Health Concerns

Hemochromatosis

Diagnosis and Conventional Treatment

Given the potential involvement of elevated tissue iron in the progression of several seemingly unrelated diseases, surveillance of total body iron content may present an important measure of disease prevention. Historically, excessive iron has been diagnosed only after sufficient damage has occurred to reveal characteristic symptoms (hyperpigmentation, liver enlargement, and joint problems); however, there are several tests that can monitor iron status before signs & symptoms of frank iron overload occur. Annual blood testing for iron load can allow early detection of sub-clinical elevations that can be addressed by diet, lifestyle changes, and/or conventional therapies (Heli 2011; Fleming 2012; Muñoz 2011).

Diagnosis

Serum ferritin and transferrin saturation are blood tests that can detect iron overload, even before symptoms appear (Heli 2011; Fleming 2012; Muñoz 2011).

Serum ferritin. This test measures the iron storage protein ferritin in the blood serum. While typically an intracellular storage protein, blood levels of ferritin increase proportionally to body stores (1 ng/ml of serum ferritin represents approximately 8 mg of stored iron) (Muñoz 2011). Infection, inflammation or liver disease can elevate serum ferritin levels, complicating measurements in individuals with these conditions; a high-sensitivity C-reactive protein (hs-CRP) test can be used to rule out inflammation (Heli 2011).

Transferrin Saturation. Transferrin saturation (TSAT) measures the ratio of serum iron and total iron-binding capacity of transferrin multiplied by 100 (Muñoz 2011). Elevated TSAT is seen in several genetic causes of iron overload (Fleming 2012).

Other important tests include:

Serum Iron. Serum iron measures the total iron in blood serum (Muñoz 2011).

Total Iron Binding Capacity. Total iron binding capacity (TIBC) measures total binding capacity of transferrin (the iron transport protein) in the serum (an indirect measurement of transferrin) (Muñoz 2011).

HFE Test. A HFE test is a genetic test for the presence of either of the two main mutations (C282Y and H63D) of the HFE gene. These mutations are the most common causes of hereditary hemochromatosis. An individual with Type I hemochromatosis generally carries two copies of the C282Y gene, or one copy of each mutant gene (Santos 2012). Positive HFE analysis confirms the clinical diagnosis of hemochromatosis in asymptomatic individuals with blood tests showing increased iron stores; it is also predictive of risk in individuals with a family history of hemochromatosis (Pietrangelo 2010).

Liver biopsy. Liver biopsy can be used as a direct measure of non-heme iron and for the diagnosis of non-HFE hemochromatosis. Liver iron concentrations of greater than 15 mg/g dry weight increase the risk of iron-associated cardiovascular disease and early death. The threshold for liver injury and fibrosis is about 22 mg/g (Muñoz 2011).

The development of MRI (magnetic resonance imaging) of the liver and heart now offers a non-invasive method for assessing iron stores in these organs. R2-MRI (also known as FerriScan) is now specifically recommended as a method to measure liver iron concentrations in clinical practice guidelines. It is also used for monitoring the efficacy of iron chelation therapy (Taher 2008; Fischer 2009; Muñoz 2011).