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)

Glycosphingolipids from brain, liver, and spleen of a patient with mucopolysaccharidosis type III B were quantitatively analyzed. Neutral glycosphingolipids containing glucosylceramide, lactosylceramide, globotriaosylceramide, globotetraosylceramide, and gangliotriaosylceramide were increased in the brain, while the contents of galactosylceramide and galactosylceramide I3-sulfate were decreased. The total ganglioside levels were low in the grey matter (522 micrograms N-acetylneuraminic acid/g) and high in the white matter (342 micrograms N-acetylneuraminic acid/g), when compared with the normal values (744-918 micrograms/g in grey matter and 80-180 micrograms/g in white matter). The ganglioside compositions were characterized by a high proportion of II3-N-acetylneuraminosylgangliotriaosylceramide (GM2), II3-N-acetylneuraminosyllactosylceramide (GM3), and II3-(N-acetylneuraminosyl)2lactosylceramide (GD3). An unusual band of protein in place of an ordinary band of Wolfgram protein was detected as a major band by sodium dodecylsulfate-polyacrylamide gel electrophoresis. The low levels of 4-eicosasphingenine in the brain gangliosides indicated that the disturbance of the sphingolipid metabolism already began at age 3 at the latest and that the brain remained immature. These abnormal glycosphingolipids and protein as well as the accumulation of heparan sulfate explain in part the severe progressive mental retardation which is most characteristic of the mucopolysaccharidosis III B. Abnormalities of glycosphingolipids in the liver and spleen are also found.
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PMID:Abnormalities of glycosphingolipids in mucopolysaccharidosis type III B. 642 55

Sphingolipid activator protein-1 (SAP-1) is a glycoprotein found in human tissue extracts that stimulates the enzymatic hydrolysis of at least two glycosphingolipids, including GM1 ganglioside and sulfatide. The ability of purified SAP-1 to stimulate GM1 ganglioside hydrolysis by extracts of cultured fibroblasts from patients with beta-galactosidase deficiency was examined, and all patients had a pronounced deficiency (under 10% of control). Using monospecific antibodies against SAP-1, the concentration was determined in cultured fibroblasts by rocket immunoelectrophoresis. Extracts from 15 control cell lines were found to have 0.72 +/- 0.24 micrograms cross-reactive material/mg protein, while cell extracts from 8 patients with GM1 gangliosidosis involving mental retardation were found to have 1.08 +/- 0.17, which is significantly elevated. When the fibroblast extracts were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroblotting, multiple bands were observed. Controls were found to have two major bands with estimated molecular weights of 9000 and 9500, and a minor band at 7800. Extracts from patients with GM1 gangliosidosis were found to have multiple bands ranging upward to 13,000. Extracts from patients with the most severe clinical types of GM1 gangliosidosis had almost exclusively high-molecular-weight forms (molecular weights above 10,000). Treatment of SAP-1 from control liver with endoglycosidase D caused a decrease in the Mr 9500 band and increased in the Mr 7800 band. When SAP-1 from GM1 gangliosidosis liver was treated sequentially with neuraminidase, beta-galactosidase, and endoglycosidase D, almost all of it was converted to the forms found in control human liver.
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PMID:Biochemical, immunological, and structural studies on a sphingolipid activator protein (SAP-1). 643 28

Prenatal exposure to oral anticoagulants during pregnancy may result in defective fetal development or life-threatening hemorrhage. Fetal exposure during the first eight weeks of pregnancy may cause abnormal development of the facial structures, hypoplastic digits, strippled epiphyses, and mental retardation. Midtrimester exposure may result in optic atrophy, faulty brain growth, and developmental retardation. Third-trimester exposure may produce fetal anticoagulation, predisposing the infant to life-threatening hemorrhage in the perinatal period. Anticoagulation with heparin sodium does not provide a clearly safe alternative, since this therapy has been associated with excessive fetal loss.
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PMID:Hazards of oral anticoagulants during pregnancy. 735 39

