Autism and Learning Disabilities

Child with autism stacking cans. Courtesy Wikimedia.

What Is Autism and Learning Disabilities?

Autism and learning disabilities constititute a non-progressive psychiatric syndrome appearing in childhood characterized by withdrawal from communication with others often accompanied by repetitive or primitive behaviors.

Primary gastrointestinal pathology may play an important role in the inception and clinical expression of autism.

Autistic children often manifest complex biochemical and immunological abnormalities.1 Following are four  main features involving the digestive tract:

1) Brain dysfunction from an abnormal gut. Common characteristics of hepatic encephalopathy (brain dysfunction caused by liver disease) and a form of autism associated with developmental regression and immune caused gastrointestinal pathology (abnormal) in an apparently healthy child, have led to the proposal that there may be similar mechanisms of toxic brain dysfunction caused by gluten and casein proteins.

Gluten in wheat and casein in cow milk are called exomorphines because they act like morphine (opioid) in the brain. Aberrations in opioid biochemistry are common in autism.

2) Characteristic intestinal pathology. Many autistic children with gut symptoms have ileocolonoic lymphoid nodular hyperplasia and inflammation of the intestinal lining. The colon lesion consisting of a mucosal infiltrate of yo T cells and Celiac Disease8+ T cells and crypt cell proliferation is enhanced significantly, and the basement membrane is thicker than in normal or disease groups. Neutrophil and eosinophil mucosal infiltration and absence on colonic epithelium of HLA-DR antigen suggests a T-helper -2 dominated immune response.

The corresponding small intestinal lesion also shows a distinct inflammatory reaction in which immune-mediated epithelial cell damage is predominant and blood anitibodies of the IgG type colonizes with complement. 

3) Intestinal permeability abnormalities. A subset of children with autism were found to display increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with gastrointestinal symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.2

4) Secondary dysbiosis. Anaerobic dysbiosis develops in the colon caused by fermentation of the overload of undigested food arriving from the small intestine. Billions of microbes in the colon normally breakdown undigested food, however,  in autism, the process is dysfunctional and produces byproducts that are toxic to the brain resulting in encephalopathy.

What Is Autism and Learning Disabilities In Celiac Disease and/or Gluten Sensitivity?

• Relationship between autism and learning disabilities and celiac disease. Autism and learning disabilities are neurologic disorders associated with celiac disease and may be a presenting feature of untreated celiac disease in children whose immune system is abnormally triggered by gluten/casein proteins.3
• Relationship between autism and learning disabilities and gluten sensitivity. A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with gastrointestinal symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them. There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed.4
• Relationship between autism and learning disabilities and antibodies/intestinal permeability. In autistic children with paired/impaired intestinal permeability and under dietary regimen either regular or restricted found that the immune system of a subgroup of children with autistic spectrum disorders (ASDs) is triggered by gluten and casein. This could be related either to anti-gliadin IgG antibodies (AGA-IgG), deamidated-gliadin-peptide IgG (DGP-IgG), and Casein IgG elevated production or to impaired intestinal barrier function. Casein IgG titers resulted to be more frequently and significantly higher in ASDs than in controls. Intestinal permeability was increased in 25.6% of ASDs compared to 2.3% of healthy children. Systemic antibodies production was not influenced by paired/impaired intestinal permeability.3
• Relationship between autism and learning disabilities and diet. Some of the reported response to celiac diets in children with autism may be related to correction of nutritional deficiency resulting from undiagnosed gluten sensitivity and consequent malabsorption.5
• Relationship between autism and learning disabilities and abnormal stool pattern. By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%) and of rheumatoid arthritis (30% vs 11%). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%) than in those without. Additional studies are needed to examine a possible shared autoimmune process.6

How Prevalent Is Autism and Learning Disabilities?

Autism has increased prevalence in celiac disease.1

In 35 children with language regression, 24% vs 0% controls had an increased family history of celiac disease.6

What Are The Symptoms Of Autism and Learning Disabilities?

