A diagnosis of HH is based on laboratory evidence of iron overload, identification of genetic mutations associated with HH, and presence of clinical signs and symptoms consistent with HH.13 Elevated hemoglobin and hematocrit are not typically associated with HH. Iron overload is identified by tests that evaluate iron metabolism, while molecular assays are needed to document mutations in the HFE gene or others such as hepcidin, hemojuvelin, or transferrin receptor. Individuals with documented iron overload who exhibit signs and symptoms consistent with HH and who possess HFE or other mutations are considered to have HH.
Other causes of secondary iron overload may need to be ruled out. Disorders such as sickle cell disease, thalassemia, sideroblastic anemia, megaloblastic anemia, myelodysplastic syndromes, congenital dyserythropoietic anemia, and liver disease may also cause iron overload. Transfusion-dependant patients and persons who abuse iron-containing vitamin supplements are also at risk. These conditions are usually described as secondary iron overload, in contrast to the primary iron overload of HH. Patient history, clinical signs and symptoms, biochemical and hematologic laboratory analyses, and possibly results of a liver biopsy or bone marrow may be needed to establish a diagnosis of a condition causing secondary iron overload. DNA tests for common HFE mutations are likely the most important diagnostic tool for identifying HH as the cause of iron overload. In some patients, both secondary causes and HH may be contributing to iron overload. Differentiating the secondary causes of iron overload from HH is heavily dependent on the results of laboratory assays.
