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

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

The causes for mental retardation due to perinatal hypothyroidism are not fully understood. Here we show that the most potent component of thyroid hormone, 3,5,3'-triiodo-L-thyronine (T3), selectively increases the density of voltage-activated Na+ currents in hippocampal neurons from newborn rats. Thus, the well known effects of thyroid hormone on energy expenditure and Na+/K+ ATPase activity could to some extent result from the enhanced Na+ influx through voltage-activated Na+ channels. In addition, a down-regulation of the Na+ current density in neurons could contribute to some of the neurological symptoms accompanying hypothyroidism, including slowing of mentation, of neuronal conduction velocities, the alpha rhythm of the electroencephalogram, and increased latencies of evoked potentials and reflexes.
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PMID:Thyroid hormone regulates Na+ currents in cultured hippocampal neurons from postnatal rats. 910 52

Congenital hypothyroidism (CH) is the most common cause of preventable mental retardation. Thyroid hormone deficiency in utero and in the first neonatal months is responsible for permanent damage. While foetal hypothyroidism is at present unavoidable, earlier diagnosis and initiation of treatment in neonates with CH is important and highly recommended. At the moment, the Italian screening program for CH allows diagnosis and treatment within the first month of life. In Italy, screening programs became obligatory only a short time ago. In some regions, they started a few years ago, whereas in others they have been carried out only in an irregular way and only a part of the population has been investigated. Therefore CH was diagnosed just on the basis of clinical signs, with a consequent delay in the initiation of substitutive therapy. We describe the case of a little girl with CH diagnosed when she was three years old. We report the results of this case follow-up study and we describe the features of her neuropsychological development to point out her improvement and permanent disorders. The little girl was clearly hypothyroid with delayed achievement at three, but with pharmacological treatment she showed a dramatic amelioration in growth, language, motor skills and cognitive performances.
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PMID:[Missed diagnosis: a case of congenital hypothyroidism treated after three years]. 913 64

Systematic screening for congenital hypothyroidism in the neonate constitutes a major progress in the prevention of mental retardation, as the condition occurs in 1/4,000 newborns and necessarily results in brain damage if not properly detected and treated during the first days of life. Screening and diagnostic and therapeutic procedures are discussed, as well as outcome and prognosis of the affected infants. Primary thyroid-stimulating hormone screening is almost universally recommended. Early therapy (within 14 days) with appropriate doses of thyroxine (about 10 micrograms/kg/day) will prevent any brain damage even in case of evidence of fetal hypothyroidism, as thyroxine of maternal origin will reach the fetus and largely protect him. Neonatal thyroid screening is also a particularly sensitive monitoring tool in the evaluation of the effects and of the correction of iodine deficiency at the population level.
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PMID:Neonatal screening for congenital hypothyroidism: results and perspectives. 925 21

Endemic cretinism has been classified into neurological and myxedematous types. Profound mental deficiency, deaf-mutism and cerebral diplegia are predominantly found in the former. The latter have been described as less mentally retarded but with severe growth retardation and myxedematous features. The pathogenesis of different clinical types of endemic cretinism is still unclear. Recently, a unifying hypothesis suggested that iodine deficiency, severe enough to cause maternal and fetal hypothyroxinemia, results in neurological defects in all cretins. We conducted the present study in northern Thailand to determine the validity of this hypothesis in another geographical area. The study consisted of a multidisciplinary survey on 112 endemic cretins aged 2-66 years in Nan. They were categorized clinically into three types of endemic cretins, neurological (n = 57), myxedematous (n = 19) and mixed form (n = 36). The subjects were generally short and the majority had severe mental retardation (mean intellectual quotient (I.Q.) 30.8 +/- 8.8), psychomotor defect and profound sensorineural hearing loss. The I.Q. score and proportion of cretins with sensorineural hearing loss and psychomotor defect were similar among the three types of cretins. The most frequent neurological abnormalities were spasticity, hyper-reflexia, the presence of primitive reflexes and gait disturbance. These abnormalities were distributed equally among the three types of endemic cretins. Delayed skeletal maturation and abnormal epiphysis were also present in all types of cretins. However, myxedematous cretins were shorter (P < 0.01), having more myxedematous features (P < 0.05 to P < 0.001) and less sexual maturation (P < 0.05). Thyroid volume was lower in cretins with hypothyroidism (P < 0.01). In conclusion, our findings support the hypothesis that neurological features are present in all types of cretins, and are the consequence of maternal and fetal hypothyroxinemia due to severe iodine deficiency. The clinical manifestations of the cretins were subsequently modified by the length and severity of postnatal iodine deficiency and hypothyroidism.
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PMID:Endemic cretinism in Thailand: a multidisciplinary survey. 936 97

Nineteen cases of duplication of segments of the long arm of chromosome X have been published in 13 males and in 6 females. We report an additional case of a male with growth and mental retardation, growth hormone deficiency, compensated primary hypothyroidism, distinctive anomalies of the face, hypoplastic genitalia, and hypotonia in whom inverted duplication of a segment in the long arm of X chromosome was diagnosed, 46,Y, dup (X)(q21.2q13.3), and mosaicism was demonstrated in his mother's X chromosome. The rearranged segment was diagnosed utilizing high resolution G-band technique and FISH studies, using chromosome X total chromosome probe and DNA XIST probe. This appears to be the first report of a patient with duplication of Xq and hypothyroidism.
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PMID:Inherited inverted duplication of X chromosome in a male: report of a patient and review of the literature. 937 22

