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Ferritinophagy: Assessing the Selective Degradation of Iron by Autophagy in Human Fibroblasts
Published on: February 23, 2024
Hyperferritinemia and iron overload in type 1 Gaucher disease
Philip Stein1, Hannah Yu, Dhanpat Jain
1Department of Pediatrics, Yale School of Medicine, 333 Cedar Street, New Haven, CT 06520, USA.
American Journal of Hematology
|June 25, 2010
Summary
Hyperferritinemia is common in Gaucher disease, linked to disease severity and reversed by enzyme replacement therapy (ERT). It is not associated with HFE mutations.
Area of Science:
- Hematology
- Gastroenterology
- Genetics
Background:
- Hyperferritinemia is observed in Gaucher disease, but its clinical significance, association with systemic iron overload, and link to HFE mutations are unclear.
- Gaucher disease is a lysosomal storage disorder characterized by glucocerebroside accumulation, affecting various organs.
Purpose of the Study:
- To investigate the clinical spectrum of hyperferritinemia in Type 1 Gaucher disease.
- To determine the association of hyperferritinemia with systemic iron overload and HFE mutations.
- To correlate ferritin levels with disease severity and response to enzyme replacement therapy (ERT).
Main Methods:
- Serum ferritin and transferrin saturation levels were measured in 114 Type 1 Gaucher disease patients.
- HFE genotyping (H63D and C282Y mutations) was performed.
- Correlations were analyzed with hepatosplenomegaly, Gaucher disease severity, and ERT response. Liver biopsies were conducted in a subset of patients with suspected iron overload.
Main Results:
- A mean 3.7-fold elevation of serum ferritin above the upper limit of normal (ULN) was observed.
- Prior splenectomy was associated with significantly higher ferritin levels (6.53 x ULN) compared to patients with intact spleens (2.69 x ULN).
- Ferritin levels correlated with liver volume and were negatively correlated with hemoglobin, but not with other Gaucher disease activity indicators. ERT significantly reduced ferritin levels (P = 0.001). HFE genotyping showed no correlation with ferritin levels. Three patients had confirmed iron overload on liver biopsy.
Conclusions:
- Hyperferritinemia is highly prevalent in Type 1 Gaucher disease and is associated with indicators of disease severity.
- Enzyme replacement therapy effectively ameliorates hyperferritinemia.
- The observed hyperferritinemia is not linked to HFE mutations, and systemic iron overload occurs in a subset of patients.
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