RESUMEN
Dietary fat is an important source of nutrition. Here we identify eight mutations in SARA2 that are associated with three severe disorders of fat malabsorption. The Sar1 family of proteins initiates the intracellular transport of proteins in COPII (coat protein)-coated vesicles. Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell.
Asunto(s)
Grasas de la Dieta/farmacocinética , GTP Fosfohidrolasas/genética , Síndromes de Malabsorción/enzimología , Síndromes de Malabsorción/genética , Mutación , Vesículas Cubiertas por Proteínas de Revestimiento/enzimología , Quilomicrones/metabolismo , Femenino , GTP Fosfohidrolasas/química , Enfermedad del Almacenamiento de Glucógeno Tipo IV/enzimología , Enfermedad del Almacenamiento de Glucógeno Tipo IV/genética , Humanos , Absorción Intestinal , Síndromes de Malabsorción/metabolismo , Masculino , Modelos Moleculares , Linaje , Conformación Proteica , Degeneraciones Espinocerebelosas/enzimología , Degeneraciones Espinocerebelosas/genéticaRESUMEN
OBJECTIVES: The protein calprotectin is mainly derived from neutrophils. Increased fecal excretion of calprotectin has been reported in inflammatory bowel disease. The recommended cut-off level in adults (<50 microg/g feces) seems to be applicable in children aged 4 to 17 years. The aim of this study was to evaluate the use of fecal calprotectin to detect colorectal inflammation in children with gastrointestinal symptoms. METHODS: We obtained stool samples on thirty-six children with gastrointestinal symptoms and suspected inflammation of the colon before they underwent colonoscopy. The samples were examined with an improved fecal calprotectin enzyme-linked immunosorbent assay method (Calprest, Eurospital). The results were correlated with the histopathologic findings in the colon. RESULTS: In children with colorectal inflammation (n = 22) the median fecal calprotectin concentration was 349 microg/g (range, 15.4-1860 microg/g). The most common diagnosis in this group was inflammatory bowel disease. Median fecal calprotectin was 16.5 microg/g (range, 5.0-65 microg/g) in children with no inflammation (n = 14). When <50 microg/g was used as upper reference limit the fecal calprotectin test had a sensitivity of 95%, specificity 93%, positive predictive value 95% and negative predictive value 93% to detect colorectal inflammation. CONCLUSIONS: The improved fecal calprotectin enzyme-linked immunosorbent assay is a simple test with potential use in children. Increased fecal calprotectin strongly predicted the presence of colorectal inflammation in children with gastrointestinal symptoms. Fecal calprotectin can be used to select patients who should undergo diagnostic colonoscopy for investigation of colorectal inflammation, including inflammatory bowel disease.