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

The case of a three-year-old boy with mental retardation, moderate muscular hypotony and speech delay is presented. The mild form of maple syrup urine disease was suspected at the first blood screening test by means of ion-exchange thin-layer chromatography. The diagnosis was confirmed by quantitative serum amino acid analysis and protein loading. On a low protein (2 g/kg body weight) diet completed with leucine-isoleucine-valine free formula prompt and lasting normalization of the serum amino acid level ensued with steady improvement of the clinical and neurological status.
 ...
PMID:Mild variant of maple syrup urine disease. 70 84

Two siblings who were repeatedly admitted to hospital with acute episodes of vomiting, dehydration and coma were found to be suffering from isovaleric acidaemia. This condition is a rare inherited abnormality of leucine metabolism, which is frequently fatal in the early weeks of life and leads to mental retardation in a high proportion of those who survive early attacts. However, both our patients were of normal intelligence. The clinical presentation, biochemical defect, diagnosis and suggested therapies are reviewed.
 ...
PMID:Isovaleric acidaemia in two South African children. 88 34

1. The pathogenesis of the mental retardation in phenylketonuria remains obscure. Leucocytes have proved of value in the study of other inborn errors of metabolism. The lymphocyte is a suitable model cell for the study of mammalian metabolism, because of its ability to divide in vitro in response to various stimuli. 2. We have examined the effects of phenylalanine, phenylpyruvate, phenyl-lactate and phenylacetate on the human leucocyte and the resting and phytohaemagglutinin-stimulated rabbit lymphocyte. 3. Phenylpyruvate and phenyl-lactate reduced acetate incorporation into leucocyte lipid by 38% and 48% respectively. Only phenyl-lactate reduced acetate incorporation into the resting and stimulated lymphocyte, by 20% and 34% respectively. 4. Glucose incorporation into leucocyte lipid was unaffected by phenylalanine, phenylpyruvate and phenyl-lactate. Only phenyl-lactate inhibited (46%) the production of CO2 from glucose. 5. Phenylalanine and leucine incorporation into trichloroacetic acid-insoluble material of resting and stimulated lymphocytes was inhibited by phenyl-lactate (10-42%), phenylpyruvate (27-57%) and phenylacetate (19-39%). 6. Uridine incorporation into resting and stimulated cells was inhibited by phenyl-lactate (22-26%), phenylpyruvate (42-52%) and phenylacetate (20%). 7. Thymidine incorporation into resting lymphocytes was reduced by phenyl-lactate, phenylpyruvate, phenylacetate and phenylalanine by 12-26%. Incorporation into the stimulated cell was inhibited by phenylpyruvate and phenyl-lactate (90%) and phenylacetate (66%). 8. Phenylalanine inhibited lymphocyte pyruvate kinase and phenylpyruvate inhibited citrate synthetase. 9. These results are compared with published data relating to experimental hyperphenylalaninaemia and the effects of these metabolites on nervous tissue in vitro.
 ...
PMID:Effect of phenylalanine and its metabolites on the metabolism of leucocytes and lymphocytes. 123 28

We describe the molecular characterization of two mutations responsible for galactosemia, an inherited disorder of galatose metabolism that causes jaundice, cataracts, and mental retardation in humans. The coding region of galactose-1-phosphate uridylyltransferase (GALT; UDPglucose:alpha-D-galactose-1-phosphate uridylyltransferase, EC 2.7.7.12) was amplified by the polymerase chain reaction from total cDNA of a classic galactosemic individual and was characterized by direct sequencing of the products. Two missense mutations were identified: (i) replacement of valine-44 by methionine and (ii) replacement of methionine-142 by lysine. These mutations led to a drastic reduction in GALT activity when individual mutant cDNAs were overexpressed in a mammalian cell system, although full-length protein is synthesized in this assay. The two galactosemia mutations account for 3 of the 15 galactosemia alleles analyzed. These results suggest that galactosemia is caused by a variety of mutations, which might be responsible for the observed clinical heterogeneity of this disorder. We also present the molecular characterization of two GALT polymorphisms: (i) replacement of leucine-62 by methionine and (ii) replacement of asparagine-314 by aspartate. It appears that galactosemia mutations tend to occur in regions that are highly conserved throughout evolution while the polymorphisms change variable residues.
 ...
PMID:Molecular basis of galactosemia: mutations and polymorphisms in the gene encoding human galactose-1-phosphate uridylyltransferase. 201 74

The transport of the eight amino acids (phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, histidine and methionine) using the large neutral amino acid transporter of the blood-brain barrier (BBB) has been calculated using published kinetic data. The fate of the amino acids has been followed from blood to interstitial space, to cell and through metabolism which included, for tyrosine and tryptophan, the hydroxylases. The system was analysed in terms of flux control coefficients. Since the summation theorem did not hold, the system clearly behaved as a non-homogeneous system. At physiological levels of these eight amino acids, the largest contribution to the control of the flux of tyrosine is given by the hydroxylase step, followed by the diffusional component of the transport across the BBB. For tryptophan it is the hydroxylase step, followed by the carrier-mediated transport across the BBB. For the other amino acids it is the metabolism, followed by the diffusional component of the BBB transport. These parameters for tyrosine and tryptophan were determined at increased levels of blood phenylalanine, tyrosine or histidine. The flux through tryptophan hydroxylase can be affected by high blood levels of tyrosine and histidine to values also observed in hyperphenylalaninaemia. Since hypertyrosinaemia (type II) and hyperhistidinaemia are not associated with mental retardation, it is concluded that interference with transport across the BBB of tyrosine and tryptophan, as well as the flux through tryptophan hydroxylase leading to the synthesis of 5-hydroxytryptamine, do not contribute to the cause of permanent brain dysfunction in hyperphenylalaninaemia. It can be calculated that addition of tyrosine to the diet to raise the blood tyrosine level in phenylketonuria patients may have a beneficial effect for the synthesis of neurotransmitters derived from tyrosine.
 ...
PMID:The control of 5-hydroxytryptamine and dopamine synthesis in the brain: a theoretical approach. 210 47

