Adult hereditary fructose intolerance

Hereditary fructose intolerance(HFI) is an underrecognized,preventable life-threatening condition.It is an autosomal recessive disorder with subnormal activity of aldolase B in the liver,kidney and small bowel.Symptoms are present only after the ingestion of fructose,which leads to brisk hypoglycemia,and an individual with continued ingestion will exhibit vomiting,abdominal pain,failure to thrive,and renal and liver failure.A diagnosis of HFI was made in a 50-year-old woman on the basis of medical history,response to fructose intolerance test,demonstration of aldolase B activity reduction in duodenal biopsy,and molecular analysis of leukocyte DNA by PCR showed homozygosity for two doses of mutant gene.HFI may remain undiagnosed until adult life and may lead to disastrous complications following inadvertent fructose or sorbitol infusion.Several lethal episodes of HFI following sorbitol and fructose infusion have been reported.The diagnosis can only be suspected by taking a careful dietary history,and this can present serious complications.

Differential roles of EPS8 in carcinogenesis:Loss of protein expression in a subset of colorectal carcinoma and adenoma

AIM:To analyze the epidermal growth factor receptor pathway substrate 8(EPS8) expression status and role in colorectal carcinogenesis given that EPS8 has a conserved actin barbed-end capping function that is required for proper maturation in intestinal cells.METHODS:We studied 8 colon cancer cell lines and 58 colorectal tumors(19 adenomas and 39 carcinomas).We performed expression microarray analysis of colon cancer cell lines followed by loss of heterozygosity(LOH)analysis and immunohistochemistry for EPS8 expression in colon tumors.Subsequently,we performed mutation analysis by direct sequencing and methylation analysis by bisulfite sequencing and methylation-specific polymerase chain reaction assays.RESULTS:Expression microarray analysis of colon cancer cell lines showed overexpression of EPS8 transcript in all lines but RKO.Genome wide loss of heterozygosity(LOH) analysis of colon tumors,showed considerable LOH at the EPS8 gene locus.Immunohistochemically,EPS8 was constitutively expressed in normal colonic mucosa with a dot-like supranuclear localization with accentuation at the luminal surface supporting its proposed role in epithelial maturation.Nineteen colon tumors(4 adenoma,15 carcinoma) out of 51(37%) showed strikingly tumor specific EPS8 protein loss.Of the remaining tumors,5/51(2 adenoma,and 3 carcinoma,10%) showed marked overexpression,while 27/51 tumors(53%) showed retained expression.Mutation analysis revealed a missense mutation(c.794C>T,p.R265C) in exon 8 in RKO.The EPS8 promoter was also methylated in RKO,but there was no significant methylation in other cell lines or carcinoma specimens.CONCLUSION:The loss of EPS8 expression in colorectal adenomas and carcinomas suggests that down regulation of this gene contributes to the development of a subset of colorectal cancers,a finding which could have applications in diagnosis and treatment.