RT Book, Section A1 Smith, Benjamin A1 Grace, Norman D. A2 Greenberger, Norton J. A2 Blumberg, Richard S. A2 Burakoff, Robert SR Print(0) ID 55960919 T1 Chapter 41. Hereditary Hemochromatosis T2 CURRENT Diagnosis & Treatment: Gastroenterology, Hepatology, & Endoscopy, 2e YR 2012 FD 2012 PB The McGraw-Hill Companies PP New York, NY SN 978-0-07-176848-1 LK accessmedicine.mhmedical.com/content.aspx?aid=55960919 RD 2024/03/28 AB Hemochromatosis classically refers to HFE-mediated genetic iron overload, but several alternatively mediated genetic iron overload syndromes have been described.C282Y is the major mutation and H63D the minor mutation of the HFE gene; individuals with two copies of C282Y or one copy of both mutations (compound heterozygote) are at risk for iron overload.Excess iron deposition in tissues leads to end-organ damage; advanced hemochromatosis typically involves the liver first and may also involve the pancreas, heart, pituitary gland and other organs.Most patients are identified by laboratory screening or family history and are asymptomatic at diagnosis.Symptomatic patients usually present with nonspecific complaints of fatigue, arthralgias, and abdominal pain.Screening studies include serum iron/total iron-binding capacity (abnormal if >45% in women, >50% in men) and serum ferritin (abnormal if >200 mcg/dL in women, >300 mcg/dL in men); if either test is positive, genetic testing should be pursued.Liver biopsy to assess iron concentration and hepatic iron index is indicated if serum ferritin is >1000 mcg/dL, liver tests are abnormal, or hepatomegaly is noted on physical examination.