ABSTRACT
La enfermedad celíaca es una enteropatía autoinmune que aparece como respuesta a la ingesta de gluten en sujetos genéticamente predispuestos. Aunque históricamente se la ha considerado una patología pediátrica e infrecuente su prevalencia está próxima al 1% de la población general, siendo todavía más elevada en pacientes con determinadas patologías endocrinológicas y déficits nutricionales. El empleo de los anticuerpos antitransglutaminasa y antiendomisio y la endoscopia digestiva con toma de biopsia serán elementos clave para su diagnóstico. La instauración de una dieta sin gluten logrará la recuperación del trofismo intestinal y evitará el riesgo de complicaciones a largo plazo a la vez que mejora la calidad de vida del paciente. El seguimiento médico y nutricional será clave para lograr una buena adherencia terapéutica (AU)
Celiac disease is an autoinmune enterophaty induced by the ingestion of gluten in genetically susceptible individuals. Although historically it was thought that it was an infrequent pediatric disease, now it is know that its prevalence is close to 1% in the general population. It is even higher between patients with some endocrine disorders and nutritional deficits. The use of antitransglutaminase and antiendomisium antibodies and the endoscopical duodenal biopsy are the cornerstones for its diagnosis. The introduction of a gluten-free diet will achieve the normalization of the intestinal mucosa. It will avoid the risk of long term complications and an it will achieve an improvement in quality of life. Medical and dietitian long term follow-up will be important to improve the compliance to the treatment (AU)
Subject(s)
Humans , Male , Female , Adult , Celiac Disease/epidemiology , Transglutaminases , Endoscopy, Digestive System , Biopsy , Celiac Disease/diet therapyABSTRACT
CONTEXT: Thyroglobulin (TG) gene mutations cause congenital hypothyroidism (CH) with goiter. A founder effect has been proposed for some frequent mutations. Mutated proteins have a defect in intracellular transport causing intracellular retention with ultrastructural changes that resemble an endoplasmic reticulum storage disease. OBJECTIVE: To reveal new aspects of thyroglobulin pathophysiology through clinical, cellular, molecular, and genetic studies in a family presenting with CH due to TG mutations from Galicia, an iodine-deficient area of Spain. DESIGN: The included clinical evaluation of family members, DNA sequencing for TG gene mutation and haplotyping analysis, ultrastructural analysis of thyroid tissue specimens from affected subjects, analysis of effects of mutations found on TG gene transcription, and in vitro studies of cellular production and secretion of mutated proteins. SETTING: Locations included primary care and university hospitals. RESULTS: Family members with CH, mental retardation, and goiter were compound heterozygous for c.886C-->T (p.R277X) and g.IVS35+1delG. For c.886C-->T, a founder effect cannot be excluded, and its transcription was hardly detectable. g.IVS35+1delG caused an in-frame deletion in exon 35 and produced a protein that, although synthesized, could not be secreted. Ultrastructural analyses showed morphological changes consistent with an endoplasmic reticulum storage disease. CONCLUSION: The shorter thyroglobulin resulting from the novel g.IVS35+1delG was retained within the endoplasmic reticulum of thyrocytes, and together with p.R227X caused severe hypothyroidism with goiter. p.R277X, the most commonly described TG mutation, is caused by a TG exon-7 highly mutation-prone region, and the possibility that some cases were introduced to South America from Galicia cannot be excluded.
Subject(s)
Congenital Hypothyroidism/genetics , Goiter/genetics , Thyroglobulin/genetics , Adult , Blotting, Western , Cells, Cultured , Genetic Testing , Haplotypes , Humans , Immunoprecipitation , Male , Microscopy, Electron , Mutation/genetics , Pedigree , SpainABSTRACT
Celiac disease is an autoimmune enterophaty induced by the ingestion of gluten in genetically susceptible individuals. Although historically it was thought that it was an infrequent pediatric disease, now it is know that its prevalence is close to 1% in the general population. It is even higher between patients with some endocrine disorders and nutritional deficits. The use of antitransglutaminase and antiendomisium antibodies and the endoscopical duodenal biopsy are the cornerstones for its diagnosis. The introduction of a gluten-free diet will achieve the normalization of the intestinal mucosa. It will avoid the risk of long term complications and an it will achieve an improvement in quality of life. Medical and dietitian long term follow-up will be important to improve the compliance to the treatment.
