by Dr. Adele Visser
Introduction
Hereditary haemochromatosis (HC) is a condition characterized by uncontrolled gastrointestinal iron absorption which if not managed, may lead to iron deposition and serious, life-threatening complications.
It is the most common genetic disorders amongst Caucasian affecting 1:200 to 1:400 individuals.
Pathophysiology
Various mutations in the iron metabolism have been implicated, also with variance in clinical manifestations (table 1).
Table 1. (Types of HC and the associated mutations)
Clinical approach to suspected HC
Iron overload should be considered in patients presenting with endocrinopathies, arthralgia, skin pigmentation changes, hepatomegaly, osteopaenia and new onset cardiac symptoms. The most common reported symptoms in general practice is fatigue and arthopathy. It should be considered that men typically present in their 30’s whereas women typically only present post-menopausally.
The first-line investigation should be a serum ferritin. In males, levels greater than 300 µg/L and females greater than 200 µg/L are considered excessive requiring further investigation. It should be noted that ferritin is an acute phase reactant and may therefore increase in response to a host of conditions other than HC. The transferrin saturation may also be useful, where cases in excess of 45% are considered abnormal.
Further evaluation should prompt a thorough consideration of other secondary causes, including excessive alcohol use, polymetabolic syndrome, inflammation, acute or chronic hepatitis, ferritin-cataract syndrome, Gaucher’s disease and macrophase-activation syndrome.
If a diagnosis of HC is still considered, genetic testing can be undertaken, starting with HFE testing. The HFE assay tests for various mutations in this gene family, including the C282Y, H63D and S65C mutations.
If this does not confirm the diagnosis, consider testing for other mutations including TfR2, Hepcidin and ferroportin. Genetic mutations can confirm the diagnosis. However, the absence of a positive mutation in the setting of clinical haemochromatosis should not discourage the diagnosis, as other described and yet-to-be described variants exist.
Long-term considerations
• If a patient has a confirmed diagnosis of HC, familial screening should be considered
• Patients with serum ferritin levels in excess of 1000 µg/L should undergo further investigation to
evaluate visceral iron deposition through either imaging studies or liver biopsy
• In patients with confirmed HC, close monitoring should be performed for all known complications
of this condition including but not limited to:
• Endocrine evaluation including sex hormones
• Bone density screening
• Restrict iron intake and avoid iron and vitamin C supplementation
• Consider therapeutic venesection a manner of excess iron removal
• Iron chelation can also be considered in patients where venesection is not an option
References
Girelli D., Busti F et al. 2002. Hemochromatosis classification: update and recommendations by the BIOIRON society. Blood 139(20): 3018-3029