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)

A Japanese infant was found to have abdominal distension at the age of 4 weeks. A diagnosis of galactosemia was made at 8 weeks of age. Dietary management completely reversed the hepatosplenomegaly and ceased the progression of lens opacities. Mental retardation was also noted at a later age. We believe this is the first reported case of galactose cataract in Japan confirmed enzymatically.
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PMID:Galactose cataract in Japanese patient. 716 3

Galactosemia is an autosomal recessive, inborn error of galactose metabolism due to the deficiency of galactose-I-phosphate uridyl transferase. Late-onset neurologic complications may develop despite Galactose restriction. Three adult patients are reported. They suffered from mental retardation. Two of them developed progressive cerebellar ataxia, spastic gait and postural tremor. The magnetic resonance imaging revealed moderate cortical atrophy, multifocal areas of increased signal in the periventricular white matter on T2-weighted images, and in one case, abnormal myelination. The Fluoro-2-deoxy-D-glucose position emission tomography showed different patterns of regional hypometabolism.
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PMID:[Late neurologic complications of galactosemia: study of 3 cases]. 767 42

Classical galactosemia, which is caused by deficiency of galactose-1-phosphate uridyltransferase, is characterized by acute problems of hepatocellular dysfunction, sepsis, cataracts and failure to thrive. Galactose limitation reverses these symptoms immediately; however, the long-term complications, such as mental retardation and ovarian failures are major problems in most of these patients. In order to investigate the molecular basis for phenotype variation in galactosemia, we have screened the most common mutation in the GALT gene, Q188R. We have further examined those patients who are heterozygous for Q188R or negative for this mutation by SSCP analysis and direct sequencing. In three male patients, we have identified, for the first time, two stop-codon mutations in the GALT gene, G212X (exon 7) and E340X (exon 10). Two patients of 8 and 28 years of age, respectively, who are compound heterozygotes for Q188R and G212X, have severe mental retardation and their general clinical condition is more severe than that of patients with missense mutations. The third patient, who is 8 years of age and who is homozygous for E340X, the N314D polymorphism and a silent substitution L218L, presents with a relatively normal physical and mental condition to date.
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PMID:Characterization of two stop codon mutations in the galactose-1-phosphate uridyltransferase gene of three male galactosemic patients with severe clinical manifestation. 852 34

Classical galactosemia is an inherited metabolic disease that results from galactose-1-phosphate uridyltransferase deficiency. Untreated galactosemia has various manifestations, including central nervous system damage, hepatic failure, cataract. Galactose-restricted dietary treatment, the only therapy used in galactosemia, brings considerable improvement, especially in the neonatal period. However, in the most galactosemic patients this treatment does not prevent development of late-onset complications; mental retardation, ovarian failure and neurologic disturbances. This article presents a review of contemporary hypotheses on possible factors influencing the outcome in galactosemia, especially in regard to late-onset complications.
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PMID:[Galactosemia: a problem still unsolved]. 875 65

The reproductive effects of metabolic disorders in women can be divided into four categories. The first of these is infertility. Galactosemia with its complication of ovarian failure is the disorder in this category. This complication may be prenatal in origin but whether this is so and its cause are unknown. The second category includes pregnancy effects of maternal metabolic disorders. The urea cycle disorder ornithine transcarbamylase (OTC) deficiency, maternal maple syrup urine disease and maternal homocystinuria are in this category. In the first two disorders, postpartum life-threatening illness due to metabolic crisis has occurred. Maternal homocystinuria is associated with a high risk for postpartum thromboembolic complications. The third category is the pregnancy effect of a fetal metabolic disorder. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) have been complicated by the life-threatening (HELLP) syndrome during the third trimester. Rapid recovery of the mothers followed delivery, on occasion by emergency cesarean section. The fourth category is the fetal effects (teratogenicity) from a maternal metabolic disorder. The best-known example of this is maternal phenylketonuria (PKU), which produces microcephaly, mental retardation, congenital heart disease and intrauterine growth retardation. Treatment with a low phenylalanine diet begun before conception or no later than the earliest weeks of the first trimester markedly reduces the risk to the fetus and can result in normal offspring. Other examples of teratogenicity may include maternal homocystinuria and maternal hypothyroidism.
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PMID:Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics. 882 3

Classical galactosemia, characterized clinically by acute hepatic dysfunction, sepsis, cataract, and failure to thrive, is caused by deficiency of galactose-1-phosphate uridyltransferase (GALT). Galactose restriction normalizes these acute symptoms; however, long-term complications such as intellectual deficits and ovarian failure are conspicuous in the majority of patients. Here we report two Turkish siblings with classical galactosemia. The clinical course of the two children differed markedly: only the older girl suffered from severe acute symptoms during the neonatal period, and she developed greater mental retardation than her younger affected brother. The functional activity of GALT was virtually absent in each affected children. The mother and two healthy siblings exhibited approximately 50% normal GALT activity and the father approximately 25%. Molecular analysis revealed that these two galactosemic siblings were homozygous for a stop codon mutation of E340X in GALT exon 10. Moreover, two additional mutations, a neutral polymorphism L218L and N314D, which are typical for the Duarte-I variant, were found in the same GALT allele. The two healthy siblings and the parents were heterozygous for these combinations of mutations. In addition, the father's second GALT allele revealed three intron mutations at nucleotide position 1105 (G-->C), 1323 (G-->A) and 1391 (G-->A) and the N314D mutation, which correspond to the mutations of Duarte-2 variant. Our findings indicate that in classical galactosemia several distinct mutations can be present in one allele (in cis) of the GALT gene. Therefore it seems to be necessary to examine all introns and exons of the GALT gene in galactosemic patients who do not carry the Q188R mutation or another frequent mutation in the GALT gene.
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PMID:Simultaneous occurrence of various mutations and polymorphisms in cis and in trans of the galactose-1-phosphate uridyltransferase gene in a Turkish family with classical galactosemia. 976 50