A girl suffering from marked muscular hypotonia, severe statomotor and mental retardation, bilateral optic atrophy with chorioretinal degeneration, convulsions and a moderate compensated metabolic acidosis is described. Screening for metabolic disorders revealed massive 3-methylglutaconic with 3-methylglutaric aciduria leading to the tentative diagnosis of 3-methylglutaconyl-CoA hydratase deficiency. Metabolite excretion was correlated with variation of leucine intake. 3-methyl-3-hydroxyglutaryl-CoA lyase activity in cultured fibroblasts was normal. The suspected metabolic defect was not demonstrable in cultured skin fibroblasts, however.
 ...
PMID:3-Methylglutaconic and 3-methylglutaric aciduria in a patient with suspected 3-methylglutaconyl-CoA hydratase deficiency. 258 Jul 10

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.
 ...
PMID:Brain growth during ethanol-induced hypoplasia. 283 89

Pregnant rats were loaded with L-phenylalanine, and the distributions of [14C]leucine and [14C]urea into fetal plasma and tissues were examined. Uptake of [14C]leucine into the supernatant and protein fractions of fetal plasma and tissues was low in the rats loaded with phenylalanine. In contrast, [14C]urea was distributed identically in both groups, indicating that maternal hyperphenylalaninemia did not affect blood flow across the placenta. Administration of phenylalanine and p-chlorophenylalanine produced amino acid imbalance in fetal tissues. Along with these changes, polysomes of the affected fetal heart and brain disaggregated without changes in the ribonuclease activity. These results indicate that high phenylalanine levels in maternal plasma disturb the active transport of amino acids across the placenta, causing an amino acid imbalance and disaggregation of polysomes in fetal heart and brain. These changes may contribute to the congenital heart disease and mental retardation of maternal phenylketonuria.
 ...
PMID:Effects of phenylalanine loading on protein synthesis in the fetal heart and brain of rat: an experimental approach to maternal phenylketonuria. 294 18

Nine patients with isovaleric acidemia were treated with a low-protein diet and supplemental glycine for up to 10 years. Carnitine was added to the therapy in four patients. Overall, the treatment was well tolerated, resulting in no significant side effects other than persistent hyperglycinemia. Normal growth was observed in all patients. Of four patients with the chronic phenotype, three, whose treatment was delayed beyond the first year of life, are mentally retarded. Two of five patients with the acute phenotype are retarded. The outcome in these two was complicated in one by neonatal intraventricular hemorrhage and in the other by therapeutic noncompliance. In our patients, only those who were treated successfully from early infancy and had no complications did not develop mental retardation. After initiation of therapy, there was a significant decrease in ketoacidotic attacks requiring hospitalization. Glycine is indicated for the treatment of acute ketoacidosis in these patients; none of the catastrophically ill newborn who received glycine died. The aim of treatment is to reduce the isovaleric acid burden to a minimum. Therapy consisting of leucine restriction with supplemental glycine and carniline should be started as soon as possible after birth.
 ...
PMID:Isovaleric acidemia: medical and neurodevelopmental effects of long-term therapy. 338 30

To clarify the effects of perinatal anoxia on the subsequent amino acid metabolism in the brain of children, free amino acid levels in the cerebrospinal fluid (CSF) were determined in 15 children diagnosed as having cerebral palsy and/or mental retardation with perinatal anoxia, and 58 control children without anoxia, aged from 4 days to 12 yrs. There was no significant difference in total amino acid levels between anoxic children and the controls. In the controls, the Gln level in CSF was high, Arg, Asp and Glu levels in CSF were almost the same during infancy and childhood, and the levels of Orn, Lys, His, Tau, Thr, Ser, Asn, Gly, Ala, Val, Met, Ile, Leu, Tyr and Phe in CSF decreased with age until pre-school age. In the newborns and infants among the anoxic children, the levels of most free amino acids in CSF were relatively high compared with those of the controls and, except Glu and Gln, decreased with age during infancy. The Orn, His, Gly, Tyr and Phe levels in CSF of anoxic children were lower than those of the controls in older infants. These results suggest that perinatal anoxia affected free amino acid patterns in CSF of newborns and infants and that the subsequent disturbance of amino acid metabolism in their brains remained after birth.
 ...
PMID:The effect of perinatal anoxia on amino acid metabolism in the developing brain. Part II: The effect of perinatal anoxia on the free amino acid patterns in CSF of infants and children. 406 76


1 2 3 4 5 Next >>