Hereditary hemochromatosis: pathogenesis and clinical features of a common disease.
Hereditary hemochromatosis (HHC) is a common inherited disorder of iron metabolism characterized by excessive iron absorption and the toxic accumulation of iron in parenchymal cells. Homozygous inheritance of an abnormality on chromosome 6 causes this disorder by increasing the intestinal absorption of iron, which is slowly deposited in parenchymal cells of the liver, heart, pancreas, and other endocrine organs. Symptoms develop only after the marked accumulation of iron stores develop, which causes functional insufficiency of these organs. The symptoms are often variable, nonspecific, and attributed to other diseases. Early diagnosis requires a high index of suspicion and an awareness of the clinical features of HHC. Serum iron, total iron-binding capacity (TIBC), and ferritin levels are useful screening studies, but liver biopsy with quantitative chemical determination of iron concentration is essential to evaluate histopathological changes and to help distinguish hereditary hemochromatosis from secondary iron overload. Treatment with weekly phlebotomy frequently results in some clinical improvement in patients with established disease, and if initiated early, organ damage can be prevented and a normal life-span can be expected. The hereditary nature of the disease mandates familial screening of index cases.
Nichols
G M
GM
Department of Medicine, Louisiana State University, School of Medicine, Shreveport.
Bacon
B R
BR
D006432:Hemochromatosis / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D006801:Humans