Body Handbook Catalogue Profile Ranking
Screening BODY HANDBOOK
Screening ยท ยง120
HFE Hemochromatosis
If you're of Northern European descent, especially Irish, Scottish, or Welsh, there's a 1-in-200 chance you inherited two broken copies of a gene called HFE and your gut has been over-absorbing iron for life. It piles up silently for decades, then wrecks the liver, joints, heart, and pancreas in your 50s and 60s. The tell is that early on it just looks like ordinary middle-aged decline. Two cheap blood numbers catch it, and caught before the liver scars, your lifespan is completely normal.
Condition Evidence Moderate Chapter Screening

The defect is a stuck iron thermostat. A liver hormone, hepcidin, shuts off iron absorption when stores are full; HFE is part of the sensor that trips it. With two broken copies the sensor reads "empty" forever, and the gut keeps pulling in iron the body doesn't need 1. Almost all serious cases trace to one change, C282Y: 1 in 9 Northern Europeans carries a copy, 1 in 200 carries two 2.

The overload is silent until it isn't. Untreated men with two C282Y copies reach roughly 7% lifetime risk of liver cancer by 75, against under 1% otherwise, about 10 times the general risk 3. Around 1 in 5 develop diabetes, 2 in 5 develop arthritis bad enough to see a doctor 4. Women run about a third of these risks, because periods and pregnancy bleed iron out 5.

The treatment deal is one of the cleanest in medicine. Drain the iron before the liver scars and survival matches people who never had the gene; arrive with cirrhosis already and 10-year survival is about 50% 6, 7. The whole game is timing.

This is a testing decision, and it starts with two blood numbers, not a gene test. The gene test only comes after both numbers run high.

The arc runs on months, then decades. In the first month or two the afternoon heaviness lifts and liver enzymes trend back to normal. By month six ferritin crosses below 100 ng/mL and the weekly visits thin to a few a year. Grey-bronze skin un-shifts over six to twelve months; sex drive returns if the pituitary wasn't already damaged. The big payoff is invisible and permanent: the cirrhosis, diabetes, and liver cancer you'd have met in your 60s simply never arrive 6, 7.

The fine print โ€” when to skip it, and what people get wrong

If you have it: no raw shellfish, oysters especially, since Vibrio vulnificus feeds on iron and can turn one into fatal sepsis 9. Skip iron supplements, and cap alcohol, which lowers the load at which the liver scars 2.

Diet can't fix established overload: it gives 1โ€“2 mg of iron a day, one phlebotomy removes 200โ€“250 11. A positive 23andMe usually flags one copy, which is not the disease; diagnosis is the genotype plus loaded iron 12.

Checking ferritin alone misses it: infection and fatty liver raise ferritin, and early cases show high saturation with normal ferritin, so test both 8. Stopping maintenance once you feel well re-accumulates iron over years 6.

References
  1. 1Feder JN, Gnirke A, Thomas W et al. (1996). A novel MHC class I-like gene is mutated in patients with hereditary haemochromatosis. Nature Genetics. link
  2. 2Powell LW, Seckington RC, Deugnier Y (2016). Haemochromatosis. The Lancet. link
  3. 3Atkins JL, Pilling LC, Masoli JAH et al. (2020). Association of hemochromatosis HFE p.C282Y homozygosity with hepatic malignancy. JAMA. link
  4. 4Pilling LC, Tamosauskaite J, Jones G et al. (2019). Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank. BMJ. link
  5. 5Allen KJ, Gurrin LC, Constantine CC et al. (2008). Iron-overload-related disease in HFE hereditary hemochromatosis. New England Journal of Medicine. link
  6. 6Niederau C, Fischer R, Purschel A et al. (1996). Long-term survival in patients with hereditary hemochromatosis. Gastroenterology. link
  7. 7Adams PC, Speechley M, Kertesz AE (1991). Long-term survival analysis in hereditary hemochromatosis. Gastroenterology. link
  8. 8Kowdley KV, Brown KE, Ahn J, Sundaram V (2019). ACG clinical guideline: hereditary hemochromatosis. American Journal of Gastroenterology. link
  9. 9Bacon BR, Adams PC, Kowdley KV, Powell LW, Tavill AS (2011). Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. link
  10. 10European Association for the Study of the Liver (2022). EASL clinical practice guidelines on haemochromatosis. Journal of Hepatology. link
  11. 11Adams PC, Barton JC (2010). How I treat hemochromatosis. Blood. link
  12. 12Beutler E, Felitti VJ, Koziol JA et al. (2002). Penetrance of 845Gโ†’A (C282Y) HFE hereditary haemochromatosis mutation in the USA. The Lancet. link
Related in the handbook (5)
Detected by
  • โ€” Ferritin and transferrin saturation are the cheap blood tests that flag the iron overload before it scars anything.
Related
  • โ€” HFE hemochromatosis is a textbook case where a genetic test changes what you do.
  • โ€” The reason to test before supplementing: in hemochromatosis, extra iron speeds a slow poisoning.
  • โ€” Ferritin is the shared dial: too high points here, too low points the other way. Same test, opposite problems โ€” know which side you're on.
  • โ€” Iron overload and fatty liver are the two common roads to a scarred liver โ€” and they read on the same liver panel, sometimes together.
ยท
120