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Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Even though early treatment of congenital hypothyroidism (CH) with newborn screening prevents the mental retardation previously seen in cretinism, affected children still exhibit subtle persisting neurocognitive deficits. One of their commonest problems is poor attention, which reflects both early disease severity and later (high) circulating thyroid hormone levels. While attention is currently regarded as multicomponential in nature, with different processing components supported by different brain regions, the specific components of attention affected by CH have not been identified. In light of animal evidence showing that neonatal thyroid hormone deficiencies impede the neurodevelopment of structures important for selective aspects of attention, we proposed a multicomponential approach to study attention in children with CH. This was accomplished via retrospective analysis of existing data on adolescents with CH whose attention was previously evaluated using multiple tests. Results showed significantly poorer overall attention in CH than controls with differences occurring mainly on focus and inhibit indices. However, performance on various indices was associated with different disease parameters. Poor encode and focus were correlated with more severe hypothyroidism and a longer period of thyroid hormone insufficiency and poor select and shift with higher thyroid hormone levels at testing. These results signify that thyroid hormone is important for the development and later regulation of brain structures supporting distinct aspects of attention.
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PMID:Attention problems in adolescents with congenital hypothyroidism: a multicomponential analysis. 1157 95

Resistance to thyroid hormone (RTH) is a syndrome in which patients have elevated thyroid hormone (TH) levels and decreased sensitivity to its action. We describe a child with extreme RTH and a severe phenotype. A 22-month-old female presented to the NIH with goiter, growth retardation, short stature, and deafness. Additionally, the patient had hypotonia, mental retardation, visual impairment, and a history of seizures. Brain magnetic resonance imaging showed evidence of demyelination and bilateral ventricular enlargement. The patient had markedly elevated free T3 and free T4 levels of more than 2000 pg/dl (normal, 230-420 pg/dl) and more than 64 pmol/liter (normal, 10.3-20.6 pmol/liter), respectively, and TSH of 6.88 mU/liter (normal, 0.6-6.3 mU/liter). These are the highest TH levels reported for a heterozygous RTH patient. A T3 stimulation test confirmed the diagnosis of RTH in the pituitary and peripheral tissues. Molecular analyses of the patient's genomic DNA by PCR identified a single base deletion in exon 10 of her TRbeta gene that resulted in a frameshift and early stop codon. This, in turn, encoded a truncated receptor that lacked the last 20 amino acids. Cotransfection studies showed that the mutant TR was transcriptionally inactive even in the presence of 10(-6) M T3 and had strong dominant negative activity over the wild-type receptor. It is likely that the severely defective TRbeta mutant contributed to the extreme RTH phenotype and resistance in our patient.
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PMID:Extreme thyroid hormone resistance in a patient with a novel truncated TR mutant. 1170 67

Newborn screening for congenital hypothyroidism (CH), is one of the major achievements of medicine because early diagnosis and treatment has resulted in normal development in the vast majority of cases. However, all studies on outcome report up to 10% of patients with residual problems regarding mental development and neurological symptoms despite early diagnosis. Factors clearly associated with a less favourable outcome are late onset and an inadequate dosage of thyroid hormone substitution, a poor social-economic environment and compliance problems, while the impact of severity of CH at diagnosis on outcome is not completely settled, although most studies demonstrate a correlation between severity of hypothyroidism and poorer outcome. More recently in a few cases the molecular basis of CH has been clarified. It has become evident that, in some patients with persistent mental retardation and neurological symptoms, defects in transcription factors which are expressed in the thyroid gland as well as in the central nervous system (CNS) during embryonic development cause both defective thyroid and CNS development. The clarification of further molecular defects which affect the thyroid gland and brain development will help us to understand the poor outcome of patients with CH in the era of newborn screening and these diagnostic advances will ensure adequate counselling and care for these patients.
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PMID:Long-term consequences of congenital hypothyroidism in the era of screening programmes. 1206 98

Table salt can now be fortified with iodine and iron without interaction and without loss of potency. According to Levente Diosady, professor of Food Engineering at the University of Toronto, the amounts of the two micronutrients available to the human body have been significantly reduced when the two interacted. In the new technology, the iodine is covered with a dextrin (a water soluble starch) capsule that serves as a physical barrier to the iron. Micronutrient Initiative (an international secretariat based at IDRC that works to eliminate health problems resulting from iron, iodine, and vitamin A deficiencies) and IDRC supported the development of the technology. The efficiency of absorption of the two micronutrients in the new double fortified salt in the human body is being tested at the Hospital for Sick Children in Toronto. Later testing will be conducted by University of Ghana scientists in IDRC-funded trials that will focus on women and their families in areas of Ghana where these deficiencies are endemic. Iodine is part of thyroid hormone, which contributes to brain development in the fetus and regulates human metabolism; iodine deficiency is the most frequent cause of preventable mental retardation. Related disorders include lethargy, physical disabilities, goiter, stillbirth, and neonatal death. Iron deficiency, the most common nutritional problem in the world (particularly among women, infants, and children), is associated with anemia, fatigue, learning problems, pregnancy complications, premature births, and maternal mortality. The two deficiencies together affect more than one-third of the world's population. Approximately 1.6 billion people, in more than 100 countries, live in areas where iodine is not available in sufficient amounts; those most at risk include about one-third of China's population. It is also a severe problem in the Himalayas, the Andes, India, and West Africa.
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PMID:Micronutrient deficiencies. Reports from the field -- Africa. 1229 Mar 27

