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

1. Inhibition of the rate of incorporation of [(35)S]methionine into protein by phenylalanine was more effective in 18-day-old than in 8-day-old or adult rat brain. 2. Among the subcellular fractions incorporation of [(35)S]methionine into myelin proteins was most inhibited in 18-day-old rat brain. 3. Transport of [(35)S]methionine and [(14)C]leucine into the brain acid-soluble pool was significantly decreased in 18-day-old rats by phenylalanine (2mg/g body wt.). The decrease of the two amino acids in the acid-soluble pool equalled the inhibition of their rate of incorporation into the protein. 4. Under identical conditions, entry of [(14)C]glycine into the brain acid-soluble pool and incorporation into protein and uptake of [(14)C]acetate into lipid was not affected by phenylalanine. 5. It is proposed that decreased myelin synthesis seen in hyperphenylalaninaemia or phenylketonuria may be due to alteration of the free amino acid pool in the brain during the vulnerable period of brain development. Amyelination may be one of many causes of mental retardation seen in phenylketonuria.
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PMID:Effect of phenylalanine on protein synthesis in the developing rat brain. 546 65

One year's experience with phenylketonuria during the calendar year 1966, the first year for compulsory newborn screening in California, was reviewed. The over-all prevalence rate from reported cases in California during this period was one case per 19,500 persons tested. Fifty-seven persons suspected of having pku were evaluated, and 25 of them were determined to be phenylketonuric. Eleven of the 25 were infants in whom the abnormality was detected through the newborn screening program or because it was detected in a sibling through a screening program. All the newborn phenylketonuric patients were developing normally at the time of last report (although the follow-up periods were short). In nine of the other children, pku was detected because they were retarded. Five retarded children who were diagnosed as phenylketonuric at another clinic were given dietary assistance. Five additional infants had elevated serum phenylalanines but did not have the classic biochemical findings of pku and are being evaluated further. Nine infants with positive screening tests exhibited biochemical and clinical findings consistent with transient tyrosinemia. Eighteen other children were evaluated and found to have no metabolic abnormality. The newborn screening program for pku is of decided benefit in early identification of a group of infants who have a high rate of potentially serious metabolic disease. Early identification permits treatment soon enough to prevent mental retardation. Newly identified patients should be evaluated in a medical setting capable of careful pediatric, biochemical and nutritional surveillance.
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PMID:Phenylketonuria. Experience at one center in the first year of screening in California. 565 55

The offspring of mothers with untreated classic phenylketonuria (PKU) have shown a high frequency of microcephaly, mental retardation, pre- and postnatal growth retardation, and birth defects. The aim of this study was to determine whether phenylalanine (phe) is the teratogenic agent in maternal PKU. To observe the direct effects of phe on organogenesis, embryos of 9.5-day pregnant rats were cultured for 48 h in the presence of phe at concentrations of 0.1 to 6.0 mM. Within this range no morphological abnormalities occurred in exposed embryos, when compared to control embryos. However there was a reduction (P less than or equal to 0.05) in embryonic protein content and somite number at the highest concentration of phe (6.0 mM). This does not preclude the longer-term effects of phe at later stages of gestation. To examine phe transport into the embryo in response to elevated serum phe levels, 3H-phe uptake studies were undertaken. These showed that 3H-phe from the culture serum is incorporated rapidly into the free amino acid pools and embryonic protein. At serum concentrations of 1.4 mM or higher, phe saturation occurs in the cellular pools of the embryo. Amino acid analysis of the exocoelomic fluid showed that when embryos were cultured for 48 h in serum containing 3.45 mM phe, the total amino acid concentration was maintained near the control levels (16 mM). Of this, 27% (4.26 mM) was contributed by phe, and all other amino acids, except methionine, were decreased with respect to control levels.
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PMID:The effects of phenylalanine on cultured rat embryos. 615 Dec 61

The present paper reviews most of the research on mental retardation in Norway, published in 1970-1980. An important part of this work is represented by Hole's reports of experimental phenylketonuria (PKU) in the rat and studies on peptides and protein-associated peptide complexes in mental disturbances, including experimental studies of effects on brain function and behavior of a peptide fraction (factor 3 b 2). Among studies on diseases with mental retardation, are determinations of arylsulphatase A in cultured amniotic fluid cells and in amniotic fluid as measures of prenatal diagnosis of metachromatic leukodystrophy, reports on screening disorders of tyrosine metabolism and the occurrence of positive dye test in blind children and patients with physical and mental handicaps. Further, studies on the effects of antiepileptics on immunoglobulins are reported. In the fields of social medicine, psychology and psychiatry, only few studies have been published in international journals. Brief reports on Norwegian articles comprise studies on work and disability, social and psychological handicaps in special school pupils, psychosis in mental retardation, and some efforts to design psychological treatment programs for the mentally retarded. The majority of research on mental retardation or with relevance to this field in Norway, has either been supported by the Norwegian Council for Research on Mental Retardation, or the Norwegian Research Council for Science and the Humanities. Based on annual reports of these councils, and correspondence to centers involved in such research, we have collected reports published in the period 1970 to 1980. We have also received unpublished reports, but have chosen not to include most of them in this review, because of the difficulties for the readers to obtain these reports. The institutional and noninstitutional services for the mentally retarded in Norway have no formal connection with university or other research institutes. Nevertheless, most of the research papers have been submitted from such institutes. Most of the reports traced are in the fields of basic neurobiology, medicine, and psychology, and will be dealt with under these headings.
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PMID:Research on mental retardation in Norway 1970-1980: a review. 635 79

