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

The platelet levels of serotonin and the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were measured in 18 drug-free autistic (DSM-III criteria) and 14 age-matched healthy children. Serotonin was significantly increased while the amino acids aspartic acid, glutamine, glutamic acid and gamma-aminobutyric acid were significantly decreased in comparison with the controls. It is suggested that the decline of the amino acids in platelets from autistic children represents a biochemical marker related to infantile autism.
 ...
PMID:Serotonin and amino acid content in platelets of autistic children. 851 70

Twelve diseases, most with neuropsychiatric features, arise from trinucleotide repeat expansion mutations. Expansion mutations may also cause a number of other disorders, including several additional forms of spinocerebellar ataxia, bipolar affective disorder, schizophrenia, and autism. To obtain candiate genes for these disorders, cDNA libraries from adult and fetal human brain were screened at high stringency for clones containing CAG repeats. Nineteen cDNAs were isolated and mapped to chromosomes 1, 2, 4, 6, 7, 8, 9, 12, 16, 19, 20, and X. The clones contain between 4 and 17 consecutive CAG, CTG, TCG, or GCA triplets. Clone H44 encodes 40 consecutive glutamines, more than any other entry in the nonredundant GenBank protein database and well within the range that causes neuronal degeneration in several of the glutamine expansion diseases. Eight cDNAs encode 15 or more consecutive glutamine residues, suggesting that the gene products may function as transcription factors, with a potential role in the regulation of neurodevelopment or neuroplasticity. In particular, the conceptual translation of clone CTG3a contains 18 consecutive glutamines and is 45% identical to the C-terminal 306 residues of the mouse numb gene product. These genes are therefore candidates for diseases featuring anticipation, neurodegeneration, or abnormalities of neurodevelopment.
 ...
PMID:cDNAs with long CAG trinucleotide repeats from human brain. 922 80

A mutation in the gene FOXP2 was recently identified as being responsible for a complicated speech and language phenotype in a single large extended pedigree. This gene is of interest to autism because it lies in one of the most consistently linked autism chromosomal regions of interest. We therefore tested this gene for its involvement in autism in a large sample of autism families. We completely sequenced the exon containing the mutation, screened the remaining coding sequence using SSCP technology, and identified and genotyped two novel intronic tetranucleotide repeat polymorphisms that were then analyzed for evidence of linkage and linkage disequilibrium (LD). We identified two families in which heterozygous deletions of a small number of glutamines in a long poly-glutamine stretch were found in one parent and the autistic probands; no other non-conservative coding sequence changes were identified. Linkage and LD analyses were performed in 75 affected sibling pair families and in two subgroups of this sample defined by the presence/absence of severe language impairment. One allele appeared to have an opposite pattern of transmission in the language based subgroups, but otherwise the linkage and LD analyses were negative. We conclude that FOXP2 is unlikely to contribute significantly to autism susceptibility.
 ...
PMID:Evaluation of FOXP2 as an autism susceptibility gene. 1211 95

Plasma amino acid levels were measured in autistic and Asperger syndrome patients, their siblings, and parents. The results were compared with values from age-matched controls. Patients with autism or Asperger syndrome and their siblings and parents all had raised glutamic acid, phenylalanine, asparagine, tyrosine, alanine, and lysine (p < .05) than controls, with reduced plasma glutamine. Other amino acids were at normal levels. These results show that children with autistic spectrum disorders come from a family background of dysregulated amino acid metabolism and provide further evidence for an underlying biochemical basis for the condition.
J Autism Dev Disord 2003 Feb
PMID:Plasma amino acid levels in children with autism and their families. 1270 84

