Gastrointestinal · Year 2 · from Gastrointestinal
Case 3: Hemochromatosis (Iron Overload)
Patient Presentation
Demographics: 52-year-old male of Northern European descent
Chief Complaint: Fatigue, joint pain, and elevated liver enzymes
History of Present Illness: The patient was found to have elevated liver enzymes (AST 68, ALT 82) on routine bloodwork. He reports progressive fatigue for 2 years and joint pain, particularly in the second and third metacarpophalangeal joints bilaterally. He has also noticed decreased libido. His wife comments that his skin has become "bronzed" despite limited sun exposure.
Past Medical History: Recently diagnosed with type 2 diabetes (6 months ago), atypical for his body habitus
Family History: Father died of liver disease at age 58; brother has "iron problems"
Physical Examination
- Vital Signs: Normal
- General: Bronze/slate-gray skin discoloration
- Abdomen: Hepatomegaly (liver palpable 4 cm below costal margin), non-tender
- Musculoskeletal: Tenderness and bony swelling of 2nd and 3rd MCP joints bilaterally
- Genitourinary: Testicular atrophy
Workup and Results
- Iron Studies: Serum iron 285 mcg/dL, TIBC 290 mcg/dL, transferrin saturation 98% (markedly elevated), ferritin 2,850 ng/mL
- Liver Function: AST 68, ALT 82, ALP normal, albumin 3.4
- HFE Gene Testing: Homozygous for C282Y mutation
- Liver MRI: Hepatic iron overload (signal loss on T2-weighted images)
Prussian blue staining of liver biopsy showing extensive blue-staining iron deposits within hepatocytes, characteristic of hereditary hemochromatosis.
Image Source: Wikimedia Commons, Public Domain
Diagnosis
Hereditary Hemochromatosis (HFE-related)
Clinical Correlation to Iron Absorption Physiology
Iron absorption is tightly regulated because humans have no mechanism for iron excretion. Dietary non-heme iron is reduced by DcytB at the brush border and transported into enterocytes by DMT1. Iron can be stored in ferritin within the enterocyte (lost when the cell sloughs) or exported across the basolateral membrane via ferroportin. Hepcidin, produced by the liver, is the master regulator - it binds ferroportin and causes its degradation, blocking iron export. In HFE-related hemochromatosis, the C282Y mutation impairs hepcidin signaling, resulting in inappropriately low hepcidin levels. Without adequate hepcidin, ferroportin activity is unchecked, and iron absorption continues regardless of body stores. Iron accumulates in the liver (cirrhosis), pancreas (diabetes), heart (cardiomyopathy), pituitary (hypogonadism), joints (arthropathy), and skin (bronze discoloration).
Treatment
- Therapeutic phlebotomy: weekly removal of 500 mL blood (containing ~250 mg iron) until ferritin <50 ng/mL
- Maintenance phlebotomy every 2-4 months to keep ferritin 50-100 ng/mL
- Avoid vitamin C supplements (enhances iron absorption)
- Avoid excessive alcohol (worsens liver disease)
- Screen first-degree relatives with HFE genetic testing
- Diabetes and hypogonadism may not resolve but can be managed
- Liver transplantation for end-stage liver disease