Hyperferritinaemia without positive HFE gene mutation

Editor, – I read the article about testing for HFE-related haemochromatosis with interest (Aust Prescr 2011;34:73-6). Over the last 10 years I have ordered ferritin tests in over 1211 individual patients – 229 of them were found to have abnormally elevated ferritin levels. Haemochromatosis gene testing was ordered for 120 of them and there were 47 positive results. This means a significant cohort of patients with elevated ferritin do not have a positively identified mutation. My casual observation seems to give the impression that a significant number of these patients are Asian people.

Anecdotally, diabetes and lipid control in many of these patients improved when they started donating blood regularly.

My hypothesis is that:

• there are more genotypes yet to be discovered which are responsible for elevated ferritin levels in Asian people
• this (undetected and untreated) elevated ferritin may deposit in the pancreas and liver, and to some extent contributes to the high rate of diabetes and fatty livers that are so prevalent in Asian people.

Unfortunately, this is just a hunch and I do not have the detailed breakdown of these tests.

Chenault Doug Lee
General practitioner
Erindale Medical Practice, ACT

Professor Crawford, Dr Stuart and Dr St John, authors of the article, comment:

We thank Dr Lee for his interesting comments and important observations. He has raised a number of issues that are worthy of further consideration. Whilst non-HFE related iron overload is uncommon, some cases have been described in Asian patients.

Our research team has methodology to sequence many genes involved in iron metabolism, and we would be happy to assist Dr Lee (and other clinicians) to define the exact nature of the genetic defect in his Asian patients who do not carry conventional mutations in the HFE gene.

However, as Dr Lee infers, the cause of the elevated serum ferritin concentration in the majority of his Asian patients is hepatic necroinflammation, often due to non-alcoholic fatty liver disease. The growing frequency of this problem probably reflects increased exposure of his patients to a Western diet rich in carbohydrates and saturated fats. Dr Lee infers that his patients benefit from venesection, and there is some evidence to support an improvement in insulin resistance associated with such therapy. There is also recent evidence of a strong association between altered iron metabolism and lipid metabolism. However, the benefit of venesection in patients with non-alcoholic fatty liver disease, elevated serum ferritin concentration and heterozygosity for HFE mutations in relation to lipid profiles, cardiovascular mortality and liver histology is controversial and awaits definitive study.