Clinical Information

Hemosiderosis is the condition of excessive iron accumulation in tissues. Liver is the first organ affected in iron-overload diseases. Transient increases in iron first appear in Kupffer cells. This finding is commonly related to sideroblastic anemia, excessive iron consumption, or chronic alcohol ingestion. Persistent hemosiderosis, as seen in hemochromatosis, causes iron accumulation in hepatocytes and is usually concentrated in biliary cells.

Hereditary hemochromatosis is an autosomal recessive disease with estimated prevalence of 2 in 1000 in White population, with lower incidence in other races. The gene responsible for hereditary hemochromatosis (HFE) is located on chromosome 6; the majority of patients with hereditary hemochromatosis have variants in the HFE gene. Hereditary hemochromatosis is characterized by an accelerated rate of intestinal iron absorption and progressive iron deposition in various tissues that typically begins to be expressed in the third to fifth decades of life but may occur in children. The most common presentation is hepatic cirrhosis in combination with hypopituitarism, cardiomyopathy, diabetes, arthritis, or hyperpigmentation. Because of the severe sequelae of this disease, if left untreated and recognizing that treatment is relatively simple, early diagnosis before signs or symptoms appear is important.

Screening for hemochromatosis is best done by measuring serum iron and transferrin saturation (FEC / Iron and Total Iron-Binding Capacity, Serum). If the serum iron concentration is above 175 mcg/dL and the transferrin saturation is above 55%, analysis of serum ferritin concentration (FERR1 / Ferritin, Serum) is indicated. A ferritin concentration above 400 ng/mL is suggestive of hemochromatosis but also can indicate other forms of hepatocyte injury, such as alcoholic or viral hepatitis, or other inflammatory disorders involving the liver. HFE analysis (HFET / Hereditary Hemochromatosis, HFE Variant Analysis, Varies) may be used to confirm the clinical diagnosis of hemochromatosis, to diagnose hemochromatosis in asymptomatic individuals with blood tests showing increased iron stores, or for predictive testing of individuals who have a family history of hemochromatosis. The alleles evaluated by HFE gene analysis are evident in approximately 80% of patients with hemochromatosis; a negative report for HFE gene does not rule-out hemochromatosis. In a patient with negative HFE gene testing, elevated iron status for no other obvious reason, and family history of liver disease, additional evaluation of liver iron concentration is indicated.

Diagnosis of hemochromatosis may also be based on biochemical analysis and histologic examination of a liver biopsy. In this assay, results are reported as the hepatic iron index (HII) and dry weight of iron. The HII is considered the "gold standard" for diagnosis of hemochromatosis. This test is appropriate when:

-Serum iron is above 160 mcg/dL

-Transferrin saturation is above 55%

-Ferritin is above 400 ng/mL in male patients or above 200 ng/mL in female patients

-HFE gene test is negative for HFE variants

For more information see Hereditary Hemochromatosis Algorithm.