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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

Two cases of tyrosinaemia with eye and skin lesions typical of the Richner-Hanhart syndrome are described. The patients are a 29- and 26-year-old brother and sister. They do not show neurological abnormalities or mental retardation. Parents are not consanguineous and family history is negative for similar conditions. The diagnosis of type II tyrosinaemia was based upon an increase of blood tyrosine (14-16mg/100 ml), tyrosinuria and absence of liver and kidney abnormalities. The treatment with a low tyrosine phenylalanine diet has resulted in a disappearence of the ocular manifestations while the cutaneous lesions are much improved.
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PMID:Familial tyrosinaemia with eye and skin lesions. Presentation of two cases. 2 May 95

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

Tyrosine-induced eye and skin lesions in man are an autosomal, recessive, inherited syndrome associated with tyrosinemia, tyrosinuria, and increased urinary excretion of tyrosine metabolites. Patients have mild to severe keratitis and erosive and hyperkeratotic lesions on the palms and soles. The degree of involvement was variable in the small number of patients studied. Mental retardation is frequently a part of the syndrome. A low-tyrosine low-phenylalanine diet lowers blood tyrosine level and leads to healing of the skin and eye lesions. Early dietary treatment may prevent mental retardation.
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PMID:Tyrosine-induced eye and skin lesions. A treatable genetic disease. 13 41

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

Content of phenylalanine and tyrosine was increased in blood serum in mongolism. When 4 patients with mongolism and 10 healthy persons were loaded with 1-phenylalanine, content of the amino acid in blood serum of patients exceeded 1.5--2-fold that found in healthy persons within 4 and 6 hrs after the treatment. The hydroxylation rate of phenylalanine was lower in mongolism as compared to normal state; it corresponded to the rate of phenylalanine hydroxylation in atypical homo- and heterozygote patients bearing "phenylketonuria" gene and in patients with viral hepatitis. Concentration of tyrosine was distinctly higher in the impaired patients within 2--6 hrs after the loading as compared with the healthy persons. But content of tyrosine was increased only slightly in patients with mongolism during the loading and excretion of homogentisinic acid with urine was decreased. These data suggest that activity of phenylalanine hydroxylase system is impaired in liver tissue in mongolism. Excretion of phenylpyruvic acid with urine was not observed in the patients and healthy persons both before and during the amino acid loading. The data obtained suggest that impairment of phenylalanine and tyrosine turnover in mongolism appears to be one of the factors responsible for disturbance of neurotransmitter synthesis and to be related to development of mental retardation.
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PMID:[Disorders of phenylalanine and tyrosine metabolism in Down's syndrome]. 15 71

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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