UMLS:C0917816 - FACTA Search

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Query: UMLS:C0917816 (mental retardation)
15,867 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

Resistance to thyroid hormone (RTH) is a syndrome of reduced sensitivity to thyroid hormone, most commonly caused by mutations in the thyroid hormone receptor (TR) beta gene. Mutations are mostly located in the ligand-binding domain of the TRbeta, decreasing T(3) binding to the mutant TRbeta molecule, which in turn interferes with the function of the wild-type (WT) TR. A total of 122 different TRbeta gene mutations have been identified so far, with 46 occurring in more than one family. We now report a family with two novel TRbeta mutations occurring in the same nucleotide. The proposita had two children from each of her two marriages. One daughter and one son from each marriage had severe RTH with free T(4) and T(3) levels 3- to 4-fold the mean normal values and unsuppressed TSH, mental retardation, and deafness. The proposita had a missense mutation (GTG to GGG) in codon 458 of the TRbeta gene, resulting in the replacement of the normal valine with glycine (V458G). Although this mutation was transmitted to her affected son, the mutated codon in her affected daughter was GAG, encoding glutamic acid (V458E). Haplotype analysis showed that this de novo mutation occurred on the already mutant allele of the proposita. Cotransfection of each of these mutant TRbetas with the wild-type TRbeta showed a potent dominant negative effect. Large amounts of T(3) were required to dissociate homodimers of the mutant TRbeta bound to DNA. In addition, and in contrast to other mutant TRbetas with severe T(3)-binding defects, homodimer release failed to recruit the steroid receptor coactivator. No defects in heterodimerization with retinoid X receptor-alpha or association with a nuclear receptor corepressor, were identified. These in vitro data are in agreement with the in vivo phenotype of severe RTH. Unique and previously unreported in human inherited diseases is the occurrence of a de novo mutation at an already mutant nucleotide. Because the occurrence by chance is extremely unlikely, it is postulated that the presence of three guanines in the sequence created by the mutant nucleotide of the proposita results in a mutagenic site prone to de novo mutation.
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PMID:A de novo mutation in an already mutant nucleotide of the thyroid hormone receptor beta gene perpetuates resistance to thyroid hormone. 1559 85

In Indonesia, newborn screening is not yet a policy, and the incidence of preventable causes of mental retardation detected by newborn screening is not known. Congenital hypothyroidism (CH) is not infrequent. Without a screening program, unrecognized CH patients were neglected for years. Since May 1999, the International Atomic Energy Agency (IAEA) has assisted in starting a CH Newborn Screening Project to estimate the local incidence of CH and to evaluate the problems associated with the screening. In June 2000, a pilot study was conducted using primary TSH measurement, supplemented by T4 in infants with elevated TSH. The target was to screen 12,000 newborn infants, using cord blood serum taken at birth, or a heel prick between 2 to 6 days of age. Between June 2000 and February 2001, 3,534 neonates born in 4 hospitals were screened using cord blood serum taken at birth (recall rate 3.3%). From March 2001 onwards, the heel prick method was used and participating hospitals increased from 4 to 7. Using this approach, until August 2001, 3,309 samples were analysed and the recall rate was much lower (0.64%). The number of unsatisfactory samples was relatively high due to an unstable process of blood collection. Parental refusal and low acceptance of screening among policy makers resulted from lack of awareness of the dangers of CH, and the screening program was not considered a health priority. Recall of patients after screening was a major barrier, with problems in tracking patients arising from urbanization and a high rate of relocation. To advance the CH screening program nationwide, infrastructure must be improved along with the recall system, and education as well as information campaigns for parents and medical professionals must be intensified. The Department of Health must be persuaded to give a national mandate.
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PMID:Newborn screening in Indonesia. 1590 1