Fetal alcohol exposure is the most common nonhereditary cause of mental retardation in the western world. Rats prenatally treated with ethanol liquid diet exhibit extensive defects in the brain that accurately model those observed in humans. To analyze the ethanol effects on gene expression during brain development, we performed mRNA differential display and two-dimensional electrophoresis on gestational day (G) 13 and G 16 brain from rats treated with ethanol liquid diet. Using mRNA differential display followed by a variety of quantitative analyses, three genes were confirmed to be ethanol-responsive. Among them was Neuroendocrine-Specific Protein-A (NSP-A), which is known to be affected by thyroid hormone in the cortex at this developmental time. However, two additional genes known to be thyroid hormone-responsive were unaffected by ethanol, indicating that interference with thyroid hormone action may not be a predominant pathway by which alcohol induces damage in the fetal brain. The observation that interferon-inducible protein-10 (IP-10) is up-regulated in ethanol-treated fetal brain may indicate the presence of a disease process recruiting CD8+ T-cells capable of interfering with myelination. The result of two-dimensional (2D) electrophoresis and Western analyses demonstrated that few changes in the abundance of individual proteins or the phosphorylation of proteins at threonine and tyrosine were induced by prenatal ethanol exposure. A critical analysis of the approaches used in the present study may be important for future studies in this field.
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PMID:Differential display identifies neuroendocrine-specific protein-A (NSP-A) and interferon-inducible protein 10 (IP-10) as ethanol-responsive genes in the fetal rat brain. 1235 40

Because thyroid hormone is essential for normal brain development, children born with congenital hypothyroidism who lack thyroid hormone during a circumscribed period of early development are at risk of brain damage and mental retardation. Since the advent of newborn screening programs in the 1980s, the diagnosis and treatment of this condition are now provided in the first 2-3 weeks of birth in most regions. While this is usually sufficient to prevent mental retardation, the children so identified attain mildly reduced IQs from expectation, and may still experience subtle and specific neurocognitive deficits. Their particular deficits are related to the brief period of thyroid hormone insufficiency they undergo, especially factors reflecting the severity of hypothyroidism at the time of diagnosis, the duration of hypothyroidism in infancy, and thyroid hormones at time of testing. In this article, we review the specific kinds of deficits demonstrated by children with congenital hypothyroidism who were diagnosed by screening and treated early, as well as the factors associated with their disease and its management that contribute to these deficits. The disease-related factors that will be reviewed will include the etiology of hypothyroidism and severity of disease at the time of diagnosis, while the treatment-related factors will include age at onset of therapy, starting and subsequent dose levels, compliance, and treatment-adequacy issues. Also examined will be the effects of hormone levels at the time of testing. In addition, the role of moderating variables such as social, genetic, and environmental influences, as well as the child's gender, will be discussed. Furthermore, several new issues including the quality of subsequent management, ultimate outcome, and pregnancy will be additionally reviewed. In conclusion, while outcome in congenital hypothyroidism is substantially improved by screening, affected children do still experience mild neuropsychologic deficits. To reduce the impact of persisting deficits, further research is needed to determine the optimal starting dose for the different etiologies, guidelines for subsequent management, and alternative therapies. Moreover, now that the original samples are reaching adulthood and, in females, childbearing age, further research is also needed regarding treatment during pregnancy in women with congenital hypothyroidism, as is research to determine how this population ultimately fares in adulthood.
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PMID:Congenital hypothyroidism: a review of current diagnostic and treatment practices in relation to neuropsychologic outcome. 1260 79

