Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We herein report the joint occurrence of an autistic disorder (AD) and X-linked hypophosphatemia. X-linked hypophosphatemia (XLH), an X-linked dominant disorder, is the most common of the inherited renal phosphate wasting disorders. Autism is a pervasive developmental disorder that occurs mainly due to genetic causes. In approximately 6-15% of cases, the autistic phenotype is a part of a broader genetic condition called syndromic autism.Therefore, reports of cases with the joint occurrence of a known genetic syndrome and a diagnosis of ASD by a child psychiatrist are relevant. A joint occurrence does not, however, mean that there is always a causal link between the genetic syndrome and the autistic behavioural phenotype. In this case, there are a number of arguments countering a causal link.
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PMID:Autism and X-linked hypophosphatemia: A possible association? 2083 91

Autism is a neurodevelopmental disorder with symptoms arising that are apparent throughout the patient's lifespan. Autism Spectrum Disorders (ASD) are characterised by impaired social and communication interactions as well as restricted, repetitive interests and behaviour. Currently in Poland, about 50 000 people suffer from autism, of which 1/5 are children. Epidemiological studies show that the incidence of autism is increasing, which may be due to the diagnostic category of ASD having been developed. Of vital importance in the treatment of autism, is early diagnosis which is conducive to more rapidly improving the quality of patients' health. It is believed that both genetic and environmental factors may affect the development of the disease. Moreover, expert opinion emphasises the importance of making an adequate diagnosis when the first symptoms of autism start appearing which can be both psychological, gastro-intestinal and metabolic ones. Conventional treatment is based on the combination of behavioural and dietary therapy together with pharmacotherapy. For example, adapting an appropriate diet could help alleviate the disease severity, as well as the psychological and gastrointestinal symptoms. Much scientific research has indicated that pathogenesis of autism may have a beginning already in foetal life. During pregnancy, specialists should take special heed of metabolic disorders, which can increase the risk ofASD in children. One of the dietician's tasks are to properly assess the nutritional status of mothers before and during pregnancy, thereby allowing changes in nutrition to be made wherever necessary in order that metabolic indicators be improved. Thus an important part of autism therapy is the improving patient's nutritional status to prevent the onset of gastrointestinal symptoms. Adopting diets and tailored to individual disease symptoms, is linked to the nutritional requirements and food preferences of the patient. Specialists also emphasise that continual monitoring of the diet and nutritional status of children with ASD is required. It is also essential to start adequate dietary management in autistic patients with overweight, obesity or wasting, caused by improper nutrition. Frequently only a dietary therapy is insufficient to effectively treat autism. Many studies demonstrate the need to supplement the nutritional deficiencies of autistic patients with fatty acids omega-3, probiotics, vitamins and minerals in combination with medical and psychological interventions. A properly designed elimination diet adapted to the patient's individual may also lead to relief of the autism symptoms and the occurrence of gastrointestinal disorders. Parents and caregivers should therefore be aware of the benefits of nutritional therapy and need for proper monitoring the treatment of patients with ASD. A review of nutritional factors, dietary treatments and diet supplementation in patients with ASD is presented.
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PMID:How nutritional status, diet and dietary supplements can affect autism. A review. 2378 6

Rett syndrome (RTT) is an autism spectrum disorder caused by loss-of-function mutations in the gene encoding MeCP2, an epigenetic modulator that binds the methyl CpG dinucleotide in target genes to regulate transcription. Previously, we and others reported a role of microglia in the pathophysiology of RTT. To understand the mechanism of microglia dysfunction in RTT, we identified a MeCP2 target gene, SLC38A1, which encodes a major glutamine transporter (SNAT1), and characterized its role in microglia. We found that MeCP2 acts as a microglia-specific transcriptional repressor of SNAT1. Because glutamine is mainly metabolized in the mitochondria, where it is used as an energy substrate and a precursor for glutamate production, we hypothesize that SNAT1 overexpression in MeCP2-deficient microglia would impair the glutamine homeostasis, resulting in mitochondrial dysfunction as well as microglial neurotoxicity because of glutamate overproduction. Supporting this hypothesis, we found that MeCP2 downregulation or SNAT1 overexpression in microglia resulted in (1) glutamine-dependent decrease in microglial viability, which was corroborated by reduced microglia counts in the brains of MECP2 knock-out mice; (2) proliferation of mitochondria and enhanced mitochondrial production of reactive oxygen species; (3) increased oxygen consumption but decreased ATP production (an energy-wasting state); and (4) overproduction of glutamate that caused NMDA receptor-dependent neurotoxicity. The abnormalities could be rectified by mitochondria-targeted expression of catalase and a mitochondria-targeted peptide antioxidant, Szeto-Schiller 31. Our results reveal a novel mechanism via which MeCP2 regulates bioenergetic pathways in microglia and suggest a therapeutic potential of mitochondria-targeted antioxidants for RTT.
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PMID:Dysregulation of glutamine transporter SNAT1 in Rett syndrome microglia: a mechanism for mitochondrial dysfunction and neurotoxicity. 2567 46