Autism is marked by these symptoms:

• Self-absorption.
• Inaccessibility.
• Aloneness.
• Inability to relate.
• Repetitive play.
• Rage reactions if interrupted.
• Rhythmical movements.
• Many language disturbances.
• Gastrointestinal symptoms include pain, esophageal reflux, diarrhea, chronic constipation.1

How Does Autism And Learning Disabilities Develop In Celiac Disease and/or Gluten Sensitivity?

• Autism results from an unclear mechanism.
• Gluten exposure with toxicity from the gut and autoimmunity are the forerunners. The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.7
• Lactic acidosis from acid tolerant bacterial overgrowth appear to contribute to development.

Does Autism and Learning Disabilities Respond To Gluten-Free Diet?

• A 24 month study showed that some patients with autism spectrum disorders improve on a gluten-free, casein-free diet.8
• AGA-IgG and DPG-IgG titers were higher in children with autistic spectrum disorders compared to controls and are only partially influenced by diet regimen.3
• Mainly post-natal (after the child is born) development of autism improves on gluten free diet and casein-free diet (cow’s milk).1
• Folic acid supplementation to achieve adequate levels is beneficial in fertile women. In a study sample of 85,176 children derived from the population-based, prospective Norwegian Mother and Child Cohort Study (MoBa), 270 children in the study sample had been diagnosed with autism spectrum disorders. Use of prenatal folic acid supplements around the time of conception was associated with a lower risk of autistic disorder in the MoBa cohort. Although these findings cannot establish causality, they do support prenatal folic acid supplementation,9

6 Steps To Improve Autism and Learning Disabilities In Celiac Disease and/or Gluten Sensitivity:

• 1Remove the Trigger. Maintain a Strict, Nutritious Gluten Free Diet:

• 2 Reduce Inflammation. Foods to Eat and Foods Not to Eat:

Because gluten is inflammatory, eliminate OTHER inflammatory foods from your diet to reduce an additive effect to gluten. At the same time, try to eat foods that reduce inflammation (anti-inflammatory).

• 3 Information Sheet You Can Take to Your Doctor or Other Health Professional:

Click here.

• 4 Manage Your Medications Safely:

• 5Nutritional Supplements To Help Correct Deficiencies:

• 6Manage Natural Remedies: 

What Do Medical Research Studies Tell About Autism And Learning Disabilities in Celiac Disease?

RESEARCH STUDY SUMMARIES

“Markers of Celiac Disease and Gluten Sensitivity in Children with Autism.” This study investigating immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease found that a subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with GI symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.

Study participants included 37 children (with or without gastrointestinal symptoms) diagnosed with autism according to both the AutismDiagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R), 27 of their unaffected siblings, and 76 age-matched healthy controls. Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles.

Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). The IgG levels were also higher compared to the unaffected siblings, but did not reach statistical significance. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them (p<0.01). There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed. A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with GI symptoms points to a potential mechanism involving immunologic and/or intestinal permeability abnormalities in affected children.12

“Antibodies against food antigens in patients with autistic spectrum disorders.” This study investigating the prevalence of antibodies to gliadin and milk proteins in autistic children with paired/impaired intestinal permeability and under dietary regimen either regular or restricted found that immune system of a subgroup of children with autistic spectrum disorders (ASDs) is triggered by gluten and casein. This could be related either to AGA, DPG, and Casein IgG elevated production or to impaired intestinal barrier function.

162 ASDs and 44 healthy children were investigated for intestinal permeability, tissue-transglutaminase (tTG), anti-endomysiumantibodies (EMA)-IgA, and total mucosal IgA to exclude celiac disease; HLA-DQ2/-DQ8 haplotypes; total systemic antibodies (IgA, IgG, and IgE); specific systemic antibodies: α-gliadin (AGA-IgA and IgG), deamidated-gliadin-peptide (DGP-IgA and IgG), total specific gliadin IgG (all fractions: α, β, γ, and ω), β-lactoglobulin IgG, α-lactalbumin IgG, casein IgG; and milk IgE, casein IgE, gluten IgE,-lactoglobulin IgE, and α-lactalbumin IgE.