The substrate-binding sites in membrane transporters are alternately accessible from either side of the membrane, but the molecular basis of how this alternate opening of internal and external gates is achieved is largely unknown. Here we present data indicating that, in the neuronal electrogenic sodium- and potassium-coupled glutamate transporter EAAC-1, the substrate-binding site and one of the gates, or a residue controlling the gating process, are in close physical proximity. Arginine 445, located only two residues away from a residue implicated in glutamate binding (Bendahan, A., Armon, A., Madani, N., Kavanaugh, M. P., and Kanner, B. I. (2000) J. Biol. Chem. 275, 37436-37442), has been mutated to serine (R445S). Upon expression in oocytes, measurements of l-[(3)H]-glutamate transport under voltage clamp reveal that the charge/flux ratio for l-glutamate at -60 mV is approximately 30-fold higher than that of the wild type. Also, with d-aspartate, R445S exhibits an approximately 15-fold increase in this ratio. In contrast to the wild type, the reversal potential of the substrate-dependent currents in R445S shifts to more negative potentials when either the external sodium or potassium concentration is decreased. These findings indicate that these two cations are the main current carriers in the R445S mutant. Introduction of a methionine or a glutamine, but not a lysine, at position 445 gives rise to a phenotype similar to R445S. Therefore, it seems that the elimination of a positive charge in the vicinity of the substrate-binding site converts the transporter into a glutamate-gated cation-conducting pathway.
 ...
PMID:Arginine 445 controls the coupling between glutamate and cations in the neuronal transporter EAAC-1. 1459 97

We analyzed the FOXP2 gene, which encodes a putative transcription factor containing a polyglutamine tract and a forkhead DNA-binding domain, for a possible causative mutation in autism. FOXP2 was reported to be mutated in patients with a severe speech and language disorder. FOXP2 was located on chromosome 7q31, which is one of the loci involved in autism. Autism and specific language impairment share some of their clinical phenotypes. In addition, FOXP2 was expressed abundantly in the brain. We screened all of the exons of FOXP2 for causative mutations in 53 Japanese autistic patients using denaturing high-performance liquid chromatography and direct sequencing. A delCAA in exon 5 causing one glutamine deletion in the first polyglutamine tract was detected in four patients and in 2 of 50 control individuals. The frequency of the TT allele with the G to T base change in intron 15 was significantly high in the autistic population. The other base changes included one silent base change (A569G) in exon 5 and three in introns. Our results may suggest a relationship between autism and the FOXP2 gene or a gene located nearby.
 ...
PMID:Absence of causative mutations and presence of autism-related allele in FOXP2 in Japanese autistic patients. 1573 2

Because boys are four times more likely than girls to develop autism, the role of male hormones (androgens) has received considerable scrutiny. Some researchers implicate arginine vasopressin, an androgen-dependent hormone from the pituitary gland that elicits male behavior. Elevated vasopressin is also the most common cause of low blood sodium (hyponatremia)--most serious in the brains of children. Hyponatremia causes astrocytes to swell, then release the amino acids taurine and glutamine and their water to compensate. Taurin--the brain osmolyte/inhibitory neurotransmitter that suppresses vasopressin--was the amino acid most wasted or depleted in urine of autistic children. Glutamine is a critical metabolic fuel in brain neurons, astrocytes, endothelial cells, and the intestines, especially during hypoglycemia. Because glutamine is not thought to cross the blood-brain barrier significantly, the implications of low blood glutamine in these children are not recognized. Yet children with high brain glutamine from urea cycle disorders are rarely diagnosed with autistic disorders. Other common events in autistic children that release vasopressin are gastrointestinal inflammation, hypoglycemia, and stress. Signs of hyponatremia in these children are salt cravings reported online and anecdotally, deep yellow urine revealing concentration, and relief of autistic behavior by fluid/salt diets. Several interventions offer promise: (a) taurine to suppress vasopressin and replenish astrocytes; (b) glutamine as fuel for intestines and brain; (c) arginine to spare glutamine, detoxify ammonia, and increase brain blood flow; and (d) oral rehydration salts to compensate dilutional hyponatremia. This hypothesis appears eminently testable: Does your child crave salt? Is his urine deep yellow?
 ...
PMID:Do salt cravings in children with autistic disorders reveal low blood sodium depleting brain taurine and glutamine? 2192 97

