Hemochromatosis is a disease that involves a progressive elevation of total body iron stores, eventually leading to abnormal iron deposition into multiple organs. There are two main classifications of hemochromatosis:
Primary hemochromatosis is an autosomal recessive genetic disorder in which the mutations of certain genes involved in iron metabolism lead to increased intestinal iron absorption. It is most commonly caused by mutations in the HFE gene, with an estimated 2-5% of the Caucasian population being heterozygous carriers.
Secondary hemochromatosis occurs in the context of excess iron accumulation that is brought about by another cause. It is the less common than hereditary hemochromatosis and can be due to a variety of different disorders, including but not limited to: chronic hemolytic anemia, frequent transfusions, dialysis, and liver disease among others.
Commonly, hereditary causes of hemochromatosis due to HFE gene mutations tend to present between ages 40 and 60. Patients who present younger, are less common, but it is typically due to a mutation in the hemojuvelin gene, as opposed to the HFE gene. The overload of iron ends up depositing in various organs, leading to cardiovascular, skeletal, pancreatic, hepatic and CNS manifestations. Clinically, the most common findings in patients with hemochromatosis are liver function abnormalities, weakness and lethargy, bronze skin due to hyperpigmentation, arthralgia, diabetes. Less commonly, CNS abnormalities such as hypopituitarism, and movement disorders may be seen.
On imaging, the accumulated iron causes magnetic susceptibility artifact, leading to characteristic changes. The most commonly affected regions of iron deposition include the choroid plexus, anterior pituitary, circumventricular organs, and the basal ganglia. On T2 imaging and GRE/SWI, hypointense lesions are typically seen in the areas of iron deposition. However, on T1 imaging, hypo and hyperintense lesions have been reported, so the clinical circumstance should be considered while interpreting. Other neurological findings may be present on imaging due to either the causes of hemochromatosis (if non-hereditary) or due to complications of hemochromatosis, like hepatic encephalopathy. Furthermore, it should be noted that neuroradiological findings may be seen in patients with hemochromatosis without having neurologic sequelae.
References:
1. Stankiewicz J, Panter SS, Neema M, Arora A, Batt C, Bakshi R. Iron in Chronic Brain Disorders: Imaging and Neurotherapeutic Implications. Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics. 2007;4(3):371-386. doi:10.1016/j.nurt.2007.05.006.
2. https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-hereditary-hemochromatosis