We present two unrelated children, a male and a female, with signs of ectodermal dysplasia, mental retardation, agenesis/ dysgenesis of the corpus callosum, and primary hypothyroidism. Reports of ectodermal dysplasia with CNS malformations or hypothyroidism or both are rare. We suggest that the condition we describe is a distinct entity within the large group of ectodermal dysplasia syndromes and that it has a variable clinical spectrum. As both males and females are affected and in a few reports some parents show minimal signs, the inheritance is likely to be autosomal dominant.
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PMID:Ectodermal dysplasia, primary hypothyroidism, and agenesis of the corpus callosum: variable expression of a single syndrome? 950 98

Mental retardation is a prominent feature of many neurodevelopmental syndromes. In an attempt to identify genetic components of these illnesses, we isolated and sequenced a large number of human genomic cosmid inserts containing large trinucleotide repeats. One of these cosmids, Cos-4, maps to the X-chromosome and contains the sequence of a 7.3-kb mRNA. Initial polymorphism analysis across a region of repetitive DNA in this gene revealed a rare 12-bp exonic variation (<< 1% in non-iII males) having an increased prevalence in non-Fragile X males with mental retardation (4%, P < 0.04, n = 81). This variant was not present in the highly conserved mouse homologue that has 100% amino acid identity to the human sequence near the polymorphism. Subsequent screening of two additional independent cohorts of non-Fragile X mentally retarded patients and ethnically matched controls demonstrated an even higher prevalence of the 12-bp variant in males with mental retardation (8%, P < 0.0003, n = 125, and 14%, P < 0.10, n = 36) vs the controls. Multivariate analysis was conducted in an effort to identify other phenotypic components in affected individuals, and the findings suggested an increased incidence of histories of hypothyroidism (P < 0.001) and treatment with antidepressants (P < 0.001). We conclude that the presence of this 12-bp variant confers significant susceptibility for mental retardation.
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PMID:Association of an X-chromosome dodecamer insertional variant allele with mental retardation. 970 38

Congenital hypothyroidism is a common preventable cause of mental retardation. The overall incidence is approximately 1:4000; females are affected about twice as often as males. Approximately 85% of cases are sporadic, while 15% are hereditary. The most common sporadic etiology is thyroid dysgenesis, with ectopic glands more common than aplasia or hypoplasia. While the pathogenesis of dysgenesis is largely unknown, some cases are now discovered to be the result of mutations in the transcription factors PAX-8 and TTF-2. Loss of function mutations in the thyrotropin (TSH) receptor have been demonstrated to cause some familial forms of athyreosis. The most common hereditary etiology is the inborn errors of thyroxine (T4) synthesis. Recent mutations have been described in the genes coding for the sodium/iodide symporter, thyroid peroxidase (TPO), and thyroglobulin. Transplacental passage of a maternal thyrotropin receptor blocking antibody (TRB-Ab) causes a transient form of familial congenital hypothyroidism. The vast majority of infants are now diagnosed after detection through newborn screening programs using a primary T4-backup TSH or primary TSH test. Screening test results must be confirmed by serum thyroid function tests. Thyroid scintigraphy, using 99mTc or 123I, is the most accurate diagnostic test to detect thyroid dysgenesis or one of the inborn errors of T4 synthesis. Thyroid sonography is nearly as accurate, but it may miss some cases of ectopic glands. If maternal antibody-mediated hypothyroidism is suspected, measurement of maternal and/or neonatal TRB-Ab will confirm the diagnosis. The goals of treatment are to raise the serum T4 as rapidly as possible into the normal range, adjust the levothyroxine dose with growth to keep the serum T4 (or free T4) in the upper half of the normal range and the TSH normal, and maintain normal growth and development while avoiding overtreatment. An initial starting dose of 10-15 microg/kg per day is recommended; this dose will decrease on a weight basis over time. Serum T4 (or free T4) and TSH should be monitored every 1-2 months in the first year of life and every 2-3 months in the second and third years.
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PMID:Congenital hypothyroidism: etiologies, diagnosis, and management. 1044 22

Although mental retardation associated with congenital hypothyroidism (CH) is prevented by newborn screening and early treatment, affected children still undergo a brief period of thyroid hormone deficiency reflecting etiology of thyroid disease, illness severity, and treatment factors. Because thyroid hormone is essential for normal brain development and because some processes require thyroid hormone in the period when thyroid hormone was lacking, children with CH treated early may still have subtle neurocognitive deficits. As the period when thyroid hormone is needed differs for different brain regions, there may be different types of deficits depending on when thyroid hormone levels were insufficient. Since 1980, we have been following a large cohort of Toronto-based children with congenital hypothyroidism identified by newborn screening from infancy to adolescence. Early findings revealed a 5-10-point decline in IQ, poorer visuomotor and visuospatial abilities, delayed speech and language development, selective neuromotor deficiencies, and poorer attention and memory skills, which were correlated with different disease and treatment factors. Now a comparison between 48 subjects at adolescence and matched controls indicates that deficits persist in visuospatial, memory, and attention domains and these are correlated with severity of early hypothyroidism. Negative relationships between attention indices and thyroxine (T4) elevations at time of testing also suggest a role for thyroid hormone in the regulation of attention.
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PMID:Congenital hypothyroidism: long-term outcome. 1044 23


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