Hereditary haemochromatosis most commonly results from which mutation, and which HFE genotype accounts for the majority of cases in Northern European populations?
- A C282Y/C282Y homozygous HFE mutation ✓
- B H63D/H63D homozygous HFE mutation
- C C282Y/H63D compound heterozygous HFE mutation
- D SLC40A1 (ferroportin) mutation
Explanation
HFE-related hereditary haemochromatosis (HH) type 1 accounts for >90% of cases in Northern European populations, with C282Y/C282Y homozygosity responsible for ~85% of clinically significant iron overload. The C282Y mutation (missense Cys282Tyr on chromosome 6p) disrupts HFE protein interaction with transferrin receptor, impairing hepcidin signalling, leading to unrestricted dietary iron absorption. H63D/H63D homozygosity rarely causes clinical iron overload. Compound heterozygotes (C282Y/H63D) cause mild-moderate iron loading. Ferroportin mutations (SLC40A1) cause a distinct type 4 haemochromatosis.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.