Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since many women with phenylketonuria (PKU) will have children of their own, we were interested in ascertaining the effect of maternal PKU and hyperphenylalaninemia on the offspring of such women. We reviewed the literature on this subject and obtained additional unpublished data through an international survey. Data were collected on 524 pregnancies in 155 women; in 34 pregnancies a low-phenylalanine diet was begun after or shortly before pregnancy was established. Among untreated pregnancies, the frequencies of mental retardation, microcephaly, and congenital heart disease were greatly increased over those in the normal population, and these increases correlated with the mother's blood levels of phenylalanine. Ninety-five per cent of mothers with blood phenylalanine concentrations of 20 mg per deciliter or higher had at least one mentally retarded child. Bias introduced by case-finding methods cannot explain these results. It is not clear from our review whether dietary treatment begun after conception is helpful, but treatment begun before conception should be evaluated.
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PMID:Maternal phenylketonuria and hyperphenylalaninemia. An international survey of the outcome of untreated and treated pregnancies. 742 47

During a screening programme of 10000 pregnant women by the Guthrie test, a previously unrecognised phenylketonuric woman was detected. A low phenylalanine diet introduced from the 16th week of gestation failed to prevent fetal abnormality and mental retardation. Maternal phenylketonuria requires earlier diagnosis than can be achieved at the initial antenatal clinic visit if its teratogenic effects are to be prevented.
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PMID:Maternal phenylketonuria: abnormal baby despite low phenylalanine diet during pregnancy. 743 20

To determine the importance of an abnormal EEG in phenylketonuria (PKU), we reviewed 137 EEGs from 48 patients with PKU. Patients were divided into three groups: group 1 (n = 14) had only normal EEGs, group 2 (n = 20) had only abnormal EEGs, and group 3 (n = 14) initially had normal EEGs that later became abnormal. The most common EEG abnormality was focal paroxysmal discharge. Patients in group 2 started treatment at a later age an had a greater frequency of seizures and mental retardation. Phenylalanine levels greater than 20 mg/dL were more often associated with abnormal EEGs. Older patients were more likely to have abnormal EEGs; 78% of the 41 patients who had EEGs at age 6 or older had abnormal records, whereas only 15% of the 26 patients who had EEGs before the age of 6 had abnormal records. Conventionally treated patients with classic PKU and normal EEGs in infancy may have abnormal EEGs when retested later even though they remain on a restricted diet. Although not usually associated with clinical deterioration, abnormal EEGs may unveil the presence of CNS dysfunction even when a child is in satisfactory clinical condition.
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PMID:EEG in phenylketonuria. Attempt to establish clinical importance of EEG changes. 746 35

Child health and life expectancy improved together in many societies in the 20th century. As the incidence of diseases with major extrinsic causes declined, the heritability of disease as a whole increased. Accordingly, the genetic (intrinsic) causes of disease have become important. The genome project is an international venture out of which will come new knowledge about the biological basis of health and disease, and technologies to apply that knowledge in medicine and other disciplines. Phenylketonuria (PKU) at one time was seen only as a rare inborn error of metabolism causing severe mental retardation. Yet, the gene frequency is about 1% in Caucasian and Oriental populations, higher still in some populations with particular histories that have enhanced gene frequency. These genetic facts make PKU a paradigm in human genetics. This genetic disease, for which it was thought there was nothing to be done, has yielded to inquiries at clinical, metabolic, protein (enzyme) and DNA (PAH gene) levels. Results have shown that, early diagnosis (by population screening) and treatment (by low phenylalanine diet) largely prevents mental retardation. DNA analysis reveals particular associations between PKU mutations, RFLP haplotypes and populations; these associations are relevant for counseling. PKU illustrates well how medical science, molecular biology and gene mapping can improve knowledge and contribute to child health.
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PMID:Child health, the genome project and phenylketonuria. 751 3

The history of PKU is one of science in the discovery of an inborn error of metabolism and a chemical cause of mental retardation; and also one of technology with the development of methods to prevent disease. PKU is the classic example of success in the prevention of a genetic disease. Meanwhile, the science has continued to evolve over the 60 years since the discovery of PKU, generating new understanding of its clinical and metabolic phenotypes and about phenylalanine hydroxylation. At least five known genes are involved in hydroxylation of phenylalanine, synthesis of tetrahybrobiopterin and regeneration of this cofactor. The genes have been cloned and mutations characterized for several enzymes (GTPCH, 6-PTPS, PHS/DoCH, DHPR, PAH). A new animal model (the enu mouse) is contributing to knowledge about pathogenesis of brain disease and potential new treatments. The human phenylalanine hydroxylase gene (PAH) itself harbors 99% of the mutations causing hyperphenylalaninemia, over 170 different mutations have been identified at this locus. They cause loss of function; none affecting regulation has been identified. The aggregate PKU gene frequency at 1% is polymorphic in many human populations and mutations are highly stratified by region and population reflecting a variety of mechanisms (founder effect, genetic drift, hypermutability and, perhaps, selection) for their occurrence and distribution.
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PMID:Whatever happened to PKU? 762 72

