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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of phenylalanine and its metabolites (phenylacetate, phenethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) 3-oxo acid CoA-transferase (EC 2.8.3.5) and acetoacetyl-CoA thiolase (EC 2.3.1.9) in brain of suckling rats were investigated. 2. The 3-hydroxybutyrate dehydrogenase from the brain of suckling rats had a Km for 3-hydroxybutyrate of 1.2 mM. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the enzyme activity with Ki values of 0.5, 1.3 and 4.7 mM respectively. 3. The suckling-rat brain 3-oxo acid CoA-transferase activity had a Km for acetoacetate of 0.665 mM and for succinyl (3-carboxypropionyl)-CoA of 0.038 mM. The enzyme was inhibited with respect to acetoacetate by phenylpyruvate (Ki equals 1.3 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). The reaction in the direction of acetoacetate was also inhibited by phenylpyruvate (Ki equals 1.6 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). 4. Phenylpyruvate inhibited with respect to acetoacetyl-CoA both the mitochondrial (Ki equals 3.2 mM) and cytoplasmic (Ki equals 5.2 mM) acetoacetyl-CoA thiolase activities. 5. The results suggest that inhibition of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities may impair ketone-body utilization and hence lipid synthesis in the developing brain. This suggestion is discussed with reference to the pathogenesis of mental retardation in phenylketonuria.
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PMID:Effect of phenylalanine metabolites on the activities of enzymes of ketone-body utilization in brain of suckling rats. 1 50

Urine specimens from 1778 mentally retarded patients and 420 age and sex matched non-retarded controls selected from a general practice have been analysed for non-amino organic acids by a quantitative extraction and gas chromatographic method. The compounds were identified by combined gas chromatography and mass spectrometry. Approximately 5% of the patients had an abnormal organic aciduria. The frequency of abnormalities was slightly higher (about 7%) in a group of 248 severely subnormal children, but not in cases with a family history of mental retardation, retarded sibs, or whose parents were consanguineous. The most frequently observed abnormalities were phenylalanine metabolites in cases of phenylketonuria (about 1%), increased excretion of benzoic acid (about 1%), and increased excretion of 2-oxoglutaric acid with or without raised urinary citric-acid levels (about 1%). The biochemical and clinical significance of these findings is being further investigated.
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PMID:Abnormal organic acidurias in mentally retarded patients. 4 15

Blood-lead concentrations were measured retrospectively in the blood contained on cards used for testing for phenylketonuria in the first two weeks of life. Cards which belonged to 80 of a group of 77 children with mental retardation of unknown aetiology and 77 controls were identified. Of 77 usable cards, 41 were from mentally retarded children and 36 were from controls; 24 mental-retardation/control pairs were found. There was a highly significant trend towards higher blood-lead concentrations in the mentally retarded children. Water-lead concentrations in the maternal home during pregnancy correlated with blood-lead concentrations in the mentally retarded children. These results reinforce the probable association between lead exposure during pregnancy and the development of mental retardation of otherwise unknown aetiology.
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PMID:A retrospective analysis of blood-lead in mentally retarded children. 6 17

Continuing progress has been made in the exploration of the biochemical causes of mental illness. Recent research has indicated that selected abnormalities of specific isoenzymes play an important role in the pathogenesis of heritable metabolic disorders such as phenylketonuria and Niemann-Pick disease. The roles of "animal lectins" and glycosidic enzymes in brain development and synaptogenesis appear to have received important substantiation within the past year. In additions, it has been shown that the blood-brain barrier can be temporarily altered so that exogenous enzymes can enter the central nervous system, and imperative consideration for enzyme replacement therapy in mental disorders. Less satisfactory progress has been made concerining potential anabolic disorders of lipids affecting the nervous system. Finally, novel experimental directions concerning energy metabolism by the brain offer considerable hope for the elucidation of some of the causes of mental retardation.
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PMID:Inherited metabolic diseases and pathogenesis of mental retardation. 10 26

Retarded body and brain growth and a deficit of myelin in the cerebral hemispheres and the cerebellum were observed in an animal model of phenylketonuria, the p-chlorophenylalanine and L-phenylalanine treated preweanling rat. These manifestations of phenylketonuria were reproduced in rats treated with phenylacetate in amounts approximating those likely to be produced in phenylketonuria. Young rats treated with equivalent amounts of other metabolites of phenylalanine, namely, phenylpyruvate, phenyllactate, and mandelate, which also accumulate in the brain during hyperphenylalaninemia, did not exhibit any toxic effects. Phenylpyruvate did not give rise to phenylacetate in the brain, but a small percentage was converted to phenyllactate. The gross composition of myelin isolated from the brains of saline and phenylacetate treated animals was similar. At various time intervals after subcutaneous injection, phenylacetate in the brain reached levels thirty times those of phenylpyruvate and phenyllactate, although animals received equivalent amounts of the three metabolites. The retarded growth of the body and brain of the young animal treated with phenylacetate may be attributed to the formation of phenylacetylcoenzyme A in the tissues. The site of action is very likely linked to acylcoenzyme A metabolism, i.e., the synthesis and utilization of acetylCoA and acetoacetylCoA, which are involved in reactions generating ATP and energy and in the synthesis of cholesterol and fatty acids. Results of this investigation indicate that growth retardation induced by phenylacetate during the period of very rapid development of the brain is responsible for the mental retardation in phenylketonuria.
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PMID:Myelin deficiency in experimental phenylketonuria: contribution of the aromatic acid metabolites of phenylalanine. 15 97

