Molecular diagnosis of hemochromatosis.

Introduction: The discovery of hemochromatosis genes and the availability of molecular-genetic tests considerably modified the knowledge of the disease relative to physiopathology, penetrance, and expression, and had major impact in the diagnostic settings.

Areas covered: Hemochromatosis is a heterogenous disorder at both genetic and phenotypic level. The review discusses criteria to define patients' iron phenotype and to use molecular tests to diagnose HFE-related and non-HFE hemochromatosis. The material examined includes articles published in the journals covered by PubMed US National Library of Medicine. The author has been working in the field of iron overload diseases for several years and has contributed 18 of the papers cited in the references.

Expert opinion: Hemochromatosis genotyping is inseparable from phenotype characterization. A full clinical assessment is needed and DNA test performed when data suggest a clear indication of suspicion of being at risk for HH. HFE testing for p.Cys282Tyr mutation and p.His63Asp variant is the first molecular diagnostic step. Genotyping for rare mutations can be offered to patients with negative first-level HFE testing who have iron overload with no other explanation and should be performed in referral centers for iron overload disorders that can provide genetic advice and in-house genotyping services.