We have to consider how ASD is being diagnosed at the moment and efficacy of treatment options. The prevalence of autism widely known along with the difficulties of differentiating diagnosis stemming from the unknown origin of loosely connected collections of genetic disorders. Common physical identifiers of ASD are profound learning disabilities and mental retardation which differ on a case by case basis in relation to signal response intensity and observed symptoms. These heterogeneities in clinical manifestations make precise diagnoses very difficult. In absence of diagnosis strength treatment options provided render low probabilities of effectively remedying the disorder. With 1 in 88 children estimated to have ASD, steps towards improving diagnostic and treatment technologies are of great importance. Learn more from NHS Heroes
Steps towards more robust diagnosis are being taken in the field of genetics. Recently genetic analyses of ASD have identified specific disease-causing genetic alterations and have provided interesting insights on potential treatments. These analyses resulted in identifying greater heterogeneity than previously thought to have surrounded Autism. Specifically each family of the disorder is harboring a unique set of disease causing variants again highlighting the difficulty of clinicians accurately diagnosing and treating the disease. However by gaining the 88th child’s genetic information, these studies show great growth in possible personalized treatments that may be delivered effectively to that child.
The studies contribute 10% of the ASD risk of spontaneous mutations (de novo mutations) in genes to associations found with the fragile X protein, FMRP, reinforcing links between autism and synaptic plasticity. Intriguingly the frequency of de novo mutations is related to paternal age; older fathers have a higher risk of conceiving autistic child.
Additional studies have indicated that about 6% of ASD cases are due to new large scale changes in chromosomes that affect gene copy number (de novo CNVs ). About 5% of ASD cases are caused by complete disruption of gene function – 3% of which are distributed across various chromosomes and 2% are affecting predominantly boys since they occur on the X-chromosome, further illustrating the growth potential of accurate diagnostics through genetic analyses.
A more specific branch of genetic analysis: exome sequencing, an excerpt of desired genome sequence, shows that mutations in many neuronal genes can cause autism – such as mild mutations in genes which play important distinct roles in neuronal signalling or brain development: PEX7, SYNE1, VPS13B, PAH, POMGNT1. Knowledge of specific mutations found through exome sequencing can lead to identifying unique treatment to counter specific mutation(s) observed in affected child.
In a case study one ASD child has a milder defect in the AMT gene that affects metabolism of glycin – an important amino acid that regulates neuronal signaling. Patients with severe mutations in AMT typically have the disorder Glycin encelopathy or nonketotic hyperglycinemia (NKH) – excess in glycin in blood (Applegarth and Toone, 2004). Classical NKH is severe genetic disease that leads to death within first year of life due to progressive lethargy, hypotonia, and severe seizures (Hamosh and Johnston, 2001). Elevated levels of glycin in patients with mild AMT mutation lead to delays in expressive language, behavioral problems, and only small subset has seizures. Therefore, it is possible to find ways to reduce glycin levels through special diets or treatment that reduce glycin absorption from food to reverse the negative impacts of overproduction.
Also some common medications could be re-purposed for treating neuronal diseases. For example treatment of mice genetically engineered to mimic the Fragile X disorder with lovastatinalleviated the abnormal neuronal activity by correcting the protein synthesis, opening possibilities that one day some children might benefit from simple and proven medications.
Such studies are greatly increasing the rate of clinical adoption of research discoveries. Personalized genetic diagnostics of ASD is important to find correct and optimal treatment strategy for each child. Greater implementation of this technology will not only provide case specific treatment to affected child but also provide critical data for the growth of research related to this area.