The Austrian Screening Program examined during 12 years 1,002.424 newborns and uncovered 23 cases of Galactosemia by Transferase deficiency, 6 by Kinase deficiency as well as 1 case of Phosphoglucomutase deficiency, 1 of porto-caval shunt and 1 congenital liver cirrhosis. Among the 23 Transferase deficiencies 18 took a fulminating course and 8 of these died. Since introduction of exchange transfusion as emergency treatment and acceleration of the screening procedure only 2 among 11 have died. Half of all Galactosemia cases, Transferase and Kinase, show already at the first examination (2. week) a cataract which however is reversible. In contrast to Kinase deficiency all cases of Transferase deficiency exhibit mental retardation if they grow older. Since treatment is early (9, 7 days), easy and the IQ already at 4 years 10 points below that of treated PKU's of same age a congenital brain damage has to be considered. Galactosemia by Transferase deficiency is in Western-Austria significantly more frequent than in Eastern-Austria. 17 boys compare with 6 girls. Among 6 cases of Galactosemia by Kinase deficiency 1 belonged to a Gippsy and 2 to Yugoslavian guest worker families. The 23 cases with Transferase deficiency had 45 siblings among whom 11 also were galactosemic. In 8 sibships the clinical course was of the same typ, but in 1 family one child showed the fulminating the other the subacute course.
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PMID:[Hypergalactosemia in newborns as uncovered by the Austrian screening program in 12 years (author's transl)]. 645 54

Factors that relate to reproductive patterns in 129 families after the birth of a child with phenylketonuria (PKU) include birth order of the index child, age of the parents at the birth of the index child, and expressed intentions of the parents whether or not to have additional children. Factors that do not correlate with reproductive histories include knowledge of the genetic and metabolic nature of PKU, the relationship of PKU to mental retardation and special diet, parental upset about the diagnosis, sex of the affected child, parental IQ, religion, education, and social class. Correlations found related to the question, "Is PKU the reason you don't want more children?" include stress factors in family functioning, mother's upset with the diagnosis, father's concerns about being a carrier, sex of the child with PKU, and degree of knowledge about PKU. Many of the Collaborative Study clinics tend to be more concerned about the consequences of PKU on the family than on society, and feel that families should receive genetic counseling to determine their reproductive risks and future plans. Upon self-report, many clinics declare their counseling to be either "completely nondirective" or making a "conscious effort to be nondirective."
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PMID:Impact of PKU on the reproductive patterns in collaborative study families. 650 98

Experimental phenylketonuria was induced in male rats by daily injections of alpha-methylphenylalanine and phenylalanine on postnatal Days 3-31. Beginning at 8 weeks of age, the animals were subjected to a test of observational learning followed by a test of latent learning (two tests of "advantageous" learning). The animals subjected to the PKU treatment early in life showed significant learning deficits in both tests. The importance of these studies lies in the fact that unlike conventional tests of learning, tests of advantageous learning are sensitive to the kinds of biological insults which cause mental retardation in humans. This differential sensitivity evident in studies of animal models of cognitive pathology is analogized to the areas of dysfunction which characterize human mental retardation. Suggestions for the development of appropriate models of intellectual development are made.
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PMID:PKU, learning, and models of mental retardation. 653 25

An increased concentration of dendritic spines was present in one region of the hippocampus in rats made hyperphenylalaninemic (phenylketonuria model). It is uncertain whether this finding resulted from an actual hyperplasia or a failure of maturational spine reduction. The result is unusual in that Golgi studies of most mental retardation syndromes and relevant animal models have shown loss of dendritic spines.
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PMID:Hippocampal dendritic abnormalities in a rat model of phenylketonuria. 654 35

We studied the effects of maternal phenylketonuria and hyperphenylalaninemia on 53 offspring from untreated pregnancies in 22 mothers who were identified by routine screening of umbilical-cord blood. The IQ of the offspring was significantly correlated with both maternal IQ (r = 0.83, P less than 0.001) and maternal blood phenylalanine level (r = 0.82, P less than 0.001), but with one exception, mental retardation in offspring was present only when the maternal blood phenylalanine level exceeded 1100 mumol per liter (18 mg per deciliter). Microcephaly in offspring was consistently present only when the maternal blood phenylalanine level exceeded 1200 mumol per liter (20 mg per deciliter). Congenital heart disease and other congenital anomalies were rare among offspring. The data suggest that severe atypical or classic phenylketonuria (blood phenylalanine level, greater than 1100 mumol per liter) in the mother has a substantial cognitive effect on her offspring but that the effect of mild hyperphenylalaninemia may have been overstated in the past.
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PMID:Effects of untreated maternal phenylketonuria and hyperphenylalaninemia on the fetus. 663 85

Phenylketonuria is an inborn error of metabolism with its most notable characteristic being that of mental retardation. The literature describing this disorder has been reviewed to identify the abnormal lower extremity findings in affected individuals. The dermatologic, osteologic, and neuromuscular systems were all found to be involved. Lower extremity physical examinations were then performed on nine phenylketonuric adults. It was determined that several of the reported manifestations of phenylketonuria were similarly evident in these individuals as well as the presence of additional lower extremity pathology not previously documented. However, the conclusion was made that all findings, past and present, were variable and that no consistent manifestation was apparent.
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PMID:Lower extremity manifestations of phenylketonuria. 664 24


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