Hemochromatosis is an iron overload disorder characterized by a progressive increase in total body iron stores and deposition of iron in some non-reticuloendothelial system (RES) body organs which results in some instances in organ dysfunction.

This article focus on the general principles of hemochromatosis, as well as effects of iron accumulation in the liver, the most frequently affected organ. Clinical and imaging changes in other organ systems are discussed separately:


Hemochromatosis may be primary which is a genetic disorder or secondary which can result from a variety of diseases.

Primary hemochromatosis

Primary hemochromatosis is primarily (90%) due to an abnormal HFE gene, the protein product of which regulates iron absorption from the gastrointestinal tract. The two most common HFE gene mutations are C282Y and H63D. Homozygosity for the C282Y mutation and heterozygosity for C282Y/H63D mutations (also called compound heterozygosity) result in iron overload .

Approximately 2-5% of the population are heterozygous carriers (Caucasian population), resulting in a 0.2-0.5% prevalence of homozygous individuals . This makes hemochromatosis one of the most common genetic disorders in Caucasians of Northern European ancestry.

Although the genetic defect is distributed equally among men and women, the iron loss as a result of menstruation is protective, resulting in a clinical male predilection (M:F ~ 2:1).

In men, the diagnosis usually becomes evident in middle age (30-40 years of age) whereas, in women, clinical manifestation is delayed until the post-menopausal period.

Secondary hemochromatosis

Secondary hemochromatosis is rare and is usually seen in association with diseases that chiefly cause hemosiderosis. The distribution of iron in both RES and non-RES tissues can thus assist in the imaging differentiation between primary and secondary disease .

  • frequent transfusion
    • mainly depositional siderosis in the reticuloendothelial system (RES)
    • if > 40 units transfused: then may cause hemochromatosis (non-RES iron deposition)
  • high erythrogenic requirements (hemolytic anemia, myelodysplasia)
    • mainly depositional siderosis in RES from transfusion
    • increased duodenal iron absorption may lead to hemochromatosis (non-RES iron deposition)
  • bantau siderosis: rare cause in Africa due to iron-laden locally-brewed beer

Clinical presentation

As hemochromatosis may affect a number of organ systems, patients not surprisingly may present with a variety of signs and symptoms. These are most pronounced in primary hemochromatosis and include :


The fundamental pathology that underlies hemochromatosis is the accumulation of iron and an increase in total body iron stores (as high as 50-60g) and abnormal non-reticuloendothelial deposition, which in turn leads to organ dysfunction.

Hemochromatosis is distinct from, and should not be confused with, hemosiderosis which refers to the reticuloendothelial system (RES) iron deposition and does not cause organ damage.

Eventual organ dysfunction is the final step in a cascading sequence of events :

  • increased gastrointestinal absorption of iron
  • increased cellular uptake of iron into non-RES
  • liver is the primary organ of deposition
  • pancreatic, cardiac, skeletal, and CNS deposition can occur once hepatic deposition is extensive
  • iron gets deposited in periportal hepatocytes (ferritin and hemosiderin)
  • perilobular fibrosis ensues with fibrous septa
  • can progress to cirrhosis with broad fibrous septa surrounding large areas of relatively normal liver parenchyma

Radiographic features

General visceral features of hemochromatosis are increased organ density (CT) and reduced organ signal intensity (MRI). Secondary imaging features include hepatomegaly, cirrhosis and signs of heart failure.

The pattern of iron deposition is important. Predominant involvement of the liver, without deposition in spleen or bone marrow, is consistent with non-RES iron deposition and is characteristic of primary hemochromatosis. Iron deposition in the spleen and bone marrow, but to a lesser degree in the liver is consistent with RES deposition and is most likely due to hemosiderosis, which may or may not be associated with secondary hemochromatosis.


CT, although readily available, is not very sensitive for the diagnosis of hemochromatosis . In positive cases, marked homogeneous increase in liver density (75-130 HU) is demonstrated, making the portal vessels and hepatic veins appear of low attenuation relative to the liver on non-contrast CT.

Dual-energy CT can be used to quantitate iron deposition.


See the sub-article on MRI liver iron quantification.

MRI is not only the most sensitive imaging modality for the diagnosis of hemochromatosis but is also able to estimate iron concentration within the liver, thus forestalling the need for repeated biopsies .


Visceral iron results in susceptibility artefact which leads to T2* signal loss. The result is a low signal that is seen on all sequences, but particularly gradient echo and T2. It is useful to compare organ signal to that of skeletal muscle, with lower organ signal than muscle indicating the presence of iron.

Gradient in-phase and out-of-phase sequences are particularly useful, demonstrating changes that are the opposite of those seen in hepatic steatosis. In hemochromatosis, the liver on in-phase sequence (which is usually obtained second, and thus more susceptible to T2* effects) demonstrates low signal, whereas the out-of-phase sequence demonstrates higher signal .

In primary hemochromatosis, spleen and bone marrow signal is typically normal and low pancreatic signal is usually only seen if there is cirrhosis.


Quantitative MR techniques for measuring iron deposition have been developed, consisting of multiple gradient-echo sequences with progressively increasing TEs. The degree to which signal drops can then be plotted and an estimate of iron concentration generated. In cases with very high concentration, the method is unreliable as too little signal is returned from the liver .

Treatment and prognosis

Treatment in primary disease involves frequent phlebotomy which improves symptoms such as hepatomegaly, skin pigmentation, lethargy, and abdominal pain. However, arthritis is not affected by therapy. This also improves mild abnormalities of glucose metabolism. However, if type I diabetes mellitus has developed, insulin replacement will still be required. Some improvement in hepatic fibrosis and cardiac dysfunction can also be expected.

Secondary hemochromatosis and hemosiderosis may require iron chelation therapy, depending on the underlying cause.

Poor prognostic factors include the development of:

Differential diagnosis

General imaging differential considerations for hepatic appearances include: