Hereditary hemochromatosis: progress and perspectives

Abstract

Hereditary hemochromatosis is an autosomal recessive disorder of iron metabolism which leads to iron overload and organ failure. Clinical symptoms develop in mid‐life and are prevalent in males. If the disease is diagnosed before the onset of cirrhosis, treatment by phlebotomy normalizes life expectancy. To demonstrate the increased iron stores, liver biopsy has been the gold standard for diagnosis. The discovery of the HFE gene and of a prevalent mutation has had a great impact on the early detection of the disorder. Molecular diagnosis is now feasible for patients using noninvasive tests. Because the molecular defect identifies only the propensity to absorb excess iron, in the presymptomatic state molecular diagnosis must be combined with other tests to demonstrate iron overload. A minority of patients with hemochromatosis have wild‐type HFE. Two distinct disorders have been recognized among these patients. Young individuals with a severe iron loading may have juvenile hemochromatosis, a disorder linked to chromosome 1q. A subset of patients with adult presentation has a type of hemochromatosis linked to chromosome 7q, characterized by inactivation of transferrin receptor 2. These new findings may have an impact on diagnosis and are of relevance for a novel view of iron metabolism.

Hemochromatosis Mistakenly Treated as Rheumatoid Arthritis

“…New, hook-like bone formations on the heads of the metacarpal bones are critical radiological signs that signal the presence of HH. [7][8][9] In our patient, the clinical and radiological characteristics of joint involvement supported our diagnosis of HH.…”

Hereditary iron overload: Update on pathophysiology, diagnosis, and treatment

“…Regarding the pathogenesis of HFE-related hemochromatosis, also called classic HH, it is difficult to 5 g), while the remainder is in iron-containing proteins (0.4 g) and bound to transferrin in plasma (5 mg) and in its storage form as ferritin or hemosiderin (0.5-1 g) [4]. To be absorbed, the dietary iron, which is mainly in the poorly soluble and absorbable ferric state, must be reduced from the ferric to the ferrous state by ferric reductase, expressed on the luminal surface of the duodenum.…”

“…Thus, in this alternative model, hepcidin emerges as a central pathogenic factor in HFE-related hemochromatosis. With respect to clinical manifestations, the classic hereditary hemochromatosis is characterized by a slow, progressive accumulation of iron in various organs and usually becomes clinically apparent during the fourth or fifth decade of life [4]. However, the clinical presentation of HH has changed significantly during the last years.…”

“…In Italy, transferrin saturation should be established before proceeding to genetic testing for the C282Y mutation, considering the low frequency of this mutation in Italy when compared with Northern European countries and the presence of other hemochromatosis types [9]. Thus, a rational approach should consist of an initial assessment of iron parameters in order to select those individuals (with transferrin saturation >45%) for subsequent genotyping [4,61]. Although screening relatives of iron-loaded homozygotes is a widely accepted strategy, recent studies have shown that the clinical expression of C282Y homozygosity is much lower than expected, confuting the cost-benefit and the cost-utility of a general population-based screening for hemochromatosis [4,48].…”

“…It is an inborn error of iron metabolism characterized by increased intestinal iron absorption, which leads to a progressive accumulation of iron in the body [2,3]. Excess iron causes tissue damage and fibrosis with irreversible damage to various organs [4][5][6]. Although HH has been known since the 19 th century, its genetic background has been clarified, at least partially, in the last few years [7][8][9].…”