Hemochromatosis

A man in his mid-30s was found to have a markedly elevated ferritin level (>2500 μg/L) and a serum transferrin saturation of 95%. A liver biopsy was performed. A Perls iron stain demonstrated severe iron overload, with iron deposited in the hepatocytes. The patient then underwent genetic testing, which identified homozygous C282Y mutations in the HFE gene. Which of the following is true about hereditary hemochromatosis?a.The most common cause is mutation of the HFE geneb.Women are more likely than men to be affected by clinical diseasec.Clinical disease typically is manifested in children and teenagersd.The iron deposition does not lead to liver damage, only heart damage Answer: a. The most common cause of hereditary hemochromatosis is mutation involving HFE. HFE mutations can lead to excess iron absorption from the small bowel, leading to iron deposition in various organs, including the liver. The most common disease-causing mutations in the HFE gene are C282Y and H63D. C282Y has been linked to northern European genetic ancestry.1Hanson E.H. Imperatore G. Burke W. HFE gene and hereditary hemochromatosis: a HuGE review. Human Genome Epidemiology.Am J Epidemiol. 2001; 154: 193-206Crossref PubMed Scopus (383) Google Scholar Most patients with hemochromatosis present as middle-aged or older adults, and men are more likely than women to develop clinical disease.2Allen K.J. Gurrin L.C. Constantine C.C. et al.Iron-overload-related disease in HFE hereditary hemochromatosis.N Engl J Med. 2008; 358: 221-230Crossref PubMed Scopus (568) Google Scholar The HFE mutations impair the function of hepcidin, a regulator of iron in the body.3Pietrangelo A. Hepcidin in human iron disorders: therapeutic implications.J Hepatol. 2011; 54: 173-181Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar Hemochromatosis can lead to liver cirrhosis and to hepatocellular carcinoma.4Niederau C. Fischer R. Purschel A. et al.Long-term survival in patients with hereditary hemochromatosis.Gastroenterology. 1996; 110: 1107-1119Abstract Full Text Full Text PDF PubMed Scopus (810) Google Scholar Other organs can also have iron deposition and damage, including the heart and pancreatic islet cells (which can lead to heart failure and diabetes, respectively).