There is increasing recognition that autism is a syndrome, not a disease entity. But it is not yet clear why some children develop autistic behavior more easily than others. It has been noted that autistic symptoms occur more frequently in children with mental retardation, blindness, congenital rubella, phenylketonuria, etc., and that there are very few cases of classical infantile autism in the general population. Very rarely has autism been associated with Down's syndrome. This is a report of a case of Down's syndrome and infantile autism.
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PMID:A case of infantile autism associated with Down's syndrome. 15 85

Low phenylalanine diet treatment in children with phenylketonuria (PKU) started sufficiently early prevents mental retardation. But the question whether the treatment prevents all c n s damage is still open. This problem was evaluated on the basis of longitudinal neurological and psychological studies of 118 PKU children in whom treatment was started before the 6-th week of life. As a comparative group 90 children with untreated or late treated PKU were investigated. A detailed analysis of the results was carried out investigating each case in relation to the precision of dietary restrictions and the duration of treatment. The incidence and type of abnormal findings were compared with the abnormalities found in children with untreated or late treated PKU and with the incidence in the total child population. In 78 children (66,1%) there were no abnormalities in the neurological status and mental development was normal except for some retardation in the visual-motor maturation. In 35 children (29,7%) signs of hyperkinetic syndrome were present in 5 (4,2%) there was both mental retardation and signs of hyperkinetic syndrome. In the comparative group all 90 children had severe neurological abnormalities and mental retardation. The obtained results confirm that the essential effect of the diet on the development of PKU patients is during the first year of life. In order to obtain optimal results however, it is necessary to continue the diet for a sufficiently long period. But in spite of following the prescribed treatment in PKU children it is not always possible to prevent minimal c n s damage.
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PMID:[Neurological status and psychomotor development of children with phenylketonuria treated early]. 26 30

The justification hypothesis postulates that an individual genetically deficient in the synthesis of any of the 12 nonessential amino acids requires that amino acid in the diet just as a normal individual requires any essential amino acid. The deficiency of that single amino acid causes diminished protein synthesis. The hypothesis proposes that mental retardation develops during the late stage of fetal development, when the brain is growing most rapidly, as a result of the inability of the mother to deliver an appropriate amount of that nonessential amino acid to her fetus who, in turn, is unable to correct for this deficiency due to his genetic constitution. A paradigm is provided by the disease phenylketonuria in which the homozygote lacks the enzyme for synthesis of the nonessential amino acid tyrosine. By measuring the appearance of tyrosine in the plasma after an oral dose of phenylalanine, it is possible to show differential capability among siblings of known phenylketonuric children, in the expected Mendelian ratio. The mean IQ of the two-thirds of the siblings who were least able to convert phenylalanine to tyrosine (presumably heterozygotes) was 10 points lower than the mean IQ of the "normals," who were most able to synthesize tyrosine. The difference is statistically significant (P <0.01). The mean maternal IQ was halfway between that of the heterozygote group and that of the normal group, confirming the prediction of maternal-fetal interaction.
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PMID:Diet, genetics, and mental retardation interaction between phenylketonuric heterozygous mother and fetus to produce nonspecific diminution of IQ: evidence in support of the justification hypothesis. 27 41

Microcephaly and considerable motor and mental retardation occurred in two non-phenylketonuric children of an untreated mother with phenylketonuria. The cerebral damage of the children must be considered the consequence of the maternal metabolic disorder. Since the first phenylketonuric children who were treated on strict diet are now reaching the age of marriage and pregnancy, the problem of maternal phenylketonuria is becoming topical. Published reports indicate that of 72 well documented cases with a maternal phenylalanine level above 200 mg/1 (1210 mumol/1) 39 offspring had microcephaly, in 33 intra-uterine growth had been retarded and in 25 there are cerebral palsy and seizures. Almost all had mental retardation. At the same time there have been reports about three normal children whose mothers had kept to a phenylalanine-low diet during their pregnancy.
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PMID:[Children of mothers with phenylketonuria (author's transl)]. 83 53

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.
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PMID:Effect of phenylalanine and its metabolites on the metabolism of leucocytes and lymphocytes. 123 28


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