Hereditary Haemochromatosis

Abstract

2021 marked the 25th anniversary of the discovery of the HFE gene, a major genetic breakthrough which revolutionised the understanding and diagnosis of hereditary haemochromatosis (HH). The original description of the condition ‘bronze diabetes’ is now rare with earlier presentations being the norm due to increased awareness and easier diagnosis. Importantly, a diagnosis of HH can be made quite readily now in primary care via HFE genotyping. Liver biopsy is reserved for fibrosis staging although non-invasive methods such as transient elastography are becoming complementary. Cirrhosis impacts on survival, and certain manifestations, such as arthritis, do not respond well to phlebotomy; the latter is a source of long-term morbidity in many patients, hence the need to diagnose the condition early. Asymptomatic HFE positive individuals may not necessarily benefit from immediate therapeutic venesection, e.g. pre-menopausal females with normal ferritin, elderly patients and compound heterozygotes. Importantly, the National Blood Service will consider treated HH individuals for maintenance phlebotomy, which provides benefit to other patients. Clinicians require a low index of suspicion for diagnosis and should implement cascade screening once a case is identified. The identification of HFE spawned a new era of molecular genetic research and a number of rarer inherited forms of iron overload have since been recognised; advanced genetic testing is now more readily available for clinicians and novel molecular therapies are in development.