Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Similar movement disorders developed in two 8-year-old retarded children while they were receiving phenytoin. Seizures subsequent to a diphtheria-pertussis-tetanus immunization had developed in each child at 1 to 2 months of age. A static encephalopathy ensued, characterized by mental retardation, ataxia, spasticity, and a mixed seizure disorder. Intermittent dystonia and choreoathetosis developed insidiously while serum phenytoin concentrations were in the therapeutic range. Sustained dystonia and choreoatheosis developed 2 hours after an oral provocation with phenytoin. The baseline abnormalities on the electroencephalogram remained unchanged during the choreoathetosis. Recognizable metabolic abnormalities known to be associated with similar movement disorders were excluded. It was concluded from these studies that the movement disorder is secondary to phenytoin and can occur at therapeutic serum concentrations. Phenytoin is a central anticholinergic agent and a central stimulant of serotonin, and may induce movement disorders as a result of altering these neurotransmitters in the brain. The variable expression of these movement disorders may relate to the nature of the preexisting striatal insult.
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PMID:Phenytoin-induced dystonia and choreoathetosis in two retarded epileptic children. 94 1

Twenty-four Turkish children who had had neonatal tetanus were evaluated by means of physical and neurological examinations and psychometric tests at four to 15 years of age. Enuresis, mental retardation and growth retardation were frequent findings. The prevention of neonatal tetanus is important not only because of the high mortality rate but also because of its sequelae.
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PMID:Long-term prognosis after neonatal tetanus. 292 Aug 74

The amino acid proline has long been suspected to serve as a modulator of synaptic transmission in the mammalian brain, but no such function has been identified. The selective expression of high affinity proline transport by a subset of glutamate pathways suggested that proline might play a role in synaptic transmission at these sites. This idea was tested with use of one such pathway, the Schaffer collateral-commissural projection to CA1 pyramidal cells of the rat hippocampus. Proline enhanced the initial slope of the field EPSP without affecting axonal excitability or the magnitude of paired-pulse facilitation. Proline-induced potentiation far outlasted the period of proline application and required the activation of NMDA receptors. Proline enhanced Schaffer collateral-commissural synaptic transmission even when the connections between areas CA1 and CA3 had been interrupted. Potentiation was observed with a proline concentration normally present in human CSF (3 microM). A concentration typical of CSF in persons with the genetic disorder hyperprolinemia type II (30 microM) produced a somewhat greater effect. Occlusion experiments suggested that proline-induced potentiation and tetanus-induced long-term potentiation utilize largely distinct transduction mechanisms. Proline-induced potentiation could be blocked by a prior high frequency stimulus, whether or not the stimulus evoked long-term potentiation. These results suggest that endogenous extracellular proline regulates the basal function of some glutamate synapses by maintaining them in a partially potentiated state. They may also facilitate understanding of the seizures and/or mental retardation associated with genetic disorders of proline metabolism.
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PMID:Proline-induced potentiation of glutamate transmission. 925 26

We were initially highly skeptical that differences in the concentrations of thimerosal in vaccines would have any effect on the incidence rate of neurodevelopmental disorders after childhood immunization. This study presents the first epidemiologic evidence, based upon tens of millions of doses of vaccine administered in the United States, that associates increasing thimerosal from vaccines with neurodevelopmental disorders. Specifically, an analysis of the Vaccine Adverse Events Reporting System (VAERS) database showed statistical increases in the incidence rate of autism (relative risk [RR] = 6.0), mental retardation (RR = 6.1), and speech disorders (RR = 2.2) after thimerosal-containing diphtheria, tetanus, and acellular pertussis (DTaP) vaccines in comparison with thimerosal-free DTaP vaccines. The male/female ratio indicated that autism (17) and speech disorders (2.3) were reported more in males than females after thimerosal-containing DTaP vaccines, whereas mental retardation (1.2) was more evenly reported among male and female vaccine recipients. Controls were employed to determine if biases were present in the data, but none were found. It was determined that overall adverse reactions were reported in similar-aged populations after thimerosal-containing DTaP (2.4 +/- 3.2 years old) and thimerosal-free DTaP (2.1 +/- 2.8 years old) vaccinations. Acute control adverse reactions such as deaths (RR = 1.0), vasculitis (RR = 1.2), seizures (RR = 1.6), ED visits (RR = 1.4), total adverse reactions (RR = 1.4), and gastroenteritis (RR = 1.1) were reported similarly after thimerosal-containing and thimerosal-free DTaP vaccines. An association between neurodevelopmental disorders and thimerosal-containing DTaP vaccines was found, but additional studies should be conducted to confirm and extend this study.
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PMID:Neurodevelopmental disorders after thimerosal-containing vaccines: a brief communication. 1453 May 5

