Hereditary hemochromatosis is an inherited disorder, most often from two copies of the C282Y variant of the HFE gene, in which the gut absorbs too much iron that builds up in the liver, heart, pancreas, joints and skin. It is most common in people of Northern European descent, and men show signs earlier than women, who lose iron through periods and pregnancy.
Key symptoms
- Fatigue and weakness
- Joint pain, especially in the second and third knuckles
- Low libido, erectile dysfunction or missed periods
- Bronze or darker skin; thirst and frequent urination from diabetes
- Often found on routine labs without symptoms
What you find on exam
- Enlarged liver and signs of cirrhosis such as spider angiomas, jaundice and ascites
- Bronze or gray skin color
- Swollen, tender second and third knuckles
- Small testicles; signs of heart failure or irregular rhythm
Tests
- Transferrin saturation above 45% and a high ferritin
- HFE gene testing for C282Y and H63D
- Liver tests; check for fibrosis if ferritin is over 1000 ng/mL or liver tests are abnormal
- MRI to estimate liver iron; glucose or HbA1c, ECG and echocardiogram
Treatment basics
- Therapeutic phlebotomy, about 500 mL weekly, until ferritin is about 50 to 100 ng/mL, then maintenance
- Iron chelation with deferoxamine or deferasirox if phlebotomy is not possible
- Avoid iron and vitamin C supplements and raw shellfish; limit alcohol
- Screen first-degree relatives
- Liver cancer surveillance with ultrasound every 6 months if cirrhosis is present
Red flags
- Signs of cirrhosis: jaundice, ascites, confusion or bleeding
- Heart failure or a new irregular rhythm
- Severe illness after raw shellfish or a wound in sea water (Vibrio infection)
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Sources: NCCPA PANCE Content Blueprint; NBOME COMLEX-USA clinical presentations; AAMC Core Entrustable Professional Activities (Core EPAs). Written by Making Synapses. Making Synapses is not affiliated with these organizations.