Dr. Grossi's Blog
Autism spectrum disorders are a genetically heterogeneous array of syndromes which have as their core impairment social interactions, abnormal development of the social brain. These syndromes have received increasing attention because of what appears to be an increasing incidence and high impact on families from an emotional as well as financial standpoint. All treatments including somatic ones have been ineffective in addressing the core pathology but have been somewhat effective in dealing with specific symptoms clusters.
The genetic underpinning has thus far been elusive but with newer technologies such as DNA microarrays (DNA chip) and exome sequencing ( a strategy to sequence the coding portions of the genome) that allow for detection of CNV (copy number variation in DNA which presents as an abnormal number of gene copies or portions of genes) and point mutations suggests that progress is likely at hand. Point mutations have been discovered supporting the statistical conclusion that increased paternal age is a risk factor.
In the October 2012 issue of Science, Novarino et.al. use exome sequencing in related families to discover an inborn metabolic error associated with epilepsy, autism, and intellectual disability. Their results suggest that the more serious autistic presentations offer the best chance to find a causative mutation. There is an overlap in the genetics of these severe autistic disorders and severe intellectual disability presentations.
Additional observations suggest that the same genotype can lead to a number of phenotypes (presentations) including autism, intellectual disability, schizophrenia, bipolar disorder, and epilepsy. There is a large number of genetic combinations present in any single patient which implies variability of genetic expression in those individuals who do not meet criteria for any disorder.
Novvarino et.al. identified a point mutation for the gene BCKDK which results in increased degradation of branched chained amino acids. This defect in mice can largely be reversed by feeding branched chained amino acids. This suggests that newborn screening for this error, which has not yet been developed, could lead to a straightforward treatment. It's only a hope now but should it be proven effective, it would be a very big development.