The authors previously published the first epidemiological study from the United States associating thimerosal from childhood vaccines with neurodevelopmental disorders (NDs) based upon assessment of the Vaccine Adverse Event Reporting System (VAERS). A number of years have gone by since their previous analysis of the VAERS. The present study was undertaken to determine whether the previously observed effect between thimerosal-containing childhood vaccines and NDs are still apparent in the VAERS as children have had a chance to further mature and potentially be diagnosed with additional NDs. In the present study, a cohort of children receiving thimerosal-containing diphtheria-tetanus-acellular pertussis (DTaP) vaccines in comparison to a cohort of children receiving thimerosal-free DTaP vaccines administered from 1997 through 2000 based upon an assessment of adverse events reported to the VAERS were evaluated. It was determined that there were significantly increased odds ratios (ORs) for autism (OR = 1.8, p < .05), mental retardation (OR = 2.6, p < .002), speech disorder (OR = 2.1, p < .02), personality disorders (OR = 2.6, p < .01), and thinking abnormality (OR = 8.2, p < .01) adverse events reported to the VAERS following thimerosal-containing DTaP vaccines in comparison to thimerosal-free DTaP vaccines. Potential confounders and reporting biases were found to be minimal in this assessment of the VAERS. It was observed, even though the media has reported a potential association between autism and thimerosal exposure, that the other NDs analyzed in this assessment of the VAERS had significantly higher ORs than autism following thimerosal-containing DTaP vaccines in comparison to thimerosal-free DTaP vaccines. The present study provides additional epidemiological evidence supporting previous epidemiological, clinical and experimental evidence that administration of thimerosal-containing vaccines in the United States resulted in a significant number of children developing NDs.
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PMID:Neurodevelopmental disorders following thimerosal-containing childhood immunizations: a follow-up analysis. 1576 92

Kabuki syndrome (KS) is associated with multiple organ system involvement. Characteristic features include long palpebral fissures with everted lower lids, prominent ears, skeletal abnormalities, mental retardation, and short stature. An increased incidence of infection has been reported in KS, and a few patients have been noted to have immune defects. However, the frequency and severity of the immune deficiency has not been clearly defined. Immunologic evaluation of 19 consecutive individuals with KS was performed at The Children's Hospital of Philadelphia. Decreased IgA levels were noted in 15/19 individuals (79%), 2 of whom had undetectable levels. Eight patients (42%) also had low total IgG levels. Specific IgG subclass abnormalities were found in 6 of 13 patients evaluated. IgM levels were less frequently decreased. One patient failed to generate anti-tetanus antibodies despite immunization. This study suggests that hypogammaglobulinemia is a frequent finding in children with KS. The pattern of antibody abnormalities seen in children with KS resembles common variable immune deficiency (CVID). Due to this increased susceptibility to infection, children with KS should have immunologic evaluations at the time of diagnosis in order to reduce preventable morbidity and mortality.
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PMID:Immune abnormalities are a frequent manifestation of Kabuki syndrome. 1588 82

Thimerosal is an ethylmercury (49.55% mercury by weight) preservative historically added to some vaccines. Toxicokinetic studies showed children in the United States received doses of mercury from Thimerosal-containing vaccines (TCVs) in excess of safety guidelines. In the United States during the 1990s, diphtheria-tetanus-pertussis (DTP) and Haemophilus influenzae type b (Hib) vaccines (maximally, 50 mug mercury per joint administration) and diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTPH) vaccines (25 mug mercury per administration) were given to children in the same childhood vaccination schedule at 2, 4, 6, and 15-18 mo, so that children receiving DTP and Hib vaccines may have maximally received an additional 100 mug more mercury exposure from TCVs than children administered DTPH vaccines. A case-control epidemiological study of neurodevelopmental disorders (NDs) reported to the Vaccine Adverse Event Reporting System (VAERS) (online public access version; updated 31 August 2004) following administration of DTP vaccines in comparison DTPH vaccines manufactured by Lederle Laboratories (Pearl River, NY) from 1994 through 1998 was undertaken. Significantly increased odds ratios for autism, speech disorders, mental retardation, infantile spasms, and thinking abnormalities reported to VAERS were found following DTP vaccines in comparison to DTPH vaccines with minimal bias or systematic error. Additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially since in 2005 the Institute of Medicine issued a report calling into question handling of vaccine safety data by the National Immunization Program of the Centers for Disease Control and Prevention.
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PMID:An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States. 1676 80

Activity-dependent synaptic remodeling occurs during early-use critical periods, when naive juveniles experience sensory input. Fragile X mental retardation protein (FMRP) sculpts synaptic refinement in an activity sensor mechanism based on sensory cues, with FMRP loss causing the most common heritable autism spectrum disorder (ASD), fragile X syndrome (FXS). In the well-mapped Drosophila olfactory circuitry, projection neurons (PNs) relay peripheral sensory information to the central brain mushroom body (MB) learning/memory center. FMRP-null PNs reduce synaptic branching and enlarge boutons, with ultrastructural and synaptic reconstitution MB connectivity defects. Critical period activity modulation via odorant stimuli, optogenetics, and transgenic tetanus toxin neurotransmission block show that elevated PN activity phenocopies FMRP-null defects, whereas PN silencing causes opposing changes. FMRP-null PNs lose activity-dependent synaptic modulation, with impairments restricted to the critical period. We conclude that FMRP is absolutely required for experience-dependent changes in synaptic connectivity during the developmental critical period of neural circuit optimization for sensory input.
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PMID:Fragile X Mental Retardation Protein Requirements in Activity-Dependent Critical Period Neural Circuit Refinement. 2875 46