Autism Spectrum Disorders (ASD) include a complex neuro developmental condition characterized by abnormal social interaction, verbal and non-verbal communication . Limited scientific advances have been made regarding the causes of ASD, with general agreement that both genetic and environmental factors contribute to this disorder . ASD has been associated to metabolic dysfunction .
Changes in over 1,000 genes have been reported to be associated with ASD, but a large number of these associations have not been confirmed. Many common gene variations, most of which have not been identified, are thought to affect the risk of developing ASD, but not all people with the gene variation will be affected. Most of the gene variations have only a small effect, and variations in many genes can combine with environmental risk factors, such as parental age, birth complications, and others that have not been identified, to determine an individual’s risk of developing this complex condition. Non-genetic factors may contribute up to about 40 percent of ASD risk.
By contrast, in about 2 to 4 percent of people with ASD, rare gene mutations or chromosome abnormalities are thought to be the cause of the condition, often as a feature of syndromes that also involve additional signs and symptoms affecting various parts of the body. For example, mutations in the ADNP gene cause a disorder called ADNP syndrome. In addition to ASD and intellectual disability, this condition involves distinctive facial features and a wide variety of other signs and symptoms. Some of the other genes in which rare mutations are associated with ASD, often with other signs and symptoms, are ARID1B , CHD2, CHD8 , DYRK1A, SHANK3 and SYNGAP1. In most individuals with ASD caused by rare gene mutations, the mutations occur in only a single gene.
In our patient, it had CHD8 gene mutation, in spite different gene mutations had been discovered in Autism but none of them had different presentation or describe the severity of behavior changes in Autistic child and non-had addressed the use of ketogenic diet in this different type of mutations.
Beneficial effects of KGD in children with ASD symptoms have been reported in two independent studies [17,18]. The first study evaluated the role of KGD on 30 ASD children . The John Radcliffe diet (a modified medium-chain triglyceride diet with a caloric distribution of 30% in medium-chain triglyceride oil, 30% fresh cream, 11% saturated fat, 19% carbohydrates, and 10% proteins) was administered for 6 months, with intervals of 4 weeks interrupted by two diet-free weeks. Of the 30 children, 40% did not comply or did not tolerate the diet. From the rest, the two children with the milder autistic behaviors showed the most improvement (as judged by total Childhood Autism Rating Scale score, concentration and learning abilities, and social behavior and interactions), while the rest displayed mild to moderate improvements. Interestingly, the beneficial effects of KGD persisted even after termination of the trial. Six of the children enrolled in this study had a higher baseline ketonemia with no apparent PDH and/or RC deficiencies; but it is not clear if any of the other patients underwent this screening, before and/or after the administration of the diet in addition to the lack of the inclusion of a control diet before administering the KGD to the ASD group or during the trial.
The other study  reports the administration of a gluten-free casein-free modified KGD (1.5:1 lipid : non-lipid ratio; medium-chain and polyunsaturated FA) for 14-months to a 12-year-old child with ASD and seizures with substantial medical comorbidities associated with a family history of metabolic and immune disturbances. Due to the improvements in seizure activity, improved electroencephalogram, cognitive and social skills, language function, and complete resolution of stereotypies, anticonvulsant medication doses were reduced without worsening of seizures. Of note, the administration of the diet was accompanied by a wealth of medications, a significant weight loss, and transitioning to puberty, so it is difficult to assess the sole role of the diet with this clinical background.
A ketogenic diet would extremely limit the sweet and starchy processed foods. This deprives certain gut bacteria of the food they need and may be a way to help restore balance in the microbiome. To further the argument of the role that the gut microbiota play on autism .
In mouse models of ASD Rett syndrome , and Succinate Semialdehyde Dehydrogenase (SSADH) deficiency , the use of the KGD has improved behavioral abnormalities (increased sociability and decreased self-directed repetitive behavior) and/or decreased the number of seizures, normalized ataxia, and increased lifespan of mutant mice. However, while the KGD was originally designed to be administered under controlled caloric intake. Most of the mouse studies have been performed under ad libitum conditions and/or for a relatively short period . Moreover, a ketogenic low-carbohydrate diet does not have a significant metabolic advantage over a non-ketogenic low-carbohydrate diet as judged by equal effects in body weight reduction and decreased insulin resistance; however, the former one was associated with higher inflammatory risk and increased perception of fatigue.
In a case study of a child with autism and epilepsy, following standard treatment non-response, the individual was placed on KD (1.5:1 lipid: non-lipid ratio) with adjunct anticonvulsant therapy . The patient was in ketosis. After initiation of the diet several benefits ensued including the resolution of morbid obesity and the improvement of cognitive and behavioural features of the disorder. After several years on the diet, the patient’s score on the Childhood Autism Rating Scale decreased from 49 to 17, a change from a rating of severe autism to non-autistic, and IQ increased by 70 points. Fourteen months following the initiation of the diet the patient was also seizure free.
Although the exact molecular mechanisms underlying the effect of the KGD are still under investigation, several scenarios are reported below to explore the potential therapeutic effects of the KGD in ASD.
Would the effect of ketogenic diet related to the different gene mutation that is associated with Autism not clear, this need more study and research.