All 50 states and the District of Columbia conduct newborn screening (NBS) programs that annually screen approximately 4 million infants for metabolic and other disorders to prevent mental retardation, disability, and death. In 1998, Georgia newborns were screened for eight disorders: phenylketonuria, galactosemia, tyrosinemia, homocystinuria, hypothyroidism, maple syrup urine disease, congenital adrenal hyperplasia, and sickle cell disease. Appropriate data that reflect progress toward achieving short- and long-term goals are necessary to assess the effectiveness of NBS and to inform public health policy decisions about which disorders to add or delete from screening. This report summarizes findings from an evaluation of data systems for metabolic and endocrine disorders in the Georgia NBS program and assesses the ability to measure progress toward short- and long-term goals. Although the data indicate that the program typically received specimens of sufficient quality for testing in a timely manner, additional data are needed to assess fully the effectiveness of the NBS program in identifying disorders.
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PMID:Evaluating newborn screening program data systems--Georgia, 1998. 1063 98

India, like other developing countries, is facing an accelerating demographic switch to non-communicable diseases. In the cities congenital malformations and genetic disorders are important causes of morbidity and mortality. Due to the high birth rate in India a very large number of infants with genetic disorders are born every year almost half a million with malformations and 21,000 with Down syndrome. In a multi-centric study on the causes of referral for genetic counselling the top four disorders were repeated abortions (12.4%), identifiable syndromes (12.1%), chromosomal disorders (11.3%) and mental retardation (11%). In a more recent study in a private hospital the top reasons for referral were reproductive genetics (38.9%)--comprising prenatal diagnosis, recurrent abortions, infertility and Torch infections--mental retardation +/- multiple congenital anomalies (16.1%), Down syndrome (9.1%), thalassemia/haemophilia (8.8%), and muscle dystrophy/spinal muscular atrophy (8.4%). The disorders for which prenatal has been done over an 18-month-period are given. A recent study carried out in three centers (Mumbai, Delhi and Baroda) on 94,610 newborns by using a uniform proforma showed a malformation frequency of 2.03%, the commonest malformations are neural tube defects and musculo-skeletal disorders. The frequency of Down syndrome among 94,610 births was 0.87 per 1000, or 1 per 1150. Screening of 112,269 newborns for aminoacid disorders showed four disorders to be the commonest--tyrosinemia, maple syrup urine disease and phenylketonuria. Screening of cases of mental retardation for aminoacid disorders revealed four to be the commonest--hyperglycinemia, homocystinuria, alkaptonuria, and maple syrup urine disease. Metabolic studies of cases of mental retardation in AIIMS, Delhi and KEM Hospital, Mumbai, demonstrated that common disorders were those of mucopolysaccharides, lysosomes, Wilson disease, glycogen storage disease and galactosemia. It is estimated that beta- thalassemia has a frequency at birth of 1:2700, which means that about 9,000 cases of thalassemia major are born every year. Almost 5200 infants with sickle cell disease are born every year. Disorders, which deserve to be screened in the newborn period, are hypothyroidism and G-6-PD deficiency, while screening for aminoacid and other metabolic disorders could presently be restricted to symptomatic infants.
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PMID:Burden of genetic disorders in India. 1126 88

Galactosemia is an autosomal recessive disease related to deficiency of one of three different enzymes involved in the metabolism of galactose: galactokinase (GALK), galactoso-J-phosphate uridyltransferase (GALT) or UDP-galactose-4-epimerase (GALE). Classic galactosemia is due to GALT deficiency and is the most common. Longitudinal studies have shown that in spite of early diagnosis and early treatment of children with galactosemia detected in the mass screening programme, the results are poor and mental retardation as well as other complications are of similar severity as in children diagnosed clinically without screening. In many investigations it was also proved that some impairments developed already in the prenatal period. Therefore, many countries among them also Poland, stopped mass screening for galactosemia. At present, in Poland the procedure strategy in galactosemic children and their families include: diagnosis of new cases on the basis of clinical symptoms, selective screening in high-risk families, prophylactic lactose-free diet for mothers during pregnancy. Such management can help to prevent clinical manifestations in newborns and prevent death in the early period of life.
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PMID:[Effectiveness of the screening programme for galactosemia. New strategy in Poland]. 1127 4

The metabolic and anatomical substrate of most forms of mental retardation is not known. Because the basis of normal brain function is not sufficiently understood, the basis of abnormal function is understood poorly. Even in disorders where the fundamental biochemical defect is known, such as phenylketonuria (PKU) and other enzyme defects, the exact basis for brain dysfunction is uncertain. The outcome for treated PKU, galactosemia, homocystinuria, and lysosomal disorders is not yet optimal. The various forms of nonketotic hyperglycinemia often respond poorly to current therapy. Less familiar disorders, with or without seizures, such as deficient synthesis of serine or creatine and impaired glucose transport into the brain, and disorders with variable malformations, such as Smith-Lemli-Opitz (SLO) syndrome and the congenital disorders of glycosylation (CDGs), may initially be thought to be a nonspecific form of developmental delay. Less familiar disorders, with or without seizures and disorders with variable malformations may initially be thought to be a nonspecific form of developmental delay. Simple tests of urine, blood, and cerebrospinal fluid may lead to a diagnosis, accurate genetic counseling, and better treatment. Metabolic brain imaging (magnetic resonance spectroscopy (MRS)) has also helped to reveal biochemical abnormalities within the brain.
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PMID:Metabolic disorders and mental retardation. 1256 Oct 56


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