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HH vs Wilson Disease




General Features


  • Hereditary hemochromatosis: disorder of iron overload
  • Accumulation of iron resulting in toxicity of the liver, pancreas, joints, skin, heart, and endocrine organs
  • Wilson disease (hepatolenticular degeneration): disorder of copper overload
  • Accumulation of copper resulting in toxicity of the liver, kidneys, brain, eyes, heart, and red blood cells
  • Both hereditary hemochromatosis and Wilson disease are inherited, autosomal recessive disorders that can cause cirrhosis due to excess metal accumulation
  • Hereditary hemochromatosis: mutation in the HFE gene
  • Common mutations: C282Y and H63D
  • Wilson disease: mutation in the ATP7B gene
  • The liver is the main organ affected by excess of both metals, but the mechanism of metal accumulation and overload differs
  • Hereditary hemochromatosis: the liver receives excess iron
  • The intestinal mucosa absorbs excess amounts of dietary iron which is received passively by the liver
  • Wilson disease: the liver accumulates excess copper inside liver cells
  • Liver cells have an impaired ability to excrete copper into bile
  • There is also impaired binding of copper to ceruloplasmin

Clinical Features and Diagnosis


  • Patients may be asymptomatic
  • Hereditary hemochromatosis: hepatic fibrosis or cirrhosis, arthritis, diabetes mellitus, skin pigmentation (“bronze diabetes”), loss of libido/impotence, cardiomyopathy, and other endocrine disorders
  • Elevated fasting serum transferrin saturation greater than 45-50%, ferritin greater than 300 ng/mL in men and greater than 200 ng/mL in women, and increased iron
  • HFE gene testing
  • Liver biopsy may be helpful in determining the degree of fibrosis
  • Imaging studies such as CT and particularly MRI may detect heavily iron-loaded individuals, but are not reliable methods to make the definitive diagnosis
  • Wilson disease: cirrhosis, chronic hepatitis, fulminant hepatic failure, neuropsychiatric disorders, Kayser-Fleischer rings, renal disease, hemolytic anemia, cardiomyopathy
  • Elevated serum copper, low serum ceruloplasmin less than 20 mg/dL (but can be normal), and elevated 24-hour urinary copper greater than 100 μg/day
  • Liver biopsy should be performed for quantitative measurement of hepatic copper

Treatment


  • Hereditary hemochromatosis: phlebotomy (weekly or biweekly) until ferritin level is less than 50 ng/mL and the transferrin saturation is less than 50%, followed by life-long maintenance phlebotomies every 2 to 4 months once excess iron stores are removed
  • Wilson disease: decrease dietary copper, copper-chelating agents such as d-penicillamine or trientine, oral zinc supplementation (interferes with copper absorption in the GI tract), liver transplant for end-stage disease
  • Family screening for all first-degree relatives (both hereditary hemochromatosis and Wilson disease)