RESUMO
BACKGROUND: Recently, the first patients with resistance to thyroid hormone alpha (RTHα) due to inactivating mutations in the thyroid hormone receptor alpha (TRα) were identified. These patients are characterized by growth retardation, variable motor and cognitive defects, macrocephaly, and abnormal thyroid function tests. The objective was to characterize a young girl (18 months old) with a mutation in both TRα1 and TRα2, and to study the effects of early levothyroxine (LT4) treatment. METHODS: The patient was assessed clinically and biochemically before and during 12 months of LT4 treatment. In addition, the consequences of the mutation for TRα1/2 receptor function were studied in vitro. RESULTS: At 18 months of age, the patient presented with axial hypotonia, delayed motor development, severe growth retardation, and abnormally elevated triiodothyronine (T3)/thyroxine (T4) ratios. RTHα was suspected, and concomitantly a c.632A>G/p.D211G missense mutation was identified, affecting both the TRα1 and TRα2 proteins. This mutation was also found in the girl's father. LT4 treatment was started, resulting in a marked improvement of her hypotonia, motor skills, and growth. Functionally, the missense mutation led to decreased transcriptional activity of TRα1, which could be overcome by higher T3 levels in vitro. The mutant TRα1 showed a moderate dominant negative activity on wild type (WT) TRα1. In contrast, WT TRα2 and mutant TRα2 had negligible transcriptional activity and showed no dominant-negative effect over TRα1. CONCLUSIONS: This report describes the phenotype of a young RTHα patient with a mild TRα mutation before and during early LT4 treatment. Treatment had beneficial effects on her muscle tone, motor development, and growth.
Assuntos
Mutação de Sentido Incorreto , Receptores alfa dos Hormônios Tireóideos/genética , Síndrome da Resistência aos Hormônios Tireóideos/genética , Linhagem Celular , Desenvolvimento Infantil , Análise Mutacional de DNA , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Linhagem , Fenótipo , Testes de Função Tireóidea , Receptores alfa dos Hormônios Tireóideos/agonistas , Receptores alfa dos Hormônios Tireóideos/metabolismo , Síndrome da Resistência aos Hormônios Tireóideos/sangue , Síndrome da Resistência aos Hormônios Tireóideos/diagnóstico , Síndrome da Resistência aos Hormônios Tireóideos/tratamento farmacológico , Tiroxina/uso terapêutico , Transfecção , Resultado do TratamentoRESUMO
Dental decay and dental treatment are suggested to be related to body growth in children. The aim of this study was first to assess the relation between dental caries and body proportions cross-sectionally in a Suriname caries child population and secondly to investigate whether dental treatment had a significant influence on body growth of these children in a randomised controlled trial using different treatment strategies. Three hundred eighty 6-year-old children with untreated dental decay participated in the study. Caries prevalence and presence of dentogenic infections were recorded. All children were randomly assigned to four different treatment groups ranging from full dental treatment to no invasive treatment at all. Body growth was evaluated by children's height, weight and body mass index. Participants were evaluated after 6 months and 1, 2 and 3 years. Cross-sectionally, negative correlations were observed between anthropometric measures and the number of untreated carious surfaces and caries experience of the children. Next, no significant differences in growth pattern between the treatment groups were observed. Based on these results, it is suggested that caries activity is a negative predictor for body growth in children and dental intervention does not show significant improvement within 3 years.
