looks like our study seemed to have captured the main issues: problems with food selectivity, food sensitivity (with regards to the perception of food eaten, not allergy or related mechanism) and an effect from food packaging.

Aside from the functional issues highlighted, we turn also to the more pathological aspects of food problems - when a feeding issue turns into a clinical issue - an eating disorder. There is still some controversy about whether eating disorders can/are present in autism spectrum conditions to any greater degree than in the general population.  Allowing for the fact that there may be some similarity in the cognitive profiles in autism and anorexia for example, there is only limited research on the prevalence of eating disorder in autism. One potential factor is gender: autism is male-dominated; anorexia is female-dominated; another is the varying impact of social factors which are thought to influence eating disorders. At this point I should mention that I am not going to discuss issues such as weight, BMI and diet in this post - perhaps in another post, but not this one.

We turn then to the question of whether such feeding issues are exclusive to childhood autism. Answer: probably not. Feeding problems are present in lots of different conditions including learning disability. Studies of LD seems to indicate similar issues to those noted in autism - food refusal, food selectivity, etc. Where a physical 'disability' is present, such as a cleft palette, food difficulties are exacerbated.
In the general population also, feeding problems seem to be quite prevalent. I found some difficulty in ascertaining exactly how prevalent given that lots of different factors can affect feeding habits. But many authors seem to say yes, they are prevalent to varying degrees; moderated by many things including age.

What then can we surmise from all this?

Autism is associated with food and feeding issues - yes. Other conditions are also associated with food and feeding issues - yes. Lots of children in the general population are affected by food and feeding issues - yes. Whilst not trying to downplay the effects of feeding problems in childhood autism spectrum conditions, the take-home message is that parents of children with autism are not alone on this issue.