AGA-IgG and DPG-IgG titers were higher in ASDs compared to controls and are only partially influenced by diet regimen. Casein IgG titers resulted to be more frequently and significantly higher in ASDs than in controls. Intestinal permeability was increased in 25.6% of ASDs compared to 2.3% of healthy children. Systemic antibodies production was not influenced by paired/impaired intestinal permeability.3

“The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders.” This study reports the results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive ‘catch-up’ design and interim analysis. Results suggest that intervention using a gluten free and casein free diet may positively affect developmental outcome for some children diagnosed with autism spectrum disorders (ASD).

Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomization. Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) were used to assess core autism behaviors, Vineland Adaptive Behavior Scales (VABS) to ascertain developmental level, and Attention-Deficit Hyperactivity Disorder – IV scale (ADHD-IV) to determine inattention and hyperactivity.

Participants were tested at baseline, 8, and 12 months. Based on per protocol repeated measures analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement to mean diet group scores (time*treatment interaction) on sub-domains of ADOS, GARS and ADHD-IV measures. Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment.

Stage 2 data for 18 group A and 17 group B participants were available at 24 months. Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention. In the absence of a placebo condition to the current investigation, we are, however, unable to disqualify potential effects derived from intervention outside of dietary changes. Further studies are required to ascertain potential best- and non-responders to intervention.13

“Association of family history of autoimmune diseases and autism spectrum disorders.” This nationwide study investigating the association between family history of autoimmune diseases (ADs) and autism spectrum disorders (ASDs)/infantile autism confirmed associations from previous studies regarding family history of type 1 diabetes and infantile autism and maternal history of rheumatoid arthritis and ASD. A significant association between maternal history of celiac disease and ASDs was observed for the first time.

The study cohort consisted of all of the children born in Denmark from 1993 through 2004 (689 196 children). A total of 3325 children were diagnosed with ASDs, of which 1089 had an infantile autism diagnosis. Outcome data consisted of both inpatient and outpatient diagnoses reported to the Danish National Psychiatric Registry. Information on ADs in parents and siblings of the cohort members was obtained from the Danish National Hospital Register. The incidence rate ratio of autism was estimated by using log-linear Poisson regression.

The observed associations between familial autoimmunity and ASDs/infantile autism are probably attributable to a combination of a common genetic background and a possible prenatal antibody exposure or alteration in fetal environment during pregnancy.7

“Gastrointestinal symptoms in children with an autism spectrum disorder and language regression.” This cross-sectional study comparing gastrointestinal problems in children with an autism spectrum disorder with and without a history of language regression found an association between children with language regression, a family history of autoimmune disease, and gastrointestinal symptoms. Structured interviews were conducted in 100 children with autism spectrum disorder.

By parental report, children with language regression more frequently exhibited an abnormal stool pattern (40% vs 12%) and had an increased family history of celiac disease or inflammatory bowel disease (24% vs 0%) and of rheumatoid arthritis (30% vs 11%). Among 35 children with a family history of autoimmune disease, an abnormal stool pattern was reported more frequently in those with language regression (78% vs 15%) than in those without. Additional studies are needed to examine a possible shared autoimmune process.14

CASE REPORT SUMMARIES

“Celiac disease presenting as autism.” This case report describes diagnosis of celiac disease in a 5-year-old boy diagnosed with severe autism at a specialty clinic for autistic spectrum disorders. After initial investigation suggested underlying celiac disease and varied nutrient deficiencies, a gluten-free diet was instituted along with dietary and supplemental measures to secure nutritional sufficiency. The patient’s gastrointestinal symptoms rapidly resolved, and signs and symptoms suggestive of autism progressively abated. This case is an example of a common malabsorption syndrome associated with central nervous system dysfunction and suggests that in some contexts, nutritional deficiency may be a determinant of developmental delay. It is recommended that all children with neurodevelopmental problems be assessed for nutritional deficiency and malabsorption syndromes.15