Primary congenital hypothyroidism is a common preventable cause of mental retardation. Neonatal thyroid screening is highly successful in early diagnosis and the improvement of developmental prognosis in the hypothyroid neonate. However, rarely cases could be missed, so doctors must be aware of the earl symptoms and signs of hypothyroidism. Therefore, the purpose of this study was to emphasize the presenting clinical features of primary congenital hypothyroidism at the age of diagnosis. The study population included 17 children with primary congenital hypothyroidism who attended the Department of Pediatrics, University Clinical Center Tuzla between 1986 and 1999. The diagnosis of all patients was confirmed by serum thyroid function tests (T4 and TSH). Of the 17 patients 10 (58.8%) were diagnosed in the first three months of life and 3 of them (17.6%) between fourth and sixth month of life. Four children (23.5%) were diagnosed after the age of six months. In the first three months of life hypothermia, constipation, jaundice, poor feeding, hoarse cry, macroglossia and hypoactivity were the moste common symptoms. Among the 17 patients with primary congenital hypothyroidism 5 of them (29.4 %) were diagnosed to have disgenetic thyroid tissue and 12 (70.6%) as having dyshormonogenesis. TSH and T4 levels were higher in patients in whom thyroid tissue was dysgenetic as comapared with those with dyshormonogenesis but the difference was not statistically significant (p > 0.05). Now it is expected that neonatal screening program in Bosnia and Herzegovina Federation will contribute to the detection of primary congenital hypothyroidism in early days of life. However, until an effective screening test is not yet routine in whole country, paediatricians should consider the diagnosis of hypothyroidism whenever it is clinically suggested.
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PMID:Clinical presentation of primary congenital hypothyroidism: experience before mass screening. 1635 94

Congenital hypothyroidism (CH) is the commonest treatable cause of mental retardation. The prevelance is 1/3000 - 1/4000 live births worldwide. The importance of CH is that, the longer the diagnosis of CH is delayed, the higher the risk of mental retardation and neurologic sequale; such as poor motor coordination, ataxia, spastic diplegia, muscular hypotonia, strabismus, learning disability and diminished attention span. The most common cause of permenant CH is thyroid dysgenesis (85-90%) in which the transcription factors TTF1,TTF2 and PAX8 would appear to be obvious candidate genes in the aetiology. Especially cardiac defects and some other birth defects are described in patients with CH. Inborn errors of thyroid hormonogenesis are responsible for 10-15% of CH cases and usually have autosomal recessive inheritance, consistent with a single gene mutation. Transient CH is very common in prematures with an estimate of 10% of CH babies identified on newborn screening, or 1 in 40,000 neonates. CH neonates are usually symptom-free and the most encountered symptoms are prolonged jaundice, large fontanelles and umbilical hernia. In general, the extent of clinical findings depends on the cause, severity and duration of hypothyroidism. An elevated TSH>20 microm Iu/L and a decreased concentration of T4 confirms the diagnosis of CH. Infants with permanant abnormalities of thyroid function mostly have a serum TSH concentration > 50 microm Iu/L. Ultrasonography, thyroid scintigraphy, bone x ray of the knee and serum thyroglobulin concentration are the other essentials after diagnosis to clarify the status of the thyroid and the severity of hypothyroidism. The higher doses of 10- 15 microm g/kg/day and the commencement of treatment before 2 weeks gave rise to better long term outcome of CH patients. In the follow up of the patients noncompliance is the most important problem and serum freeT4 or T4 and TSH should be obtained at each visit to adjust the doses of L-thyroxine. Still a small number of patients with severe hypothyroidism in utero or reflected by clinical signs and symptoms extremely low T4 levels and delayed bone age may have intellectual deficits despite normal intelligence.
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PMID:Congenital hypothyroidism clinical aspects and late consequences. 1644 57

Down Syndrome (DS) or trisomy 21 (T21) is the most frequent and the best known malformation syndrome associated with mental deficiency that appears in human,. Average incidence of this syndrome is about 1:700 newborns. Numerous researchers noted thyroid disorders in people with Down Syndrome but, clinical symptoms of thyroid dysfunction are difficult to separate from DS phenotype. The aim of this study was to examine the thyroid function in the patients with DS. Our results confirmed higher frequency of thyroid dysfunction in DS patients. Higher values of TSH were found in 60,34% of the examined DS patients, which is significantly higher value comparing with the control group (p<0,01). Compensated hypothyroidism was established in 27,92% of the examined DS patients, and most of those (63,23%) were younger than 6 years. The conclusions emphasize the necessity of implementation of thyroid function screening program in persons with DS, and the need for adequate treatment of its dysfunction. Thus, the symptoms of the disease would be alleviated and better physical and mental fitness ensured.
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PMID:Down Syndrome and thyroid gland. 1699 46

