Iron Overload - Diagnosis

Diagnosis

There are several methods available for diagnosing and monitoring iron loading including:

• Serum ferritin
• Liver biopsy
• HFE
• MRI

Serum ferritin is a low-cost, readily available, and minimally invasive method for assessing body iron stores. However, the major problem with using it as an indicator of iron overload is that it can be elevated in a range of other medical conditions unrelated to iron levels including infection, inflammation, fever, liver disease, renal disease, and cancer. Also, total iron binding capacity may be low, but can also be normal.

The standard of practice in diagnosis of haemochromatosis was recently reviewed by Pietrangelo. Positive HFE analysis confirms the clinical diagnosis of haemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals with a family history of haemochromatosis. The alleles evaluated by HFE gene analysis are evident in ~80% of patients with haemochromatosis; a negative report for HFE gene does not rule out haemochromatosis. In a patient with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated. In this case, diagnosis of haemochromatosis is based on biochemical analysis and histologic examination of a liver biopsy. Assessment of the hepatic iron index (HII) is considered the "gold standard" for diagnosis of haemochromatosis.

MRI is emerging as an alternative to liver biopsy for measuring liver iron loading. For measuring liver iron concentrations, R2-MRI (also known as FerriScan) has been extensively validated. More than 11,000 FerriScans have now been conducted in over 120 medical centres across 25 countries. FerriScan is now specifically recommended as a method to measure liver iron concentrations in clinical practice guidelines for thalassaemias, sickle cell disease myelodysplastic syndrome (MDS) and hereditary haemochromatosis.

Family members of those diagnosed with primary haemochromatosis may be advised to be screened genetically to determine if they are a carrier or if they could develop the disease. This can allow preventative measures to be taken.