By Dr. Paul El-Fishawy
Researchers at Yale and the University of California San Diego have discovered a new, likely rare, recessively inherited form of classic autism with epilepsy. Simultaneous errors in the genetic code of both the maternally and paternally inherited copies of a single gene, BCKDK, cause the disorder. The protein created by BCKDK acts as a brake on the body’s degradation of 3 amino acids (the branched chain amino acids). These nutrients, present in dietary protein, cannot be synthesized by the body but must be ingested. In patients with this form of autism, blood levels of these amino acids are significantly lower than normal, despite normal levels of other amino acids and adequate nutrition. Mice with the same genetic abnormality have neurological deficits that can be ameliorated by supplementing their diet with branched chain amino acids. This suggests the possibility that patients with this specific, likely rare disorder could benefit from supplementation and that autism could be potentially be prevented in infants with this disease.
However, it is critical to note that so far cases of this disorder have only been found in only three, rare families in the Middle East where the parents are related as first cousins. To date, no cases of autism in out-bred families in the United States or other Western countries have been shown to be attributable to this genetic defect. Thus, the discovery should not lead to the immediate alteration of current practices of diagnosis and treatment of patients in countries like the United States where cousin marriages are uncommon. There is no evidence from this study that supplementing autistic patients without this specific disorder with branched chain amino acids would be of any benefit.
We do not know how low levels of branched chain amino acids are causing autism in the patients. The importance of the finding is that it reveals a new biological pathway and a new biological marker. The hope is that further scientific exploration of this pathway could lead to improved diagnosis and treatments not only for patients with this specific disorder but also for other autistic patients.
One hypothesis about how low branched chain amino acids could be causing autism in these patients is that they could be leading to altered levels of neurotransmitters in the brain. The branched chain amino acids and other amino acids that compete with them for entry from the blood into the brain are key building blocks for the neurotransmitters glutamate, GABA, dopamine, and serotonin.