Hemochromatosis

Etiology

  • Autosomal recessive disorder of dysregulated iron absorption
  • Majority related to mutation in HFE gene, which regulates hepcidin; decreased hepcidin results in unregulated iron absorption and overload
  • Multi-site organ dysfxn occurring after decades due to iron deposition
  • Less common mutations can also cause iron overload: e.g. affecting transferrin receptor protein or ferroportin (promotes iron movement from cells into blood)
  • Secondary iron overload can occur w/Thalassemia or other disorders leading to hemolysis, frequent transfusions, other

Risk Factors

  • Family hx
  • M > f
  • European ancestry
  • Typically asymptomatic until age >50

Symptoms

  • Degree of symptoms varies if coexisting liver dz (e.g. etoh, hep c, nafld)
  • Sx develop based on organs affected: decreased libido and impotence→ testicular dysfxn
  • Infertility/menstrual irregularity→ ovarian dysfxn
  • Jaundice/ascites/liver cancer→ cirrhosis
  • Symmetric joint pain and swelling, in particular MCPs→ arthropathy
  • Diabetes→ pancreas
  • Iron deposition in skin-→ dark skin
  • Head ache/visual sx/fatigue→ pituitary, hypothalamus
  • Sob, fatigue, edema → dilated cardiomyopathy, conduction system disease

Physical Exam Findings

  • Dark skin
  • Small testes
  • Findings of Chf
  • Hepatomegaly, spider angiomata, palmar erythema (stigmata chronic liver dz); jaundice and ascites if advanced disease/cirrhosis
  • Symmetric arthritis MCPs, other joints

Tests

Links