Recent research in autism spectrum disorder (ASD) has aroused interest in anterior cingulate cortex and in the neurometabolite glutamate. We report two studies of pregenual anterior cingulate cortex (pACC) in pediatric ASD. First, we acquired in vivo single-voxel proton magnetic resonance spectroscopy ((1)H MRS) in 8 children with ASD and 10 typically developing controls who were well matched for age, but with fewer males and higher IQ. In the ASD group in midline pACC, we found mean 17.7% elevation of glutamate + glutamine (Glx) (p<0.05) and 21.2% (p<0.001) decrement in creatine + phosphocreatine (Cr). We then performed a larger (26 subjects with ASD, 16 controls) follow-up study in samples now matched for age, gender, and IQ using proton magnetic resonance spectroscopic imaging ((1)H MRSI). Higher spatial resolution enabled bilateral pACC acquisition. Significant effects were restricted to right pACC where Glx (9.5%, p<0.05), Cr (6.7%, p<0.05), and N-acetyl-aspartate + N-acetyl-aspartyl-glutamate (10.2%, p<0.01) in the ASD sample were elevated above control. These two independent studies suggest hyperglutamatergia and other neurometabolic abnormalities in pACC in ASD, with possible right-lateralization. The hyperglutamatergic state may reflect an imbalance of excitation over inhibition in the brain as proposed in recent neurodevelopmental models of ASD.
 ...
PMID:Elevated glutamatergic compounds in pregenual anterior cingulate in pediatric autism spectrum disorder demonstrated by 1H MRS and 1H MRSI. 2284 44

First reported formally in 1980, the frequent ability of infectious fever to relieve autistic behavior, often dramatically (and rarely aggravate), has long tantalized parents, practitioners, and researchers - yet its physiology and biochemistry have never been investigated, to judge from the literature. Fever is a complex interplay of immune, metabolic, and stress responses, yet its benefit in autistic disorders (ASD) may derive largely from a single response - release of the amino acid glutamine from skeletal muscles as provisional fuel. This proposal is based on evidence of low blood and brain glutamine in ASD children and adults, notable lack of autistic behavior in children with high brain glutamine from urea cycle disorders, and other events that elicit dramatic improvements - fasting, panic, pain, and the corticosteroid prednisone - that release or synthesize glutamine. Glutamine released from muscles is metabolized by the intestines like ingested glutamine. If glutamine released by fever rarely aggravates autistic behavior, why would supplemental glutamine?
 ...
PMID:Does infectious fever relieve autistic behavior by releasing glutamine from skeletal muscles as provisional fuel? 2309 76

Increased glutamate levels have been reported in the hippocampal and frontal regions of persons with autism using proton magnetic resonance spectroscopy ((1)H-MRS). Although autism spectrum disorders (ASDs) are highly heritable, MRS studies have not included relatives of persons with ASD. We therefore conducted a study to determine if glutamate levels are elevated in people with autism and parents of children with autism. Single-voxel, point-resolved spectroscopy data were acquired at 3T for left and right hemisphere auditory cortical voxels in 13 adults with autism, 15 parents of children with autism, and 15 adult control subjects. The primary measure was glutamate + glutamine (Glx). Additional measures included n-acetyl-aspartate (NAA), choline (Cho), myoinositol (mI), and creatine (Cr). The autism group had significantly higher Glx, NAA, and Cr concentrations than the control subjects. Parents did not differ from control subjects on any measures. No significant differences in Cho or mI levels were seen among groups. No reliable correlations between autism symptom measures, and MRS variables were seen after Bonferroni correction for multiple comparisons. The elevation in Glx in autism is consistent with prior MRS data in the hippocampus and frontal lobe and may suggest increased cortical excitability. Increased NAA and Cr may indicate brain metabolism disturbances in autism. In the current study, we found no reliable evidence of a familial effect for any spectroscopy measure. This may indicate that these metabolites have no heritable component in autism, the presence of a compensatory factor in parents, or sample-specific limitations such as the participation of singleton families.
Autism Res 2013 Feb
PMID:Increased glutamate concentration in the auditory cortex of persons with autism and first-degree relatives: a (1)H-MRS study. 2316 3


1 2 3 4 Next >>