23908
Chymotrypsin: Evidence of a Novel Pancreatic Insufficiency in Children with ASD?
Emerging research has suggested that some children with ASD appear to be at high risk for gastrointestinal concerns. It has also been noted that many children with ASD have diets that are highly self- selective, e.g., having a preference for carbohydrates. Although it remains unclear what the basis for GI disruption is, it may be the case that some children with ASD have insufficient levels of digestive enzymes needed to process some food types, e.g., protein. If a child has this deficiency, they cannot optimally digest a class of food (e.g., protein), their food avoidance may be related to unpleasant sequelae associated with its ingestion (e.g., under-digested meat feeling like “lead shot” in the stomach). The enzyme chymotrypsin digests protein into its component amino acids. Amino acids, especially essential amino acids, play a crucial role in the production of neurotransmitters (e.g., dopamine and serotonin), are regulators of gene expression, and form the building blocks for new proteins.
Objectives:
The objectives of this study were: 1) determine the prevalence of abnormal levels of the enzyme fecal chymotrypsin (FCT) in children with autism, and 2) to determine whether FCT levels are associated with severity of autistic symptomatology.
Methods:
Participants were 323 children between the ages of 3 and 8 years (261 boys; mean age: 5.8 yrs.) who met DSM-IV criteria for Autistic Disorder, as screened by the Social Communication Questionnaire (SCQ) and confirmed by Autism Diagnostic Interview-Revised (ADI-R) and clinical interview. FCT levels were assessed using photometric assay of stool samples (performed by Quest Diagnostics); FCT levels ≤ 12.6 U/g are considered abnormally/pathologically low. Severity of autistic symptomatology was assessed using the total score of the Social Communication Questionnaire (SCQ) and the ADI-R subscale scores.
Results:
Of the 323 children, 198 (61.3%) had abnormally low/pathological levels of FCT activity (<12.6 U/g; mean FCT level=7.34), while 38.7% had normal levels (>12.6 U/g; mean FCT level=18.92). Comparison of FCT level and autism symptom level (i.e., ADI-R subscale scores, SCQ total score) in all participants revealed no statistically significant associations between FCT level and severity of autistic symptoms. This finding suggests that lower FCT levels in children with autism are not associated with more severe autistic symptomatology.
Conclusions:
The presence of low FCT levels in a large subset of children with autism suggests that chymotrypsin deficiency may be a key feature in some children with ASD. This enzymatic deficiency may place these at higher risk for a suboptimal supply of amino acids, which may in turn possibly undermine their ability to produce neurotransmitters, regulate gene expression, and synthesize new proteins. These findings may inspire further research into the role of the pancreas and amino acid deficiency in autism, and in a broader sense, into the physiology and biochemistry of a subset of children with autism. It also provides rationale for investigating chymotrypsin replacement therapy in children with autism who exhibit FCT deficiency.