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)

Nutritional approaches are available for the management of several different classes of inborn metabolism errors. In phenylketonuria (PKU), phenylalanine is not properly metabolized; and its accumulation leads to neurologic dysfunction and metal retardation. Altering the diet to limit phenylalanine intake led to remarkable improvement in children with PKU. It was later found that instituting dietary therapy immediately after identification of the disorder in newborns prevented mental retardation. Throughout the 1960s nutritional therapies were found for other inborn disorders, including galactosemia, maple syrup urine disease, and homocystinuria. For the group of disorders associated with defects in the urea cycle, leading to profound hyperammonemia, therapy based on the concept of waste nitrogen excretion (i.e., by increasing excretion of urea cycle intermediates in the urine, nitrogen that would otherwise recycle as ammonia can be eliminated) dramatically produced better control of hyperammonemia and its consequences. Some inborn errors of metabolism respond to vitamin therapy. Biotin-related multiple carboxylase synthetase deficiency can be produced by either of two enzyme defects--holocarboxylase synthetase deficiency or biotinidase deficiency. Both are treatable with biotin supplementation. The symptoms of multiple carboxylase deficiency can also occur after intestinal resection or ingestion of raw eggs. Multiple carboxylase deficiency has been treated successfully in utero by giving the mother biotin supplements. Peroxisomal disorders may respond to dietary management. Liver disease in hereditary tyrosinemia may be accentuated by hypermethioninemia and treated by controlling the blood methionine level. Glycogen storage disease Type I, which causes hypoglycemia, can be controlled by oral administration of cornstarch.
 ...
PMID:Nutritional therapy for selected inborn errors of metabolism. 268 28

Five-hundred and fifty one mentally retarded children from seven institutes in Northern Taiwan were screened by dried blood spot for the detection of treatable congenital metabolic diseases, including congenital hypothyroidism, phenylketonuria, homocystinuria, maple syrup urine disease and galactosemia. We found 2 children (0.36%) with congenital hypothyroidism, 1 case (0.18%) of classical phenylketonuria and two cases (0.36%) of trisomy 21 associated with autoimmune thyroiditis. The results of our investigation suggest that congenital hypothyroidism and phenylketonuria can be the factors causing mental retardation among children in Taiwan and mass neonatal screening of these treatable inborn metabolic diseases is strongly indicated for efficiently circumventing mental retardation in our community.
 ...
PMID:Screening of congenital hypothyroidism, phenylketonuria, galactosemia, homocystinuria, and maple syrup urine disease in moderate to severe mentally retarded Chinese children. 278 33

The low-calorie sweetening agent, aspartame, is broken down in the small intestine into three moieties: aspartic acid, methanol and phenylalanine. Acute loading studies have been performed in human beings who received up to six times the 99th percentile of the projected daily intake (6 X 34 = 200 mg/kg). No evidence of risk to the fetus was developed. Aspartate does not readily cross the placenta. Small elevations of blood methanol following such abuse doses of aspartame did not lead to measurable increases of blood formic acid, which is the product responsible for the acidosis and ocular toxicity in methanol poisoning. Phenylalanine is concentrated on the fetal side of the placenta. Aspartame in abuse doses up to 200 mg/kg in normal subjects, or to 100 mg/kg in PKU heterozygotes, did not raise blood phenylalanine levels to the range generally accepted to be associated with mental retardation in the offspring. It is concluded that, under foreseeable conditions of use, aspartame poses no risk for use in pregnancy.
 ...
PMID:Use of aspartame in pregnancy. 286 25

The reduction of working ability, because of disease, was considered in 1,053 subjects. 21 groups of maladies were found; the neurological disease and mental retardation (MR) caused various degrees of working inability in 416 subjects, i.e. in the 39.51% of the examined population; orthopaedic changes affected the 15.57% of the patients; psychic disorders determined some inability in 8.93% of the persons. The subjects unable to work receive, by Law, an economic help. This study was limited to neurological patients and to subjects mentally retarded. The working ability was reduced by 5 types of disturbances: neuromotor pathology, mental retardation, mental deterioration and dementia, epilepsy, other neurological diseases. The neuromotor pathology affected 163 subjects; the types of symptomatology: hemiplegia; it was found in 71 patients; 62 times it was the result of cerebrovascular disease; in 4 patients it was caused by a hypoxic-ischaemic pre-perinatal encephalopathy. 43 patients affected by cerebrovascular disease lost their personal autonomy, i.e. they could no longer do the activities of daily living (ADL); 7 patients lost their working ability; 12 subjects kept some ability to work. The hemiplegias which struck after 50 years of age were caused by cerebrovascular disease; paraplegia: 28 paraplegic patients have been seen; the aetiology was: poliomyelitis in 8 subjects; MS in 5 patients; ALS in 2 patients; in 13 patients the aetiology was unknown. 6 patients resulted unable to work; 8 persons kept some working ability; 14 patients lost the ability to do the ADL; tetraplegia, or double/bilateral hemiplegia, was found in 20 patients; the aetiology: poliomyelitis in 4 patients; pre-perinatal hypoxic ischaemic encephalopathy in 4 patients; 3 patients of MS; lesion of the cervical spinal cord because of breech delivery in 2 patients; the aetiology was not known in 7 persons. The ability to do the ADL was lost in 17 patients; 3 subjects kept some working ability. Double or bilateral hemiplegia (Little disease) was the model of neuromotor deficit subsequent natal encephalopathy (Infantile Cerebral Palsy, PCI); brachial plexus paralysis was only found from obstetrical (i.e. natal) origin; poliomyelitis and PKU resulted prevented as of 10 years. Mental Retardation (MR) was considered a borderline pathology between neurology and psychiatry; it included 162 subjects: in patients with severe MR a pre-perinatal hypoxic-ischaemic encephalopathy was found in 40.4% of the cases; in patients affected by moderate or light MR the same encephalopathy was found in the 11.3% of the subjects.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Neurologic diseases, mental retardation and reduction in work capacity]. 293 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