The objective of neonatal screening for phenylketonuria and congenital hypothyroidism is early diagnosis and initiation of treatment to prevent brain damage and mental retardation. We present the results of the Norwegian national neonatal screening programme for phenylketonuria and congenital hypothyroidism. Screening for phenylketonuria based on serum phenylalanine determinations started in 1967 and covered the whole country in 1978. National screening for congenital hypothyroidism started in 1979. One hundred children with phenylketonuria and 280 children with a strong indication of congenital hypothyroidism have been detected up to 1 October 1994. Screening-related challenges and principles of treatment are discussed.
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PMID:[Screening of newborn infants in Norway for severe metabolic disease]. 790 Jan 9

Maternal phenylketonuria (PKU) has adverse effects on the offspring including microcephaly, mental retardation, congenital heart disease, and intrauterine growth retardation. Maternal non-PKU mild hyperphenylalaninaemia (MHP) is believed to be benign, but whether there may be long-term consequences to offspring is unclear. In an international survey we have obtained information about 86 mothers with MHP (blood phenylalanine 167-715 mumol/L), their 219 untreated pregnancies, and 173 offspring. Spontaneous fetal loss (13% of pregnancies), congenital heart disease (2.3% of offspring), and severe non-cardiac anomalies (2.9% of offspring) occurred at frequencies within expected limits for the general population. For weight and length at birth the median percentile was the 50th but that for birth head circumference was the 25th. Median z-scores for birth length and head circumference were significantly lower for offspring of mothers with phenylalanine concentrations above 400 mumol/L than for those whose mothers had lower values (p = 0.05 and p = 0.005, respectively). The median intelligence quotient (IQ) of the offspring (3-27 years) was 100 for those whose mothers had higher phenylalanine concentrations and 108 for those of the lower phenylalaninaemia group. However, offspring IQ correlated slightly more closely with maternal IQ (r = 0.53, p < 0.001) than with maternal phenylalanine concentration (r = 0.45, p = 0.02). Maternal MHP does not seem to have serious consequences for the fetus. A maternal phenylalanine concentration of less than 400 mumol/L does not warrant intervention. Nevertheless, maternal blood phenylalanine above this value is associated with slightly lower birth measurements and offspring IQ than lower maternal blood phenylalanine concentrations.
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PMID:Maternal mild hyperphenylalaninaemia: an international survey of offspring outcome. 784 32

Phenylketonuria (PKU) is an autosomal recessive genetic disorder caused by phenylalanine hydroxylase (PAH) deficiency. Individuals afflicted with PKU develop irreversible mental retardation that can be largely prevented by the administration of a low-phenylalanine diet. A number of restriction fragment-length polymorphisms (RFLPs) have been identified in the PAH gene. Combinations of RFLPs constitute unique haplotypes that can be used to identify mutant PAH chromosomes for prenatal diagnostic purpose in PKU families. Unfortunately, the utility of haplotype analysis is limited in populations with a single predominant haplotype. We have identified a novel short tandem repeat (STR) within the PAH gene that has an average level of heterozygosity of about 75% in Orientals and about 80% in European Caucasian populations. This single marker is as informative as haplotype analysis in Europeans and nearly twice as informative as haplotype analysis in Orientals. Although there is statistically significant disequilibrium between STR alleles and RFLP-based haplotypes, there is a relatively low degree of disequilibrium between STR alleles and certain RFLP sites. Nevertheless, the combined use of the STR and RFLP haplotype systems increases the informativity of linkage-based tests for prenatal diagnosis and carrier screening in PKU families.
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PMID:A single polymorphic STR system in the human phenylalanine hydroxylase gene permits rapid prenatal diagnosis and carrier screening for phenylketonuria. 810 Jan 64

Maternal phenylketonuria (PKU) is associated with significant complications such as mental retardation, microcephaly and congenital heart defects in nonphenylketonuric offspring. Dietary control with a low phenylalanine diet during the gestation period is effective in improving perinatal outcome in these cases. We present the case of a 27-year-old woman with classical features of PKU who had previously given birth to three babies, all of whom died of congenital heart disease. A low phenylalanine diet was started one month prior to the pregnancy and satisfactory fetal outcome was achieved.
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PMID:Successful management of a pregnancy with maternal phenylketonuria: report of a case. 810 49

Pregnant women who have elevated levels of serum phenylalanine are more likely to have a spontaneous abortion or to give birth to an infant with congenital cardiac anomalies, symmetrical growth retardation, microcephaly and mental retardation than pregnant women with normal levels of this amino acid (1). Nine pregnancies in 7 women were managed in conjunction with the staff of the Children's Hospital, Sydney. In 6 patients, satisfactory serum levels of phenylalanine were attained and 6 offspring are all normal at follow-up, ranging from 15 years to 1 year. The 2 children of the poorly controlled mother were of low birth-weight and both had microcephaly at birth. The poor control of serum phenylalanine was due to poor compliance with the strict dietary regimen. It is concluded that dietary control of serum phenylalanine levels below 600 umol/l in pregnant women with PKU is possible and desirable and may improve perinatal and long-term outcome. This requires close co-operation between paediatrician, dietician, obstetrician and patient. Further data are required to confirm these findings in larger numbers and to provide long-term neurological follow-up.
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PMID:Pregnancy complicated by maternal phenylketonuria. 821 17


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