An adolescent boy with essential hypernatremia, absent corpus callosum, mental retardation, hypodipsia, and partial diabetes insipidus with "inappropriate" ADH regulation and secretion was studied regarding factors controlling ADH and neurophysin release. Persistent hyperosmolality was noted while on 100 mEq sodium intake daily. Endogenous vasopressin activity was demonstrated after prolonged water deprivation. Hypertonic saline infusion produced increased volumes but dilute urine. Aqueous pitressin increased urinary osmolality, decreased serum osmolality, urine flow rate, and free water clearance. Stable water diuresis was induced by water loading and on normal saline infusion. Nicotine-stimulated neurophysin remained unexpectedly low and below the level of detectability when sampled during the physiologic studies, whereas oestrogen-stimulated neurophysin was elevated during oestrogen stimulation, water loading, and orthostasis procedures. Plasma vasopressin was suppressed with water loading but remained suppressed 90 min after tilt table testing. These data indicate impairment of the osmoreceptor mechanism: however, since the patient had a normal response of oestrogen-stimulated neurophysin, that part of the neurohypophysis appears intact. Chlorpropamide was effective in alleviating the hyperosmolar state acutely and maintained normal osmolar concentrations during two years of therapy.
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PMID:Essential hypernatraemia, antidiuretic hormone and neurophysin secretion: response to chlorpropamide. 746

A 32-year-old man with mental retardation and uncontrolled complex partial epilepsy receiving carbamazepine (CBZ) and divalproex sodium (VPA), developed frequent episodes of forced upward gaze after increase in the daily VPA dosage. CBZ dosage was decreased, with prompt resolution of symptoms. The upward gaze problem recurred several months later. CBZ dosage was decreased further with subsequent resolution of symptoms. Therefore, the oculogyric crisis (OGC) appeared to be induced by CBZ.
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PMID:Oculogyric crisis induced by carbamazepine. 758 63

A new autosomal recessively inherited disease of the central nervous system involving childhood epilepsy and mental deterioration is described. Twenty three patients (11 males and 12 females) belonging to 11 families from northern Finland have been identified. A common ancestor has been found for nine families. The mean age of onset of epilepsy was 6.7 years (range 5-10 years) and the epilepsy was characterised by generalised tonic-clonic seizures increasing in frequency up to puberty. One third of the patients also had complex partial seizures during childhood. During young adulthood the epileptic activity began to decrease, but complete remission did not occur. Electroencephalography showed progressive slowing of the background activity with relatively scanty epileptiform activity. Out of four ictal recordings the paroxysmal activity was initiated focally in two cases. Clonazepam and sodium valproate had some antiepileptic effect, clonazepam being the more beneficial of the two. Mental development, which was originally normal, began to deteriorate two to five years after the onset of epilepsy, and the deterioration continued during adulthood in spite of good epilepsy control, leading to mental retardation by middle age. The pathogenesis of the disorder, called the Northern epilepsy syndrome, is unknown. Linkage analysis using DNA markers linked to the EPM1 gene for progressive myoclonus epilepsy of Unverricht-Lundborg type showed that the Northern epilepsy syndrome is not allelic to EPM1.
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PMID:Northern epilepsy syndrome: an inherited childhood onset epilepsy with associated mental deterioration. 801 63

Different aspects of psychopathology and folate metabolism were studied in a group of 150 adults from hospitals and the community who had mental retardation and epilepsy and compared with an individually matched control group of 150 adults with mental retardation but no epilepsy. Only 4.45% of those receiving anticonvulsant medication had a serum folate level below the normal laboratory reference range. Anticonvulsants other than sodium valproate tended to lower serum folate level. Results showed an inverse relation between the serum anticonvulsant levels and serum folate level. When the serum folate level of the adults with epilepsy who had either severe behavior problems and/or psychiatric illness and/or personality disorder was compared with the adults with epilepsy who did not have these disorders, no major significant intergroup difference emerged in serum folate level.
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PMID:Effect of folate metabolism on the psychopathology of adults with mental retardation and epilepsy. 805

