Clinical ResearchClinical and pathologic findings in hemochromatosis type 3 due to a novel mutation in transferrin receptor 2 gene☆,☆☆
Section snippets
The family
The proband, a 32-year-old man, was referred to the Department of Clinical and Experimental Medicine at the University of Verona for reevaluation of an iron overload disease previously detected elsewhere. Clinical history showed no alcohol intake, blood transfusions, or excess oral iron intake. At the age of 16 years, the patient underwent biochemical tests for scleral jaundice. Increased serum levels of bilirubin (2.8 mg/dL, predominantly unconjugated) and iron (230 μg/dL) were detected.
Clinical findings
The first liver biopsy specimen of the proband was recovered and reviewed. Histopathologic evaluation showed normal lobular architecture, no significant fibrosis, and hepatocellular hemosiderin deposits of grade III according to Scheuer et al.28 (Figure 2A and B).
Discussion
The present description of a family carrying a new mutation of the TFR2 gene further supports the role of this gene as causative for HH type 3. Affected members from this family showed an early-onset disease because iron overload was detected before the age of 30 years in all of them, including the woman (II:4). This feature and the clinical findings of patient II:2 were apparently consistent with the diagnosis of juvenile hemochromatosis, the most severe form of HH, characterized by rapidly
Acknowledgements
The authors thank the members of the family (especially the proband), Dr. Alberto Piperno from the University of Milano-Bicocca for measuring hepatic iron concentration, and Dr. Daniela Bertuzzi, on behalf of the blood banks of San Bonifacio and Verona, for their cooperation.
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Address requests for reprints to: Domenico Girelli, M.D., Ph.D., Department of Clinical and Experimental Medicine, University of Verona, Policlinico G.B. Rossi, 37134 Verona, Italy. e-mail: [email protected]; fax: (39) 45-580111.
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Supported by Telethon grants E.749 (to D.G.) and GP 0255Y01 (to C.C.) and by the European Community (contract QLRT-1999-02237).