The main changes in thyroid function associated with the pregnant state are increased thyroid hormone requirements. These increased requirements can only be met by a proportional increase in hormone production, that directly depends upon the availability of dietary iodine. When the iodine intake is adequate, normal "physiological" adaptation takes place. When the intake is restricted, physiological adaptation is progressively replaced by pathological alterations, in parallel with the degree of iodine deprivation, leading to excessive glandular stimulation, hypothyroxinemia, and goiter formation. Thus, pregnancy acts typically as a revelator of underlying iodine restriction and gestation results in an iodine deficient status, even in conditions with only a moderately restricted iodine intake, characteristic of many European regions. Iodine deficiency during pregnancy has important repercussions for both mother and fetus, namely thyroid underfunction and goitrogenesis. Furthermore, iodine deficiency may be associated with alterations of the psychoneuro-intellectual outcome in the progeny. The risk of an abnormal progeny's development is further enhanced because mother and offspring are exposed to iodine deficiency, both during gestation and the postnatal period. Because iodine deficiency is still prevalent in many European regions and remains a subject of great concern, investigators have proposed, since several years, that iodine prophylaxis be introduced systematically during pregnancy, in order to provide mothers with an adequate iodine supply. In areas with a severe iodine deficiency, correcting the iodine lack has proved highly beneficial to prevent mental deficiency disorders. The many actions undertaken to eradicate severe iodine deficiency have allowed to prevent the occurrence of mental retardation in millions young infants throughout the world. In most public health programmes dealing with the correction of iodine deficiency disorders, iodized salt has been used as the preferred strategy in order to convey the iodine supplements to the household. Iodized salt, however, is not the ideal vector in the specific instance of pregnancy (or breastfeeding) or in young infants, because of the necessity to limit salt intake. Hence, particular attention is required in our countries to ensure that pregnant women have an adequate iodine intake, by administering multi-vitamin tablets containing iodide supplements (+125 micro g/d). Finally, it is with some concern that the results of a recent nutritional survey in the USA have disclosed that iodine deficiency, long thought to have been eradicated since many years, may actually show a resurgence, particularly in women in the child-bearing period. This issue needs to be considered seriously by the medical community and public health authorities.
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PMID:Feto-maternal repercussions of iodine deficiency during pregnancy. An update. 1270 32

Congenital hypothyroidism (CH) is a neonatal disorder that is caused by a prolonged loss of thyroid hormone, which is essential for early brain development. While CH was once the leading cause of mental retardation, newborn screening for CH now allows for early identification and treatment. As a result, affected children now show normal physical and psychological development. Nevertheless, because they still undergo a brief but circumscribed period of thyroid hormone insufficiency, they are at risk for subtle selective impairments. This paper examines several of the persisting deficits observed in children with CH that was identified early in life by newborn screening as well as the relevant disease- and treatment-related factors contributing to such deficits. Highlighted will be (a) a weakness in visuospatial processing, which is associated with prenatal thyroid hormone insufficiency, (b) selective memory deficits associated with postnatal thyroid hormone insufficiencies, (c) a weakness in sensorimotor abilities also reflecting postnatal thyroid hormone insufficiencies, and (d) attention deficits, which are due to abnormal thyroid hormone levels at time of testing. Because these four disabilities implicate different neural substrates, the findings described presently will provide insights as to the specific time windows when different brain structures in the human critically need thyroid hormone.
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PMID:Congenital hypothyroidism: an analysis of persisting deficits and associated factors. 1275 31

In Japan, mass screening tests on newborns for Cretinism have been performed since 1984, Cretinism is a very rare condition. We report the clinical course and complications of longitudinal thyroid hormone replacement therapy (liothyronine sodium: T3) of two women with Cretinism and ectopic thyroid gland for the past 33 years until 2001. They were born in April 1951 (Case 1) and in January 1952 (Case 2). On admission in June 1968, they were 17 and 16 years old. They had short stature, mental retardation, macroglossia, saddle nose, retardation of bone maturation, edematous face, coexistence of permanent teeth and deciduous teeth, abdominal distention, hypotonia, anemia, hypophosphatemia and hypercholesterolemia. After admission, Case 2 had an appendectomy for appendicitis. She was found to have a right ovarian cyst, but was not operated upon. Later, the right ovarian cyst disappeared during thyroid hormone replacement therapy. The complication in this case was NIDDM. Over secretion of thyroid hormone in for example, hyperthyroidism sometimes induces NIDDM. On their admission, a levothyroxine sodium (T4: Thyradin S) was unavailable in Japan, so we had no choice but to treat them with liothyronine sodium for thyroid hormone replacement therapy. We suspect that liothyronine sodium replacement therapy probably induced NIDDM. They experienced improved bone maturation, anemia, hypophsphatemia and hypercholesterolemia, but their intellectual and mental disabilities were not improved.
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PMID:The longitudinal course of two cases with cretinism diagnosed after adolescence. 1280 80

The human opposite paired-containing (HOPA) gene is believed to be a co-activator of the thyroid hormone receptor and involved in thyroid hormone signal transduction. The gene consists of 45 exons and includes a dodecamer duplication in exon 43, which has been reported to be associated with mental retardation, autism, psychiatric disorders and hypothyroidism. We were interested to know if the 12-bp duplication variant of the HOPA gene is a risk factor for mental retardation and schizophrenia in the Chinese population. We investigated the prevalence of the 12-bp variant in a sample of Chinese mental retardation and schizophrenic patients from Taiwan by PCR-based genotyping. None of the mentally retarded and schizophrenic patients were found to have this dodecamer duplication variant. Our results indicate that the HOPA polymorphism might be very rare in our population and is unlikely to be a major risk factor for mental retardation and schizophrenia in the Chinese population.
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PMID:No association of a dodecamer duplication in the human opposite paired (HOPA) gene with mental retardation and schizophrenia in Chinese patients from Taiwan. 1286 Mar 70


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