The Natural History of Ferroportin Disease – First Results of the International, Multicenter EASL non-HFE Registry

Background  Ferroportin disease is caused by heterozygous mutations in SLC40A1, characterized by high serum ferritin and hepatic iron overload. Prognosis and management of patients with SLC40A1 mutations has been inferred from HFE associated hemochromatosis, despite different phenotypic presentation in patients with ferroportin disease. The aim of the present study was to define the clinical and biochemical characteristics and management of patients with SLC40A1 mutations.

Methods  The EASL non-HFE hemochromatosis registry study was set up to collect structured information on the clinical presentation, biochemistry, radiology, family history, genetics, and histology of patients with ferroportin disease. Data were compared with an age and sex matched cohort of patients diagnosed with HFE hemochromatosis.

Results  As of April 2022, 85 patients (43 women) with genetically confirmed ferroportin disease have been registered. Eighteen different mutations were reported. Patients with ferroportin disease had significantly lower serum iron, ferritin, and transferrin saturation when compared with HFE hemochromatosis patients. Hepatic iron concentration, determined by MRI, was 112.2 (±77.4) μmol/g in the ferroportin disease group as compared to 123.2 (±107.1) μmol/g in the HFE hemochromatosis group (p  = 0.618). Four patients with ferroportin disease died (mean age 81 years). Sixty-two percent of ferroportin patients (45/73) received regular phlebotomies (mean treatment duration 7.3 years, 0.98 phlebotomies per month).

Conclusion  In patients with SLC40A1 mutations, mean hepatic iron concentration was similar compared to HFE hemochromatosis. Lower serum iron and transferrin saturation are associated with better outcome in ferroportin disease, despite low rate of iron reduction therapy in patients with SLC40A1 mutations.

Publication History

Article published online:
24 May 2023