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Magnetic resonance imaging to identify classic and nonclassic forms of ferroportin disease
Antonello Pietrangelo1, Elena Corradini, Francesca Ferrara
1Center for Hemochromatosis, Department of Internal Medicine, University Hospital of Modena and Reggio Emilia, Policlinico, Via del Pozzo 71 41100 Modena, Italy. pietrangelo.antonello@unimo.it
Abstract:
The ferroportin-related disorder is an increasingly recognized cause of hereditary iron overload. Based on the in vitro behavior of different ferroportin mutant subsets, it was suggested that different forms of the disorder might exist in humans. We used MRI to address this question in vivo in 22 patients from four different pedigrees carrying different ferroportin mutations: A77D, N144H, G80S and Val 162del. We found that, based on the iron status of spleen and bone macrophages, two different forms of the disease can be identified: a classic, common form, characterized by hepatocyte, splenic macrophage and bone marrow macrophage iron retention in patients carrying the A77D, G80S and Val 162del ferroportin variants; a rarer non-classic form, associated with liver iron overload but normal spleen and bone marrow iron content in patients with the N144H mutation. The two forms are likely caused by lack- or gain-of-protein function, respectively. Interestingly, in treated patients with the classic form, the spleen and the spine show appreciable iron accumulation even when serum ferritin is normal and liver iron content low. In conclusion, MRI is a useful non-invasive diagnostic tool to categorize and diagnose the disorder, monitor the status of iron depletion and gain insights on its natural history and management.
Insights
Two forms of ferroportin-related disorder, a hereditary iron overload condition, have been identified using MRI. This non-invasive tool helps diagnose and manage the disease by assessing iron levels in spleen and bone macrophages.
Area of Science:
- Biochemistry
- Genetics
- Radiology
Background:
- Ferroportin-related disorder is an emerging cause of hereditary iron overload.
- In vitro studies suggested potential for distinct human disease forms based on ferroportin mutations.
Purpose of the Study:
- To investigate in vivo if different ferroportin mutations lead to distinct clinical forms of hereditary iron overload.
- To utilize MRI for differentiating these potential disease forms.
Main Methods:
- Magnetic Resonance Imaging (MRI) was employed to assess iron status in 22 patients from four pedigrees with distinct ferroportin mutations (A77D, N144H, G80S, Val 162del).
- Iron content in hepatocytes, splenic macrophages, and bone marrow macrophages was evaluated.
Main Results:
- Two distinct forms were identified: a classic form (A77D, G80S, Val 162del mutations) with iron retention in liver, spleen, and bone marrow macrophages; and a non-classic form (N144H mutation) with liver iron overload but normal spleen and bone marrow iron.
- These forms are hypothesized to result from loss-of-function and gain-of-function mutations, respectively.
- In treated classic form patients, spleen and spine iron accumulation persisted even with normal serum ferritin and low liver iron.
Conclusions:
- MRI is a valuable non-invasive tool for diagnosing and categorizing ferroportin-related disorders.
- MRI aids in monitoring iron depletion status and provides insights into disease natural history and management.
- Distinct clinical presentations correlate with specific ferroportin mutations, suggesting different pathomechanisms.
