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  • Etiologies:

    • Hereditary hemochromatosis (HH)

    • Non-HFE-related hemochromatosis: juvenile HH, other forms

    • Secondary hemochromatosis

  • Most commonly identified genetic disorder in Caucasians

  • Prevalence: 1 per 220 to 250 individuals with Nordic or Celtic ancestry

  • Gender ratio: Men:women: 10:1

  • Gene mutation:

    • Mutation in the HFE gene, C282Y homozygotes, C282Y/H63D, or C282Y/S65C, most frequent mutations

    • Phenotypic expressions only occur in 70% of C282Y homozygotes, and <10% of these subjects will develop severe organ iron overload

    • Juvenile HH: mutations in 2 different genes (hemojuvelin and hepcidin)

    • Other: mutations in the gene for the iron transporter ferroportin

  • Pathophysiology:

    • Increased absorption of dietary iron in the upper intestine

    • Decreased expression of the iron-regulatory hormone hepcidin

    • Altered function of HFE protein

    • Tissue injury and fibrogenesis induced by iron

  • Clinical features

  • Diagnosis (see Fig. 24-1)

    • A combination of transferrin saturation and serum ferritin should be the initial approach

    • Screening: transferrin saturation cutoff >45%

    • Serum ferritin: false-positive rates (inflammatory marker)

    • HFE mutation analysis, including C282Y, H63D, and S65C.

    • A serum ferritin level >1000 ng/L: accurate predictor of liver cirrhosis independent of the duration of the disease

    • Liver biopsy: recommended to stage the degree of disease if liver enzymes are elevated or if ferritin is >1000 ng/mL

  • Management

    • Family screening

    • Average-risk population screening for HH is not recommended

    • Patients with HH and liver cirrhosis should be screened regularly for hepatocellular carcinoma (HCC) via ultrasound every 6 months

    • Vitamin C supplements and iron supplements should be avoided

    • In HH:

      • Early identification and preemptive treatment with phlebotomy

      • Target levels of phlebotomy should be a ferritin level of 50 to 100 µg/L

      • Liver transplantation for decompensated cirrhosis, caution with phlebotomies

    • Secondary hemochromatosis

      • Iron chelation with deferoxamine mesylate or deferasirox

      • Consider follow up with liver biopsy


Hemochromatosis. Liver MRI – T1. A 54-year-old male, HFE gene C282Y mutation +/+ with decompensated cirrhosis on waiting list for liver transplantation. Serum ferritin levels >5500 ng/mL.

TABLE 24-1Symptoms in Patients with Hereditary Hemochromatosis
TABLE 24-2Physical Findings in Patients with Hereditary Hemochromatosis

Wilson Disease

  • First described by Kinnear Wilson in 1912 as “progressive lenticular degeneration”

  • Autosomal recessive ...

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