We have recently shown that cytoplasmic malate dehydrogenase (MDH-s) from several non-human species catalyses the reduction of aromatic alpha-keto acids in the presence of NADH (Friedrich et al. 1987), an activity previously attributed to the enzyme aromatic alpha-keto acid reductase (KAR E.C.1.1.1.96). Here we present evidence that this also occurs in humans, and that the previously characterized human KAR is not the product of a genetically distinct locus. Human MDH-s and KAR activities co-migrate after starch gel electrophoresis, and electrophoretic variants of human MDH-s exhibited identical variation for KAR. Both enzymes show almost no electrophoretic variation among human populations of diverse origin. The reduction of aromatic alpha-keto acids is substantially inhibited by malate, the end-product of the MDH reaction. Antibodies raised against purified chicken MDH-s equally inhibited both MDH-s and KAR in chickens and humans. The bulk of the KAR activity in human blood appears to be due to MDH-s, with a minor fraction catalysed by LDH, as is the case in most other species studied. The previous assignment of a gene for KAR to human chromosome 12 in human/Chinese hamster somatic cell hybrids is questioned because interspecific hybrid bands of both MDH-s and LDH appear with slightly different mobility approximately midway between the human and hamster controls in somatic cell hybrid studies, and the meaning of this artifact is discussed. The discovery that MDH reacts with intermediate metabolites of phenylalanine and tyrosine has implications in relation to the mechanism by which mental retardation may be produced in phenylketonuria (PKU), and the effect of MDH inhibition on oxidative phosphorylation in the various tyrosinaemias is discussed.
 ...
PMID:Biochemical and genetic identity of alpha-keto acid reductase and cytoplasmic malate dehydrogenase from human erythrocytes. 305 44

Current data indicate that Rett syndrome is an important contributor to the total burden of idiopathic mental retardation. Studies from Sweden suggest that among girls the prevalence of Rett syndrome may be twice the prevalence of phenylketonuria. Successful epidemiologic studies of idiopathic mental retardation syndromes will require both large sample sizes and homogeneous populations. Because Rett syndrome is a relatively homogeneous and common syndrome of idiopathic mental retardation, epidemiologic methods may be more productive in the study of Rett syndrome than in other syndromes of mental retardation that are less clinically homogeneous. The approaches used in studying Rett syndrome epidemiologically may later be useful in the study of other syndromes of idiopathic mental retardation.
 ...
PMID:The epidemiology and public health significance of Rett syndrome. 305 84

Pregnant women with untreated phenylketonuria (PKU) with blood phenylalanine levels greater than 1200 mumol/L usually give birth to offspring with congenital birth defects, including microcephaly, cardiac defects and mental retardation. According to Mabry and Levy, hyperphenylalaninaemic (HPA) women with blood phenylalanine levels between 600 and 1200 mumol/L also have an increased risk to their offspring. To study this problem further, the National Institute of Child Health and Human Development has established a collaborative study for 7 years to elucidate a proper treatment programme for these women.
 ...
PMID:Maternal phenylketonuria. 309 85

The screening of neonates for metabolic diseases is important in order to identify a population with or at risk for metabolic diseases. Early diagnosis can then be made, treatment instituted and physical and/or mental handicaps due to the disease can be prevented. The World Health Organization's screening criteria are helpful in selecting those diseases appropriate for screening. Usually a state-designated central laboratory performs the screening tests. All states screen for phenylketonuria (PKU) and hypothyroidism; in addition, 26 states screen for galactosemia, 20 for maple syrup urine disease and 19 for homocystinuria. The cost-benefit ratio for screening programs is excellent, varying from 1:13 to 1:20. The necessary follow-up of patients for diagnosis and treatment can be enhanced by maintaining a close liaison with the laboratory and providing adequate information to parents. As a result of instituting a screening program, the incidence of mental retardation due to PKU has been practically eliminated and new insights about metabolic diseases have been obtained. The rapid progress in technology may soon result in better and cheaper tests capable of identifying more diseases amenable to treatment.
 ...
PMID:Neonatal screening for metabolic and endocrine diseases. 311 77

The authors report their experience in the systematic, co-ordinated and controlled neonatal screening in France: a coverage of approximately 100 per cent for several years, nearly 13 millions of tests for phenylketonuria and more than 7 millions for hypothyroidism, almost 850 phenylketonuric children and more than 1,600 patients with hypothyroidism, screened and taken care of. The frequency of phenylketonuria is estimated at 1 for 16,394 and the frequency of hypothyroidism at 1 for 4,041. They insist on the need for a strict investigation of false negatives and point out a few specific points on the care of affected children. Overall, the assessment of neonatal screening is positive since it has allowed 2,500 children, doomed to mental retardation, to have a normal growth.
 ...
PMID:[Neonatal screening for phenylketonuria and hypothyroidism in France. A 12-year experience]. 317 78


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