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

Four women with classic phenylketonuria (blood phenylalanine greater than 1200 mumol/L) were given a phenylalanine-restricted diet; three also received L-tyrosine supplements. Biochemical measures of nutrition were normal except for iron deficiency anemia, and in one woman folate deficiency. One pregnancy in which treatment began before conception and another treated from 8 weeks gestation, both with blood phenylalanine levels maintained at 120 to 730 mumol/L, resulted in normal newborn infants whose postnatal growth and development have also been normal. A third pregnancy, treated from 6 gestational weeks, was marked by poor dietary compliance until the middle of the second trimester; fetal microcephaly was identified by ultrasonography at 28 weeks but not at 21 weeks. The child has microcephaly and motor delay. The fourth pregnancy, not treated until the third trimester, produced a child with microcephaly, mental retardation, hyperactivity, and neurologic deficits. It is likely that fetal damage from maternal phenylketonuria can be largely and perhaps entirely prevented by dietary therapy, but therapy must begin before conception for the best chance of a normal infant.
 ...
PMID:New England Maternal PKU Project: prospective study of untreated and treated pregnancies and their outcomes. 381 40

Phenylketonuria provides a human model for the study of the effect of phenylalanine on brain function. Although irreversible mental retardation is preventable through newborn diagnosis and dietary phenylalanine restriction, controversy exists regarding the effects of increased concentrations of phenylalanine in older patients. We have studied ten older, treated, phenylketonuric patients using a triple-blind, multiple trials, crossover design. Each patient was tested at the end of each of three 1-wk periods of high or low phenylalanine intakes. Tests included a repeatable battery of neuropsychological tests, analysis of plasma amino acids, and measurement of urine amino acids, phenyl organic acids, dopamine, and serotonin. In all 10 patients plasma phenylalanine rose (900-4,000 microM). In 9 of 10 patients there was an inverse relationship between plasma phenylalanine and urine dopamine excretion. When blood phenylalanine was elevated, these patients had prolonged performance times on neuropsychological tests of higher but not lower integrative function. Urinary serotonin fell during phenylalanine loading in six patients. The concentration of phenylacids in the urine was not proportional to the plasma phenylalanine at concentrations below 1.5 mM. In one patient, neither performance time nor dopamine excretion varied as blood phenylalanine rose or fell. We interpret these data as follows: blood phenylalanine above 1.3 mM impairs performance on neuropsychological tests of higher integrative function, this effect is reversible, and one mechanism may involve impaired biogenic amine synthesis.
 ...
PMID:Biochemical and neuropsychological effects of elevated plasma phenylalanine in patients with treated phenylketonuria. A model for the study of phenylalanine and brain function in man. 388 Jul 75

The metabolites of phenylalanine, phenylacetate, phenyllactate, phenylpyruvate and phenylethylamine, were measured in the urine of PKU patients. In general correlation was found between serum phenylalanine excretion of these metabolites. However, there were individual variations in the quantities and type of metabolites excreted that could not be explained by blood phenylalanine levels. In a PKU pregnancy large quantities of phenylalanine metabolites were found in urine despite a modest elevation of serum phenylalanine. Increase in the excretion of phenylalanine metabolites was found in patients who were considered to have good blood phenylalanine control. These preliminary studies indicate that the current practice of allowing a wide range of blood phenylalanine in the treatment of PKU may have to be reexamined. Since these metabolites are neurotoxic, they may afford a new parameter for the study of PKU not only regarding the prevention of mental retardation but also with regards to behavior and learning disabilities.
 ...
PMID:Phenylalanine metabolites, attention span and hyperactivity. 402 5

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.
 ...
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.
 ...
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.
 ...
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.
 ...
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.
 ...
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."
 ...
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.
 ...
PMID:PKU, learning, and models of mental retardation. 653 25


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>