1. Wakefield AJ, Puleston M, Montgomery SM, Anthony A, O’Leary JJ, Murch SH. Review Article: the concept of entero-colonic encephalopathy, autism, and opioid receptor ligands. Aliment Parmacol Ther. 2002; 16:663-674. [↩] [↩] [↩] [↩]
2. Lau NM, Green PH, Taylor AK, Hellberg D, Ajamian M, Tan CZ, Kosofsky BE, Higgins JJ, Rajadhyaksha AM, Alaedini A. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism. PLoS One. 2013 Jun 18;8(6):e66155. Print 2013. [↩]
3. de Magistris L, Picardi A, Siniscalco D, Riccio MP, Sapone A, Cariello R, Abbadessa S, Medici N, Lammers KM, Schiraldi C, Iardino P, Marotta R, Tolone C,Fasano A, Pascotto A, Bravaccio C. Antibodies against food antigens in patients with autistic spectrum disorders. Biomed Res Int. 2013;2013:729349. doi: 10.1155/2013/729349. [↩] [↩] [↩] [↩]
4. Lau NM, Green PH, Taylor AK, Hellberg D, Ajamian M, Tan CZ, Kosofsky BE, Higgins JJ, Rajadhyaksha AM, Alaedini A. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism. PLoS One. 2013 Jun 18;8(6):e66155.. [↩]
5. Genuis SJ, Bouchard TP. Celiac disease presenting as autism. J Child Neurol. 2010 Jan;25(1):114-9. doi: 10.1177/0883073809336127. [↩]
6. Valicenti-McDermott MD, McVicar K, Cohen HJ, Wershil BK, Shinnar S. Gastrointestinal symptoms in children with an autism spectrum disorder and language regression. Pediatr Neurol. 2008 Dec;39(6):392-8. doi: 10.1016/j.pediatrneurol.2008.07.019. [↩] [↩]
7. Atladóttir HO1, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW, Parner ET. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics. 2009 Aug;124(2):687-94. doi: 10.1542/peds.2008-2445. [↩] [↩]
8. Whiteley P1, Haracopos D, Knivsberg AM, Reichelt KL, Parlar S, Jacobsen J, Seim A, Pedersen L, Schondel M, Shattock P. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010 Apr;13(2):87-100. doi: 10.1179/147683010X12611460763922. [↩]
9. Surén P, Roth C, Bresnahan M, Haugen M, Hornig M, Hirtz D, Lie KK, Lipkin WI, Magnus P, Reichborn-Kjennerud T, Schjølberg S, Davey Smith G, Øyen AS, Susser E, Stoltenberg C. Association between maternal use of folic acid supplements and risk of autism spectrum disorders in children. JAMA. 2013 Feb 13;309(6):570-7. doi: 10.1001/jama.2012.155925. [↩]
10. Cummins AG, Thompson FM, Butler RN, et al. Improvement in intestinal permeability precedes morphometric recovery of the small intestine in coeliac disease. Clinical Science. Apr 2001;100(4):379-86. [↩]
11. Farhadi A, Banan A, Fields J, Keshavarzian A. Intestinal barrier: an interface between health and disease. Journal of Gastroenterology and Hepatology. 2003;18:479-91. [↩] [↩] [↩] [↩] [↩] [↩]
12. Lau NM, Green PH, Taylor AK, Hellberg D, Ajamian M, Tan CZ, Kosofsky BE, Higgins JJ, Rajadhyaksha AM, Alaedini A. Markers of Celiac Disease and Gluten Sensitivity in Children with Autism. PLoS One. 2013 Jun 18;8(6):e66155. [↩]
13. Whiteley P, Haracopos D, Knivsberg AM, Reichelt KL, Parlar S, Jacobsen J, Seim A, Pedersen L, Schondel M, Shattock P. The ScanBrit randomised, controlled, single-blind study of a gluten- and casein-free dietary intervention for children with autism spectrum disorders. Nutr Neurosci. 2010 Apr;13(2):87-100. doi: 10.1179/147683010X12611460763922. [↩]
14. Valicenti-McDermott MD, McVicar K, Cohen HJ, Wershil BK, Shinnar S. Gastrointestinal symptoms in children with an autism spectrum disorder and language regression. Pediatr Neurol. 2008 Dec;39(6):392-8. doi: 10.1016/j.pediatrneurol.2008.07.019. [↩]
15. Genuis SJ, Bouchard TP. Celiac disease presenting as autism. J Child Neurol. 2010 Jan;25(1):114-9. doi: 10.1177/0883073809336127. [↩]