Low Endogenous Fecal Chymotrypsin: A Possible Biomarker for Autism?
Although there is no approved medication for the treatment of the core symptoms of autism, there may be a subset of children with autism who “self-medicate” by selecting a diet favoring carbohydrates and avoiding protein. These dietary restrictions can be quite marked, and have been hypothesized to be related to oral defensiveness and idiosyncratic behavior. However, it may be the case that at least for a subset of children with autism this self-imposed dietary restriction may reflect a learned association between protein intake and gastrointestinal distress caused by inability to properly digest protein. We hypothesize that this digestive impairment may reflect a lack of amino acids (e.g., chymotrypsin) that are necessary to digest protein—with undigested proteins becoming allergens that alter gut flora, which in turn may lead to gastrointestinal discomfort. This inability to break down protein into component amino acids may also undermine the synthesis of new proteins such as neurotransmitters, which in turn would ultimately affect cognitive and behavioral status.
The objective of this study was to ascertain whether or not children with autism have abnormally low levels of the enzyme chymotrypsin, a serine protease that cleaves essential amino acids, relative to neurotypical children.
Fecal chymotrypsin (FCT) can be reliably measured using fecal samples; a FCT level of <9.0 units/gram is considered abnormally low. Endogenous levels of FCT were compared in 25 children with autism (19 boys; mean CA= 6.5 years) and 31 neurotypical children (15 boys; mean CA= 7.0 years). Children in the autism group met DSM-IV criteria for Autistic Disorder (DSM-IV: 299.00), as screened using the CARS/Gilliam and confirmed using clinical interview. Children in the neurotypical group did not meet DSM-IV criteria for an ASD, as ascertained via clinical. Stool samples were either obtained during a clinic visit or were brought in by the parents, and were tested by Quest Laboratories.
All children in the autism group had abnormally low FCT (mean FCT=3.96 units/gram; range: 1.2 – 6.4). In contrast, no children in the neurotypical group had abnormally low levels of endogenous FCT (mean FCT =23.7 units/gram; range: 14-35). ANOVA procedures revealed that these group differences were highly significant, F(1,44)= 227.53, p< .0001. There were no significant effects of age or gender on FCT level. Most notably, given there was no overlap between the two groups in terms of FCT level.
The results of this initial investigation strongly suggest that there may be at least a subset of children with autism who have very low levels of FCT, in comparison with their typically-developing peers. If this discontinuity in FCT between the two groups is replicated in a larger cohort of children, it may be the case that fecal chymotrypsin (FCT) may have utility as a potential biomarker for at least a subset of children with autism, and that enzymatic replacement therapy to compensate for this low FCT level may be indicated in these children.