Long-term consequences of congenital hypothyroidism in the era of screening programmes

Grüters, Annette; Jenner, A. A. J.; Krude, Heiko

doi:10.1053/beem.2002.0202

Cited by 62 publications

(28 citation statements)

References 50 publications

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“…82,83 Also, MR owing to congenital hypothyroidism is now largely preventable through screening and hormone replacement. 84 Other examples of efficient therapeutic approaches are dietary restrictions and supplements for inborn errors of metabolism such as phenylketonuria. 85,86 Another example suggesting that cognitive deficits could, to a certain extent, be partially reversible is provided through the autosomal form of inborn errors of creatine biosynthesis that corresponds to guanidinoacetate methyltransferase (GAMT) deficiency.…”

Section: Resultsmentioning

confidence: 99%

Genetics and pathophysiology of mental retardation

et al. 2006

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Mental retardation (MR) is defined as an overall intelligence quotient lower than 70, associated with functional deficit in adaptive behavior, such as daily-living skills, social skills and communication. Affecting 1-3% of the population and resulting from extraordinary heterogeneous environmental, chromosomal and monogenic causes, MR represents one of the most difficult challenges faced today by clinician and geneticists. Detailed analysis of the Online Mendelian Inheritance in Man database and literature searches revealed more than a thousand entries for MR, and more than 290 genes involved in clinical phenotypes or syndromes, metabolic or neurological disorders characterized by MR. We estimate that many more MR genes remain to be identified. The purpose of this review is to provide an overview on the remarkable progress achieved over the last decade in delineating genetic causes of MR, and to highlight the emerging biological and cellular processes and pathways underlying pathogeneses of human cognitive disorders.

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Section: Resultsmentioning

confidence: 99%

Genetics and pathophysiology of mental retardation

et al. 2006

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“…Isolated MR with no other consistent defining features MR due to congenital hypothyroidism is now largely is known as nonspecific or nonsyndromal MR. To date, preventable through screening and hormone replaceall but one of these (Molinari et al 2002) are X-linked, ment (Gruters et al 2002). Aside from this, the only but other autosomal genes may have eluded identificamolecular-based therapeutic approaches are dietary retion because of the considerably greater difficulty of strictions and supplements for inborn errors of metabomapping disorders to autosomal loci.…”

Section: Ental Retardation (Mr) Is a Common Formmentioning

confidence: 99%

“…We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR. Isolated MR with no other consistent defining features MR due to congenital hypothyroidism is now largely is known as nonspecific or nonsyndromal MR. To date, preventable through screening and hormone replaceall but one of these (Molinari et al 2002) are X-linked, ment (Gruters et al 2002). Aside from this, the only but other autosomal genes may have eluded identificamolecular-based therapeutic approaches are dietary retion because of the considerably greater difficulty of strictions and supplements for inborn errors of metabomapping disorders to autosomal loci.…”

mentioning

confidence: 99%

Molecular and Comparative Genetics of Mental Retardation

2004

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Affecting 1-3% of the population, mental retardation (MR) poses significant challenges for clinicians and scientists. Understanding the biology of MR is complicated by the extraordinary heterogeneity of genetic MR disorders. Detailed analyses of Ͼ1000 Online Mendelian Inheritance in Man (OMIM) database entries and literature searches through September 2003 revealed 282 molecularly identified MR genes. We estimate that hundreds more MR genes remain to be identified. A novel test, in which we distributed unmapped MR disorders proportionately across the autosomes, failed to eliminate the well-known X-chromosome overrepresentation of MR genes and candidate genes. This evidence argues against ascertainment bias as the main cause of the skewed distribution. On the basis of a synthesis of clinical and laboratory data, we developed a biological functions classification scheme for MR genes. Metabolic pathways, signaling pathways, and transcription are the most common functions, but numerous other aspects of neuronal and glial biology are controlled by MR genes as well. Using protein sequence and domainorganization comparisons, we found a striking conservation of MR genes and genetic pathways across the ‫007ف‬ million years that separate Homo sapiens and Drosophila melanogaster. Eighty-seven percent have one or more fruit fly homologs and 76% have at least one candidate functional ortholog. We propose that D. melanogaster can be used in a systematic manner to study MR and possibly to develop bioassays for therapeutic drug discovery. We selected 42 Drosophila orthologs as most likely to reveal molecular and cellular mechanisms of nervous system development or plasticity relevant to MR. Isolated MR with no other consistent defining features MR due to congenital hypothyroidism is now largely is known as nonspecific or nonsyndromal MR. To date, preventable through screening and hormone replaceall but one of these (Molinari et al. 2002) are X-linked, ment (Gruters et al. 2002). Aside from this, the only but other autosomal genes may have eluded identificamolecular-based therapeutic approaches are dietary retion because of the considerably greater difficulty of strictions and supplements for inborn errors of metabomapping disorders to autosomal loci.

