The Role of Protein Breakdown and Utilization In Children with Autism Spectrum Disorder

Background: Autism spectrum disorder (ASD) is a behavioral disorder with no definitive etiology. The various etiologies explored range from environmental to genetic, with no determinant. In some patients with ASD, primary GI immuno-pathology leads to secondary immune activation in the CNS that may contribute to the neurological features of autism, as well as a local inability for the gastrointestinal system to function properly thereby reducing function. This reduced function may also lead to various missing components of complete digestion, which may also affect the brain and brain function by limiting the pool of available amino acids.

Objectives: To determine if there is a statistical difference in the levels of fecal chymotrypsin between children with autism ages 24 months to 8 years and the same aged children who are neurotypical.

Methods: 463 children aged 24 months to 8 years of age; 266 diagnosed with autism and 197 neurotypical children were examined for levels of fecal chymotrypsin. The measurement was via enzymatic photospectroscopy method.

Results: Of the 266 children diagnosed with autism, 203 had abnormal levels of fecal chymotrypsin ( <8.4 U)  p<0.001. Of that group with abnormal levels, 129 of them have severely pathological low levels of chymotrypsin (<1.4U). Of the 197 neurotypical children, 3 tested below 8.4 U of chymotrypsin P<0.001.

Conclusions: These findings indicate that a subset of children with autism have an endogenous lack of chymotrypsin, a pancreatic enzyme, which cleaves only essential amino acids in the digestive process. The three major digestive proteases include trypsin, elastase and chymotrypsin. While elastase and trypsin cleave only one essential amino acid, chymotrypsin cleaves five essential amino acids including: tryptophan, tyrosine, phenylalanine, leucine, and methionine. Of note methionine serves as the initiation codon for all vertebrate proteins including those of the CNS and the PNS. Further it has been demonstrated that a lack of certain amino acids can turn on and off genes, specifically, methionine  is one of the amino acids, which is involved in turning on and off genes. Specifically a lack of methionine is involved in turning on the CHOP gene, which is involved in apoptosis of the cells of the CNS. The dearth of available amino acids and especially essential amino acids, potentially exists due to a lack of chymotrypsin, may leave the child with an amino acid prioritization problem, and potentially an inability to synthesize certain necessary proteins, including those such as neurotransmitters and neurotransmitter receptors. The abnormal levels of fecal chymotrypsin may leave the child with autism with a potentially devastating dearth of amino acids and especially essential amino acids from which to assimilate, utilize and synthesize new proteins. Thus the lack of chymotrypsin potentially leaves the child with digestive dysfunction as well as a neurological deficit