Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917816 (mental retardation)
 15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three enzymes of purine metabolism, adenylosuccinate synthetase, adenylosuccinate lyase and AMP deaminase, have been proposed to form a functional unit, termed the purine nucleotide cycle. This cycle converts AMP into IMP and reconverts IMP into AMP via adenylosuccinate, thereby producing NH3 and forming fumarate from aspartate. In muscle, the purine nucleotide cycle has been shown to function during intense exercise; the metabolic flux through the cycle has been proposed to play a role in the regeneration of ATP by pulling the adenylate kinase reaction in the direction of formation of ATP, and by providing Krebs cycle intermediates. In kidney, the purine nucleotide cycle was shown to account for the release of NH3 under the normal acid-base status, but not under acidotic conditions. In brain, the purine nucleotide cycle might function under conditions that induce a loss of ATP, and thereby contribute to its recovery. There is no evidence that the purine nucleotide cycle operates in liver. Deficiency of muscle AMP deaminase is an apparently frequent disorder, which might affect approximately 2% of the general population. The observation that it can be found in clinically asymptomatic individuals suggests, paradoxically, that the ATP-regenerating function which has been attributed to the purine nucleotide cycle is not essential for muscle function. Further work should be aimed at identifying the conditions under which AMP deaminase deficiency becomes symptomatic. Adenylosuccinate lyase deficiency provokes psychomotor retardation, often accompanied by autistic features. Its clinical heterogeneity justifies systematic screening in patients with unexplained mental deficiency. Additional studies are required to determine the mechanisms whereby this enzyme defect results in psychomotor retardation.
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PMID:The purine nucleotide cycle and its molecular defects. 152 4

Tuberous sclerosis is a dominant hereditary disease characterized by the appearance of angiofibromas on the face, epileptic attacks, and mental retardation. Attention has been paid to the atypical cells observed histologically in the stroma of the angiofibroma as they may play an important role in forming lesions. We have established a cell line from an angiofibroma to clarify the nature of these cells at the cellular and biochemical levels. The cultured cells have been stably maintained for four years and show an abnormal morphology resembling that of neuronal cells. In culture, these cells divide into daughter cells, which consist of both normal cells and abnormal ones whose nuclei disintegrate and cannot divide further. The cells resemble normal fibroblasts in their pattern of staining with antibodies against tubulin, actin, vimentin, and fibronectin. However, they also stain with an antibody against the glia-specific acidic protein, which is thought to be a specific marker protein for glial cells. The gel profile of cyclic-AMP binding proteins was not fibroblastic, but rather of the neuron cell type. These results indicate the gene expression of these cells is also abnormal. They are a useful tool for understanding this specific genetic disease.
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PMID:Abnormal division and gene expression in cultured cells from a patient with tuberous sclerosis. 260 Feb 65

The inhibition of fetal brain growth resulting from in utero ethanol exposure may impair central nervous system (CNS) development and thereby result in mental retardation. Studies of ethanol-induced brain hypoplasia using chick embryos have shown that the early development of the chick is significantly growth inhibited by a single dose of ethanol (1.0 g/kg) given at the start of incubation (day 0). However, this level of ethanol exposure has been reported to have no effect on chick weight measured at hatching, suggesting that the weights of ethanol-treated chicks were regained during their development. The present experiments were undertaken to determine the biochemical changes associated with the varying growth rates believed to occur in the alcohol-treated embryos. The results indicated that between days 5 and 8 of development, the rates of DNA and protein synthesis (measured as radioactive thymidine and leucine incorporation, respectively) were inhibited by ethanol. The growth inhibition was highly correlated with blood alcohol content and there were associated increases in brain prostaglandin E (PGE) levels relative to vehicle-treated embryos. Further, there was a significant, inverse correlation between brain cyclic AMP content and individual brain weight. By day 10, the ethanol-treated embryos remained smaller than controls but their rates of DNA and protein synthesis were comparable to those of control animals. The normal rates of synthesis observed on day 10 appeared to correlate with clearance of the ethanol dose and with restoration of normal brain levels of PGE relative to 10-day vehicle-dosed embryos.
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PMID:Brain growth during ethanol-induced hypoplasia. 283 89

Recently numerous reports show deleterious effects of alcohol abuse on pregnant women giving their children a high risk of stillbirth and/or several developmental abnormalities and mental retardation, i.e. the Fetal alcohol syndrome (FAS). In the present study, the effects of maternal alcohol consumption on lipid metabolism in the litter liver were investigated in rats. These rats showed not only quite less lipid deposition in spite of large amount of alcohol consumption up to adulthood, but also showed increased FFA oxidation in the livers. In addition, increased level of very low density lipoprotein and hypoglucagonemia were found. 40 micrograms/kg of glucagon which is known as an inhibitory factor of apoprotein production in the liver, was injected for 2 weeks into the rat tail vein and resulted in apparent fatty liver and hypolipoproteinemia. Norepinephrine injection (1 mg/kg) caused plasma glucagon to be depressed in the rat as compared with adult alcohol rats. Plasma cyclic AMP response to glucagon was also depressed in these rats. From these results, it is suggested that the deranged glucagon secretion from the pancreas and lowered glucagon-induced cyclic AMP response would relate to the abnormal lipoprotein metabolism in the rat.
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PMID:[Experimental studies on lipoprotein metabolism in rats reared with liquid alcohol diet from the fetal life]. 298 81

