Hereditary hemochromatosis

Hereditary hemochromatosis, abbreviated HH, is a genetic (autosomal dominant inherited) cause of iron deposition.

Secondary causes of hemochromatosis are dealt with in secondary hemochromatosis.

General

Epidemiology:

• Genetic defect - HFE gene.
  • One mutation (C282Y mutation) in up to 12.5% of people in populations of northern and central European origin.
  • Homozygotes get the disease.
• Onset in males earlier than females (due to menses).
• Mutation thought to confer survival advantage - several theories (increased resistance to TB, S. typhi vs. decreased iron deficiency/increased iron absorption).

Associated pathology (mnemonic: hemochromatosis can cause deposits anywhere):

• Hypogonadism.
• Cirrhosis and HCC.
• Cardiomyopathy - DCM (esp. with his63asp mutation), may be RCM.
• Diabetes mellitus (bronze diabetes).
• Arthropathy.

Pathophysiology:

• Iron overload -> cirrhosis.

Microscopic

Features:

• Periportal iron deposition (early).
  • Late stage disease has diffuse iron deposition.
• Brown granular - may vaguely look like lipofuscin on H&E.

Notes:

• Iron in the bile ducts and endothelium used to be though specific of hereditary hemochromatosis.
  • It is now thought to just reflect the severity of iron deposition, i.e. if the bile ducts and endothelium have iron - it is severe.

DDx - secondary hemochromatosis:

• Myelodysplastic syndrome.
• Chronic hemolysis.
• Alcoholic liver disease; iron deposition common in cirrhosis.

Images

• 

  Hemosiderosis - iron stain. (WC)

www:

• Hemochromatosis (upmc.edu).

Stains

Iron stain +ve -- important.

• Light blue haze is not enough.
  • Must be separated from siderosis -- iron in Kupffer cells.

Grading

The quantity of iron is scored as follows:

• 0 = none.
• 1: only at high power.
• 2: at medium power.
• 3: at lowest power.
• 4: seen without microscope.

Molecular

• PCR - diagnostic - see molecular pathology tests.

See also

• Medical liver disease.