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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reelin is a large extracellular glycoprotein that is defective in reeler mutant mice and plays a well-established role during brain development in human as well as rodents. In the adult brain, Reelin is expressed in a subset of GABAergic interneurons. Its role in disease states is not clearly defined, although it is implicated in autism and psychoses such as schizophrenia. In this report, we show that Reelin immunoreactive proteins can be detected in the human cerebrospinal fluid (CSF) with monoclonal antibodies directed against the N- and C-terminal regions of the protein. In CSF, Reelin is present as different products due to processing at two main sites; preservation at -20 degrees C increases processing further. CSF Reelin originates from the brain tissue and not from plasma. The protein was detected in comparable concentrations in children and adults, and the signal varied largely from subject to subject with no obvious correlation with age or neurological disease state.
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PMID:Characterization of the various forms of the Reelin protein in the cerebrospinal fluid of normal subjects and in neurological diseases. 1500 2

Mortality risk assessment of juvenile life insurance applicants with impairments can be challenging. Advances in neonatal care means more premature infants will survive into childhood and adulthood with attendant respiratory and neurologic disorders. The degree of neonatal lung disease and length of ventilator support are factors that help to separate out more favorable risks. Autism and other developmental disorders have diverse presentations, but in the absence of other neurologic conditions risks are generally limited to accidents. Children with attention deficit hyperactivity disorder without accompanying conduct disorder are less likely to have problems with drug abuse. Impaired pediatric lives mortality patterns depend on whether accidental death predominates.
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PMID:Pediatric issues in underwriting. 1606 May 43

Systemic immune abnormalities have no known relevance to brain dysfunction in autism. In order to find evidence for neuroinflammation, we compared levels of sensitive indicators of immune activation: quinolinic acid, neopterin, and biopterin, as well as multiple cytokines and cytokine receptors, in cerebrospinal fluid and serum from children with autism, to control subjects with other neurologic disorders. In cerebrospinal fluid from 12 children with autism, quinolinic acid (P = 0.037) and neopterin (P = 0.003) were decreased, and biopterin (P = 0.040) was elevated, compared with control subjects. In sera from 35 persons with autism, among cytokines, only tumor necrosis factor receptor II was elevated compared with controls (P < 0.02). Decreased quinolinic acid and neopterin in cerebrospinal fluid are paradoxical and suggest dysmaturation of metabolic pathways and absence of concurrent infection, respectively, in autism. Alternatively, they may be produced by microglia but remain localized and not expressed in cerebrospinal fluid.
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PMID:Cerebrospinal fluid and serum markers of inflammation in autism. 1663 16

Autistic spectrum disorders can be associated with mitochondrial dysfunction. We present a singleton case of developmental regression and oxidative phosphorylation disorder in a 19-month-old girl. Subtle abnormalities in the serum creatine kinase level, aspartate aminotransferase, and serum bicarbonate led us to perform a muscle biopsy, which showed type I myofiber atrophy, increased lipid content, and reduced cytochrome c oxidase activity. There were marked reductions in enzymatic activities for complex I and III. Complex IV (cytochrome c oxidase) activity was near the 5% confidence level. To determine the frequency of routine laboratory abnormalities in similar patients, we performed a retrospective study including 159 patients with autism (Diagnostic and Statistical Manual of Mental Disorders-IV and Childhood Autism Rating Scale) not previously diagnosed with metabolic disorders and 94 age-matched controls with other neurologic disorders. Aspartate aminotransferase was elevated in 38% of patients with autism compared with 15% of controls (P <.0001). The serum creatine kinase level also was abnormally elevated in 22 (47%) of 47 patients with autism. These data suggest that further metabolic evaluation is indicated in autistic patients and that defects of oxidative phosphorylation might be prevalent.
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PMID:Developmental regression and mitochondrial dysfunction in a child with autism. 1882 80

Autism is a behaviorally defined neurodevelopmental disorder usually diagnosed in early childhood that is characterized by impairment in reciprocal communication and speech, repetitive behaviors, and social withdrawal. Although both genetic and environmental factors are thought to be involved, none have been reproducibly identified. The metabolic phenotype of an individual reflects the influence of endogenous and exogenous factors on genotype. As such, it provides a window through which the interactive impact of genes and environment may be viewed and relevant susceptibility factors identified. Although abnormal methionine metabolism has been associated with other neurologic disorders, these pathways and related polymorphisms have not been evaluated in autistic children. Plasma levels of metabolites in methionine transmethylation and transsulfuration pathways were measured in 80 autistic and 73 control children. In addition, common polymorphic variants known to modulate these metabolic pathways were evaluated in 360 autistic children and 205 controls. The metabolic results indicated that plasma methionine and the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), an indicator of methylation capacity, were significantly decreased in the autistic children relative to age-matched controls. In addition, plasma levels of cysteine, glutathione, and the ratio of reduced to oxidized glutathione, an indication of antioxidant capacity and redox homeostasis, were significantly decreased. Differences in allele frequency and/or significant gene-gene interactions were found for relevant genes encoding the reduced folate carrier (RFC 80G > A), transcobalamin II (TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A), methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A > C), and glutathione-S-transferase (GST M1). We propose that an increased vulnerability to oxidative stress (endogenous or environmental) may contribute to the development and clinical manifestations of autism.
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PMID:Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. 1691 39