Retarded fetal brain growth is associated with a high incidence of mental retardation among the offspring of chronic alcoholic mothers. Research using an embryonic chick model suggests that ethanol exposure suppresses fetal development including suppression of brain growth. Total brain cyclic AMP content and endogenous brain protein kinase specific activity are not altered by ethanol; however, ethanol exposure does significantly stimulate kinase catalytic activity measured in the presence of saturating amounts of exogenous cyclic AMP.
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PMID:Ethanol-induced inhibition of chick brain growth. 609 89

A 16-year old girl of short stature, with round face, mental retardation, and Albright's dimple sign was admitted for evaluation of hypocalcemia. Her serum calcium levels were 6.3-8.0 mg/dl, and phosphorus 6.9-7.8 mg/dl. Although a diagnosis of pseudohypoparathyroidism was initially suggested, her serum iPTH concentration was low (0.1 ng/ml). Furthermore, an injection of synthetic human parathyroid hormone (100 U, hPTH (1-34] was followed by a marked increase in urinary excretion of cyclic AMP and phosphorus. This case suggests that a shortened metacarpal is not a reliable guide in distinguishing between idiopathic hypoparathyroidism and pseudohypoparathyroidism and that a standard Ellsworth-Howard test is a prerequisite to differential diagnosis.
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PMID:A patient of short stature with idiopathic hypoparathyroidism round face and metacarpal signs. 609 68

Three cases of pseudohypoparathyroidism with roentgenographic evidence of hyperparathyroid bone disease are described. Renal resistance to exogenous parathyroid hormone (PTH), the hallmark of pseudohypoparathyroidism, was documented by markedly blunted or absent urinary phosphate and cyclic AMP responses to parathyroid extract. At the time of diagnosis all patients were hypocalcemic and hyperphosphatemic with elevated serum alkaline phosphatase levels and subperiosteal resorption noted on skeletal films. Bone biopsy in one patient revealed a histologic appearance consistent with hyperparathyroidism. Serum PTH levels, measured in two patients while they were hypocalcemic, were elevated. None of the patients had short stature, brachydactyly, subcutaneous calcification or mental deficiency. These cases are compared to the 15 well-documented cases previously reported. The presently available information on pseudohypoparathyroidism indicates a variable skeletal response to PTH mediated by several factors extrinsic to bone and suggests that pseudohypoparathyroidism with hyperparathyroid bone disease is one extreme of a clinical spectrum of skeletal responsiveness to PTH. This disorder is part of an expanding clinical picture which makes pseudohypoparathyroidism a diagnostic consideration in any patient with unexplained hypocalcemia, hyperphosphatemia, elevated alkaline phosphatase levels or metabolic bone disease.
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PMID:Skeletal responsiveness in pseudohypoparathyroidism. A spectrum of clinical disease. 624

Determinations were made of the plasma cyclic AM level to examine its relationship with hyperkinesis (Werry-Weiss-Peters Activity Scale, WWPAS) and other features of mental disorders in 80 children, of whom 21 had early infantile autism, 15 hyperkinetic mental retardation, 12 minimal brain dysfunction and 32 Down's syndrome. In autistic and hyperkinetic mentally retarded children, the plasma cyclic AMP levels were higher than in normal children and were positively correlated with the WWPAS score. In children with minimal brain dysfunction, the plasma cyclic AMP level was significantly lower than in normal children and was not correlated with the WWPAS score. In children with Down's syndrome, the plasma cyclic AMP level was somewhat higher than in normal children.
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PMID:Plasma cyclic AMP level in psychiatric diseases of childhood. 624 42

The Rubinstein-Taybi syndrome (RTS) is a well-defined syndrome with facial abnormalities, broad thumbs, broad big toes and mental retardation as the main clinical features. Many patients with RTS have been shown to have breakpoints in, and microdeletions of, chromosome 16p13.3 (refs 4-8). Here we report that all these breakpoints are restricted to a region that contains the gene for the human CREB binding protein (CBP), a nuclear protein participating as a co-activator in cyclic-AMP-regulated gene expression. We show that RTS results not only from gross chromosomal rearrangements of chromosome 16p, but also from point mutations in the CBP gene itself. Because the patients are heterozygous for the mutations, we propose that the loss of one functional copy of the CBP gene underlies the developmental abnormalities in RTS and possibly the propensity for malignancy.
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PMID:Rubinstein-Taybi syndrome caused by mutations in the transcriptional co-activator CBP. 763 Mar 90

Among 201 patients diagnosed with HAM/TSP at Kagoshima University, 21 juvenile onset patients had manifested clinical signs and symptoms at less than 15 years of age. They appeared to have common characteristics such as short stature and slight mental retardation. These signs prompted us to investigate five of them endocrinologically; and three patients with pseudohypoparathyroidism (PHP) were confirmed. Serum calcium levels were low, and human parathyroid hormone (PTH) infusion (Ellsworth-Howard test) caused low response in urinary cyclic AMP and phosphorus excretion. The first case had IgA nephropathy, which is generally associated with infectious diseases, while the second case had muscular lymphocytic infiltration. The mothers of cases 1 and 2, who were both seropositive for HTLV-I, were suspected to have abnormal calcium metabolism based on Ellsworth-Howard test. A brother of case 1 and two sisters of case 3 had also HAM/TSP and short stature. The early clinical onset of HAM/TSP may be due to PTH receptor anomaly and a low level of 1,25-dihydroxyvitamin D, which is deficient in PHP and is involved in the regulation of the immune response. The association with IgA nephropathy or myositis may result from progressive HTLV-I infection.
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PMID:Three cases of juvenile onset HTLV-I-associated myelopathy with pseudohypoparathyroidism. 822 62


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