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“…A preparação hormonal tireoidiana de escolha para o tratamento é a T4 (levotiroxina), já que a maior parte do hormônio tireoidiano nas células do SNC deriva da conversão local de T4 em T3 (6,12,20,21,43). Somente comprimidos de levotiroxina deverão ser utilizados, uma vez que não existe aprovação de soluções líquidas desse hormônio (11).…”

Section: Discussionunclassified

“…Dentro das características que um bom método de triagem neonatal deve ter, encontram-se: ampla cobertura populacional, e aqui o ideal seria chegar a 100% dos recém-nascidos vivos (11), baixa porcentagem de reconvo-cações ou falso-positivos (11,12,14,23,42,43), reduzido número de perdas ou falso-negativos (6,33), possibilidade de combinação com outros métodos de rastreamento (24,25), disponibilidade de meios técnicos adequados para confirmação diagnóstica e etiológica (6,22,24,25), possibilidade de iniciar o tratamento precocemente e assegurar seguimento dos afetados (6,24,25,(36)(37)(38)43).…”

Section: Discussionunclassified

Situação atual da triagem neonatal para hipotireoidismo congênito: críticas e perspectivas

Nascimento

2011

Arq Bras Endocrinol Metab

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SUMÁRIOO hipotireoidismo congênito (HC) é uma das causas mais frequentes de deficiência mental passível de prevenção. Esforços devem ser utilizados na sua detecção e no tratamento precoces. O atraso no diagnóstico e no tratamento resultará em sequela neurocognitiva. A triagem neonatal mudou a evolução natural dessa enfermidade. O nível de corte do TSH utilizado é 10 mUI/l. No Brasil, a triagem neonatal é realizada há três décadas. Atualmente todos os estados brasileiros e o Distrito Federal a realizam. Analisando os últimos dados do Programa Nacional de Triagem Neonatal (PNTN), observamos que existe uma diferença enorme entre os Serviços de Referência nos vários estados. A cobertura do PNTN é de 81,61% dos recém-nascidos. Apenas 56,94% colheram a amostra até sete dias de vida. Os tempos médios da coleta até a chegada da amostra ao laboratório, da realização da dosagem do TSH, da liberação do resultado e reconvocação das crianças suspeitas estão fora do preconizado, culminando numa idade média de início de tratamento muito acima da ideal. Isso resulta na impossibilidade de cumprimento do principal objetivo da triagem, que é o início precoce do tratamento para a prevenção de sequelas. Estudos recentes têm sugerido mudança do nível de corte do TSH para 6 mUI/l para reduzir os falso-negativos. Medidas devem ser adotadas para que os índices ideais do PNTN sejam atingidos. Arq Bras Endocrinol Metab. 2011;55(8):528-33 Descritores Triagem neonatal; hipotireoidismo congênito SUMMARY Congenital hypothyroidism (CH) is one of the most common treatable causes of mental retardation. Efforts should be done in its early detection and treatment. Delays in diagnosis and treatment will result in impaired neurocognitive outcomes. Neonatal screening changed the natural history of this disease. The cutoff value for TSH is 10 mUI/L. In Brazil, neonatal screening has been done for three decades. Currently, it is performed in all Brazilian States and the Brazilian Federal District. Looking at recent data on the National Program for Neonatal Screening (NPNS) we can see a huge difference in the results among Brazilian States. NPNS involved 81.61% of the newborns. Only in 56.94% of the cases, samples were collected from newborns up to 7 days of life. Mean time of collection to arrival of the specimen in the lab, TSH determination, release of results and summoning the patient are far longer than the ideal times, causing a delay in early treatment to prevent neurological sequelae. Recent studies have suggested that changing TSH cutoff values to 6 mUI/L may reduce false negative results. Strategies should be adopted to achieve the goals established by the NPNS. Arq Bras Endocrinol Metab. 2011;55(8):528-33

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Long-term consequences of congenital hypothyroidism in the era of screening programmes

Cited by 62 publications

References 50 publications

Genetics and pathophysiology of mental retardation

Genetics and pathophysiology of mental retardation

Molecular and Comparative Genetics of Mental Retardation

Situação atual da triagem neonatal para hipotireoidismo congênito: críticas e perspectivas

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