Diagnosis and treatment of hereditary hemochromatosis: an update

Abstract

Hereditary hemochromatosis is an inherited iron overload disorder caused by inappropriately low hepcidin secretion leading to increased duodenal absorption of dietary iron, most commonly in C282Y homozygous individuals. This can result in elevated serum ferritin, iron deposition in various organs and ultimately end-organ damage, although there is incomplete biochemical and clinical penetrance and variable phenotypic expression of the HFE mutation in hereditary hemochromatosis. An elevated SF >1000 mg/l [corrected] is associated with an increased risk of cirrhosis and mortality in C282Y homozygotes.Conversely, a SF <1000 µg/l is associated with a very low likelihood of cirrhosis, making liver biopsy unnecessary among C282Y homozygotes in the absence of concomitant risk factors for liver disease. Phlebotomy remains the mainstay of treatment and new treatments being studied include erythrocytapheresis and 'mini-hepcidins'. Iron overload is being recognized to play a carcinogenic role in hepatocellular carcinoma and other cancers, possibly supporting iron depletion in these patients.

Recent advances in hemochromatosis: a 2015 update

“…Types I-III are linked to altered or reduced expression of hepcidin [11,25,27], whereas type IV results from reduced iron export [1,28]. Mutations in HFE, HJV, HAMP, TFR2 and SLC40A1 have been linked to the various types of hemochromatosis [11,25,29], each displaying different onsets, severities and prevalences [2,4,9,25,27,[29][30][31][32][33] (Table 1).…”

“…The C282Y substitution resulting from a missense mutation in HFE is the most common cause of hereditary hemochromatosis in Caucasian populations [25,30], with up to 90 % of hemochromatosis cases being associated with homozygosity for the mutation [9,25,30,34]. However, there is significant variance in C282Y incidence with ethnic diversity [1,29,35,36].…”

“…However, there is significant variance in C282Y incidence with ethnic diversity [1,29,35,36]. The highest allelic prevalence is in northern European populations (6 %), within which those of Celtic origin show an increased prevalence at 10-12.5 [9,37]. Looking at non-European populations, a study by Adams et al [38] found that whilst 0.44-0.68 % of Caucasians were homozygous for C282Y [36], the prevalence was only 0.11, 0.027, 0.014, 0.012 and 0.000039 % in Native American, Hispanic, Black, Pacific Islander and Asian populations respectively.…”

“…The current understanding of hemochromatosis focuses on the hepatic regulatory protein hepcidin and factors controlling its expression. At least four distinct subtypes of hemochromatosis have been recognised and described, each with distinct genetic and molecular profiles [9].…”

“…Phlebotomy intervals are adjusted on an individual basis. Although there is some debate on the recommended maintenance range for SF, the current accepted standard remains at 50-100 lg/l [9,12].…”