Congenital hypothyroidism is the principle cause of preventable mental retardation, with a prevalence of 1 in 3,500 neonates. The disorder may be permanent or transitory. Permanent congenital hypothyroidism is caused principally by thyroid dysgenesis. In industrialized countries, mass screening allows the disorder to be diagnosed at birth. The severity is variable but is generally more pronounced in females. The majority of studies point to a genetic origin for the disease and no consistent evidence has been found to suggest a major role for environmental factors. The genetic factors have already been identified and involve several elements (mutations in the TTF-1, TTF-2, PAX8 and TSH receptor genes). The etiological diagnosis is based on scintigraphy, ultrasound and the level of circulating thyroglobulin. At present, treatment is administered at an adapted dose during the first two weeks of life and should allow the child to reach its full intellectual potential. However, minor anomalies have been reported in some treated children, suggesting that this treatment cannot compensate for a certain degree of foetal hypothyroidism.
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PMID:[Congenital hypothyroidism]. 1707 33

Most neonates born with congenital hypothyroidism (CH) have normal appearance and no detectable physical signs. Hypothyroidism in the newborn period is almost always overlooked and delayed diagnosis leads to the most severe outcome of CH, mental retardation, emphasizing the importance of neonatal screening. Blood spot T4 or TSH or both can be used in neonatal screening for CH. The latter, which is more sensitive, is not cost effective, so the first two are used in different programs in the world. TSH screening was shown to be more specific in the diagnosis of CH; T4 screening is more sensitive in detecting newborns especially with rare hypothalamic-pituitary hypothyroidism, but less specific with a high frequency of false positives mainly in low birth weight and premature infants. The time at which the sample is taken may vary between centers, with the majority taking blood from a heel prick after 24 hours of age to minimize the false positive high TSH due to the physiological neonatal TSH surge that elevates TSH levels and causes dynamic T4 and T3 changes in the first 1 or 2 days after birth. Early discharge of mothers postpartum has increased the ratio of false positive TSH elevations. Although transient hypothyroidism may occur frequently, all suspected infants should be treated as having CH for the first 3 years of life, taking into account the risks of mental retardation. A reevaluation after 3 years is needed in such patients. The goal of initial therapy in CH is to minimize neonatal central nervous system exposure to hypothyroidism by normalizing thyroid function, as reflected by T4 and TSH levels, as rapidly as possible. Iodine deficiency is the most important cause of CH worldwide. Iodine is essential for thyroid hormone synthesis and is present in soil, water and air. Prevention of iodine deficiency can be by iodized salt, iodized oil, iodized bread or iodine tablets.
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PMID:Newborn screening for congenital hypothyroidism. 1722 56

Congenital Hypothyroidism (CH) is one of the most common preventable causes of mental retardation with a worldwide incidence of 1:4000 live births. Ideally universal screening at 3-4 days of age should be done for detecting CH. Abnormal values on screening (T4 < 6.5 ug/dL, TSH > 20 micro/L) should be confirmed by a venous sample (using age appropriate cutoffs) before initiating treatment. Term as well as preterm infants with low T4 and elevated TSH should be started on L-thyroxine at a dose of 10-15 microg/ kg/ day as soon as the diagnosis is made. Regular monitoring should be done to ensure that T4 is in the upper half of normal range. The outcome of CH depends on the time of initiation of therapy and the dose of L-thyroxine used with the best outcome in infants started on treatment before 2 weeks of age with a dose > 9.5 microg/ kg/ day.
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PMID:Congenital hypothyroidism. 1853 92

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