Diagnosis of Hepatic Iron Overload A Family Study Illustrating Pitfalls in Diagnosing Hemochromatosis

作者：Sehranz Melanie; Talasz Heribert; Graziadei Ivo; Winder Thomas; Sergi Consolato; Bogner Klaus; Vogel Wolfgang; Zoller Heinz^*

来源：Diagnostic Molecular Pathology, 2009, 18(1): 53-60.

• iron
• hemochromatosis
• liver disease
• transplantation

Recent identification of genetic variants in iron storage disease has changed the classification system and diagnostic algorithms for hemochromatosis. Clinical diagnosis of the disease requires phenotypic evidence of iron overload because the commonly disease-associated HFE genotypes have ail incomplete penetrance. Furthermore, similar to 20% of patients with a clinical diagnosis of hemochromatosis have no disease-associated genotype, which underlines the importance of clear phenotypic criteria of hemochromatosis. A diagnosis of hemochromatosis cannot be made even in patients with liver cirrhosis simply on the basis of genetic testing that indicates that iron overload is the cause of the disease and not its consequence. Proper diagnosis requires integration of clinical presentation, family history, and the results of biochemical and histopathologic tests. Here we propose a rational diagnostic algorithm for hepatic iron overload syndromes and illustrate potential pitfalls by presenting a family study in a pedigree with rare FIFE variants (H63D and E168Q), in cis on the same chromosome. Although the clinical suspicion of hemochromatosis was confirmed by histology, chemical analysis of liver tissue revealed a normal hepatic iron concentration, which is compatible with the genetic finding of I normal and I doubly mutated allele. In conclusion, clinical suspicion of hemochromatosis and elevated serum iron parameters should prompt HFE genotyping for C282Y and H63D. Should they be uninformative, further genetic tests should be recommended only if iron overload in liver tissue has been confirmed chemically.

• 出版日期2009-3