{"type":"rich","version":"1.0","provider_name":"Transistor","provider_url":"https://transistor.fm","author_name":"Board Pearls","title":"Chapter 22, Ep 1 of 3: Hereditary Hemochromatosis","html":"","width":"100%","height":180,"duration":578,"description":"Episode one of the Inherited Liver Diseases chapter takes hereditary hemochromatosis and reasons from the molecular lesion outward: lose the HFE signal, lose the hepcidin brake, and iron pours in unchecked for decades. The organizing move is that genotype alone is a substrate, not a disease, so diagnosis rests on biochemistry plus genotype, not a positive C282Y result by itself. Iron regulation, the C282Y and H63D alleles, incomplete sex-skewed penetrance, the two-tier diagnostic framework, phlebotomy to a ferritin target, and the reversibility line all run through the episode. The recurring trap is the healthy homozygote with normal iron studies who is surveyed, not treated.\n \nTopics covered\n\nIron regulation: hepcidin, ferroportin, and HFE\nC282Y and H63D genotypes\nNon-HFE hemochromatosis and ferroportin disease\nBiopsy iron distribution and quantitative thresholds\nIncomplete, sex-skewed penetrance\nCarrier and homozygote frequencies\nDiagnostic criteria and the two-tier framework\nPhlebotomy to a ferritin target\nReversibility, cirrhosis, and HCC surveillance\n \n \nKey decisions\n\nC282Y homozygosity is the classical disease genotype; an isolated H63D allele or compound heterozygosity rarely causes overload and does not warrant phlebotomy or surveillance.\nDiagnose on biochemistry plus genotype: a fasting transferrin saturation of at least forty-five percent in men or forty in women plus a ferritin over three hundred in men or two hundred in women, then HFE genotyping for homozygosity.\nA high ferritin with a normal transferrin saturation in alcohol, fatty liver, or inflammation is secondary hyperferritinemia and is not treated with phlebotomy; treat the upstream driver instead.\nInduction phlebotomy removes about five hundred milliliters of whole blood (roughly two hundred fifty milligrams of iron) weekly to a target ferritin of fifty to a hundred, holding the session if hemoglobin is under eleven.\nHomozygotes with normal iron studies are substrates, not patients, and get...","thumbnail_url":"https://img.transistorcdn.com/-FuAdDBcPDLhEoUmroZKtOBRvuBn_FHPpYlh41hOnU4/rs:fill:0:0:1/w:400/h:400/q:60/mb:500000/aHR0cHM6Ly9pbWct/dXBsb2FkLXByb2R1/Y3Rpb24udHJhbnNp/c3Rvci5mbS9iNzlh/ZTU4Y2MzNWExMjQ5/MjA5OWMwMmI3ZTk5/NGFiZS5wbmc.webp","thumbnail_width":300,"thumbnail_height":300}