In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All participants were screened through the nationwide Danish National Hospital Register (DNHR). We inquired about epilepsy and other neurological diseases during an observation period of 27 years. A similar proportion of case- and control mothers had a diagnosis of any neurological disease, 9.9% vs 10.6%. For case fathers the proportion was 5.7% vs 9.7%. No single neurological disease was significantly more frequent among parents of persons with IA. Our study lent support to the notion that epilepsy and other neurological diseases are not part of the broader IA phenotype.
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PMID:Epilepsy and other neurological diseases in the parents of children with infantile autism. A case control study. 1756 32

Rett and Angelman syndromes comprise part of the spectrum of neurologic disorders associated with autism. Their clinical presentations overlap, with both presenting in later infancy with global developmental delays, severe speech and communication impairments, progressive microcephaly, seizures, autistic behaviors, and characteristic albeit different movement disorders and stereotypic hand movements. Although other features can help differentiate these disorders, significant phenotypic overlap and variation in severity sometimes cloud the underlying diagnosis. Rett syndrome is caused by a mutation in the MECP2 gene located on Xq28, whereas Angelman syndrome results from the loss of UBE3A function on chromosomal region 15q11-q13 related to a variety of molecular genetic mechanisms. Recent advances have uncovered interactions between these and other genes that affect the function and structure of neurons in the brain. The reversal of symptoms of Rett syndrome in a mature mouse model suggests the possibility for treatment of these and perhaps other autism-related disorders in the future.
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PMID:The overlapping spectrum of rett and angelman syndromes: a clinical review. 1798 Mar 7

Cortical interneuron dysfunction has been implicated in multiple human disorders including forms of epilepsy, mental retardation, and autism. Although significant advances have been made, understanding the biologic basis of these disorders will require a level of anatomic, molecular, and genetic detail of interneuron development that currently does not exist. To further delineate the pathways modulating interneuron development we performed fluorescent activated cell sorting (FACs) on genetically engineered mouse embryos that selectively express green fluorescent protein (GFP) in developing interneurons followed by whole genome microarray expression profiling on the isolated cells. Bioinformatics analysis revealed expression of both predicted and unexpected genes in developing cortical interneurons. Two unanticipated pathways discovered to be up regulated prior to interneurons differentiating in the cortex were ion channels/neurotransmitters and synaptic/vesicular related genes. A significant association of neurological disease related genes to the population of developing interneurons was found. These results have defined new and potentially important data on gene expression changes during the development of cortical interneurons. In addition, these data can be mined to uncover numerous novel genes involved in the generation of interneurons and may suggest genes/pathways potentially involved in a number of human neurological disorders.
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PMID:FACS-array gene expression analysis during early development of mouse telencephalic interneurons. 1817 91

Autism spectrum disorder is a complex developmental disorder that dramatically affects the lives of patients and their families and the broader community. The causes of autism are unknown; however, evidence increasingly suggests that a complex interplay among environmental stressors, genetic mutations, and other biological factors likely plays a significant role in the development and/or progression of autism spectrum disorder. On April 18 and 19, 2007, the Institute of Medicine's Forum on Neuroscience and Nervous System Disorders hosted a workshop to provide a venue to bring together scientists; major sponsors of autism-related research; and members of the autism patient, family, and advocacy community to discuss the most promising and urgent scientific questions and opportunities. Broad participation by the autism community enriched the meeting significantly by contributing a valuable and personal perspective that is often missing from scientific meetings. It also began a much improved public-private partnership in which all stakeholders are represented. On the basis of the presentations and the discussions that followed, an array of important scientific opportunities were identified in 5 general categories: (1) opportunities to advance clinical research; (2) opportunities to enhance epidemiologic studies; (3) opportunities to improve the understanding of autism's pathology and etiology; (4) tools and infrastructure needs; and (5) opportunities for public-private partnerships. This workshop demonstrated that full public engagement can greatly enhance activities such as this workshop and its outcomes. Furthermore, we expect that this listing of scientific challenges, needs, and opportunities will help to frame a more comprehensive research agenda.
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PMID:Autism and the environment: challenges and opportunities for research. 1851 93

The methyl-CpG-binding protein MeCP2 was discovered over 15 years ago as part of a search for proteins that selectively bind methylated DNA. It is a nuclear protein that is largely chromatin-bound and has a strong preference for binding to methylated DNA sequences in vivo. Evidence from model systems shows that MeCP2 can recruit the Sin3a co-repressor complex to promoters leading to transcriptional repression, therefore suggesting that MeCP2 can interpret the DNA methylation signal to bring about gene silencing. Mutations in the human MECP2 gene cause the autism spectrum disorder Rett Syndrome. MeCP2 is most highly expressed in neurons, and mice lacking this protein show symptoms that strikingly parallel those of Rett patients. Surprisingly, these symptoms are efficiently reversed by delayed activation of a 'stopped' Mecp2 gene, raising hopes that human Rett syndrome may also be reversible. Future studies of MeCP2 promise to shed light upon brain function, neurological disease and the biology of DNA methylation.
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PMID:The methyl-CpG-binding protein MeCP2 and neurological disease. 1863 Nov 20


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