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Pathogenesis of genetic haemochromatosis
Author(s) -
STREMMEL W.,
RIEDEL H. D.,
NIEDERAU C.,
STROHMEYER G.
Publication year - 1993
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1111/j.1365-2362.1993.tb02031.x
Subject(s) - transferrin , cirrhosis , organelle , pathogenesis , hemochromatosis , biology , pathophysiology , transferrin receptor , microbiology and biotechnology , chemistry , biochemistry , endocrinology , medicine , genetics , immunology
. Genetic haemochromatosis is an autosomal recessive inherited iron overload disease. The genetic defect and the underlying metabolic error are not known. Several observations indicate that the 2–4‐fold increase of iron absorption is due to a regulatory defect of a membrane iron transport system in duodenal mucosal cells. The key pathophysiologic factor may be the increase of gut‐derived non‐transferrin bound iron liganded to low‐molecular mass organic molecules. A putative membrane carrier protein for nontransferrin bound iron was identified and preliminary data suggest its enrichment in plasma membranes of human mucosal cells as well as in liver and other organs which are affected in genetic haemochromatosis. Cellular accumulation of ionic iron leads to peroxidative decomposition of organelle membrane phospholipids with the consequence of cell degeneration and cell death. Impairment of organ function and structural alterations such as cirrhosis of the liver are clinical manifestations.