The adverse effects of the maternal consumption of alcohol on the fetus have been recognized for centuries. Fetal alcohol syndrome is characterized by pre- and postnatal growth retardation, mental retardation, behavioral deficits, and facial deformities. Despite numerous animal studies, the biochemical mechanism(s) by which alcohol produces teratogenic effects on the developing fetus are not well understood. Several studies have shown that administration of alcohol to adult rats produces a decrease in hepatic levels of glutathione (GSH). In utero administration of alcohol has also been shown to produce a decrease in GSH levels, as well as prenatal growth retardation and intrauterine death. In an effort to determine if GSH may have a vital role in protecting the fetus against the teratogenic effects of alcohol, buthionine (SR)-sulfoximine (BSO) was used to deplete GSH levels in the mother and fetus. Timed pregnant Sprague-Dawley rats were placed on a liquid BioServ diet containing either 0%, 11%, 23%, 29%, 31%, 33%, or 35% ethanol-derived calories, with or without BSO (888 mg/kg/24 hr), starting on day 1 of pregnancy. Another set of mothers were fed lab chow and water as a control group for the liquid diet. The mothers were maintained on the diet until gestation day 21 when they were anesthetized with sodium pentobarbital and the pups delivered by cesarean section. The offspring were counted, weighed, killed, and the brain and liver weighed. The effects of BSO on the alcohol dose-response curves (body weights, brain weights, and litter number) were then determined to ascertain if a depletion in GSH potentiated the effects of alcohol. In utero administration of BSO, aside from the depletion of GSH in the liver and brain in the developing fetus, produced a shift to the left in the alcohol dose-response curve.
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PMID:Effects of buthionine sulfoximine on the outcome of the in utero administration of alcohol on fetal development. 890 78

The causes for mental retardation due to perinatal hypothyroidism are not fully understood. Here we show that the most potent component of thyroid hormone, 3,5,3'-triiodo-L-thyronine (T3), selectively increases the density of voltage-activated Na+ currents in hippocampal neurons from newborn rats. Thus, the well known effects of thyroid hormone on energy expenditure and Na+/K+ ATPase activity could to some extent result from the enhanced Na+ influx through voltage-activated Na+ channels. In addition, a down-regulation of the Na+ current density in neurons could contribute to some of the neurological symptoms accompanying hypothyroidism, including slowing of mentation, of neuronal conduction velocities, the alpha rhythm of the electroencephalogram, and increased latencies of evoked potentials and reflexes.
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PMID:Thyroid hormone regulates Na+ currents in cultured hippocampal neurons from postnatal rats. 910 52

Ornithine Transcarbamylase (OTC) is a key urea cycle enzyme. Congenital OTC deficiencies in humans result in hyperammonemia and a spectrum of neurological symptoms including hypotonia, seizures and mental retardation. Neuropathologic evaluation reveals cerebral atrophy, ventricular enlargement and Alzheimer type II astrocytosis. Using an animal model of congenital OTC deficiency, the sparse fur (spf) mouse, recent studies have revealed significant alterations of cholinergic, serotoninergic and glutamatergic neurotransmitter systems. Possible pathophysiologic mechanisms responsible for neuronal cell loss in OTC deficiency include a deficit in cerebral energy metabolism, and glutamate excitotoxicity. Therapy continues to rely on alternative substrate administration including sodium benzoate and sodium phenylacetate. Experimental evidence suggests that acetyl-L-carnitine and glutamate (NMDA) receptor antagonists could be potentially useful therapeutic agents. Liver transplantation is effective in many patients and recent experimental studies using adenoviral vectors suggest that gene therapy may ultimately be useful in the treatment of congenital OTC deficiency.
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PMID:Ornithine transcarbamylase deficiency: pathogenesis of the cerebral disorder and new prospects for therapy. 934 66


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