Kir4.1 is an inwardly rectifying K(+) channel expressed exclusively in glial cells in the central nervous system. In glia, Kir4.1 is implicated in several functions including extracellular K(+) homeostasis, maintenance of astrocyte resting membrane potential, cell volume regulation, and facilitation of glutamate uptake. Knockout of Kir4.1 in rodent models leads to severe neurological deficits, including ataxia, seizures, sensorineural deafness, and early postnatal death. Accumulating evidence indicates that Kir4.1 plays an integral role in the central nervous system, prompting many laboratories to study the potential role that Kir4.1 plays in human disease. In this article, we review the growing evidence implicating Kir4.1 in a wide array of neurological disease. Recent literature suggests Kir4.1 dysfunction facilitates neuronal hyperexcitability and may contribute to epilepsy. Genetic screens demonstrate that mutations of KCNJ10, the gene encoding Kir4.1, causes SeSAME/EAST syndrome, which is characterized by early onset seizures, compromised verbal and motor skills, profound cognitive deficits, and salt-wasting. KCNJ10 has also been linked to developmental disorders including autism. Cerebral trauma, ischemia, and inflammation are all associated with decreased astrocytic Kir4.1 current amplitude and astrocytic dysfunction. Additionally, neurodegenerative diseases such as Alzheimer disease and amyotrophic lateral sclerosis demonstrate loss of Kir4.1. This is particularly exciting in the context of Huntington disease, another neurodegenerative disorder in which restoration of Kir4.1 ameliorated motor deficits, decreased medium spiny neuron hyperexcitability, and extended survival in mouse models. Understanding the expression and regulation of Kir4.1 will be critical in determining if this channel can be exploited for therapeutic benefit.
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PMID:The role of glial-specific Kir4.1 in normal and pathological states of the CNS. 2696 Dec 51

Hippocrates stated in 460-C.370 BC that, "All diseases begin in the Gut." This statement may be beginning to have meanings in the advent of new diseases such as Nodding Syndrome (NS) and Autism Spectrum Disorder (ASD). Interestingly, a recent publication from China in the journal of microbiology in 2017 suggests that high grain diet had dynamically shifted the composition of mucosa-associated microbiota and induced mucosal Injuries in the colon of Sheep. NS is a devastating childhood neurological disorder characterized by atonic seizure, cognitive impairment, head nodding, wasting and stunted growth. In addition, NS in Northern Uganda is clustered in time (those who were in IDPs), in space (discretely observed on either sides of the two rivers of Aswa and Pager) and in person (onset mainly between the ages of 5-15 years) and therefore exhibits spatial temporality. The first case of NS was noticed in Kitgum district in 1997, one year after the reported displacement of that community into IDP. Prior to that internal displacement, there were no reported cases of NS. The same scenario occurred in the IDPs of Odek, Gulu district where the population was displaced into IDPs in 2001 and approximately a year later in 2002, cases of NS began to appear. In the IDPs, children that eventually developed NS fed nearly exclusively on food ration provided by relief agencies and roughly a year later, cases of NS began to appear. In the other East African countries, there were no reported cases of NS prior to internal displacement and dependence on food ration. The observed common factors in the three East African regions where NS occurs at endemic proportion are perhaps: Internal displacement and feeding on relief food. These researchers suggest that NS may have perhaps resulted from dietary and environmental factors during IDPs which may have been foreign to their GIT and links this observation to the concept of microbiota-gut-brain axis.
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PMID:Could Nodding Syndrome (NS) in Northern Uganda be an environmentally induced alteration of ancestral microbiota? 3108 13