0226 - Haemochromatosis Flashcards
What is transferrin? What is transferrin saturation?
Transferrin is an iron transport protein. Inverse relationship with ferritin (so synthesis stopped as iron levels rise).
Transferrin saturation is the % saturation on all available transferrin binding sites >50% in haemochromatosis.
What is ferritin?
An iron storage protein - protects body from accumulation of iron. Synthesis is induced by elevated iron levels. Present in most tissues and serum.
Why is serum iron not an effective measure of iron levels?
Most iron is stored in ferritin, and transported by transferrin. Elevated ferritin and/or transferrin saturation are a more valuable diagnostic tool than serum iron.
What is hepcidin?
Iron regulatory hormone, synthesis stimulated by iron and inflammation.
Negatively regulates iron absorption, transport out of macrophages, and across placenta.
Iron levels go up, hepcidin switches on, tells the iron to not get absorbed. In haemochromatosis, key pathogenetic feature is insufficient production of hepcidin relative to iron levels.
Briefly outline iron metabolism - KEY EXAM CONCEPT
Male needs 1mg/day, female 1.5. Dietary intake of 5-10mg/day due to poor absorption.
Used for haemoglobin, myoglobin, cytochrome P450, and by the immune system. Daily requirements are small, to replace losses, but there is no mechanism to excrete excess iron.
Define haemochromatosis.
The excessive accumulation of body iron, most of which is deposited in the paranchymal cells of various organs, particularly liver and pancreas.
Key pathogenetic feature is insufficient production of hepcidin relative to iron levels.
Briefly outline haemochromatosis
Excess body iron deposited in parenchyma of various organs (liver and pancreas). Minimal symptoms, few signs, and these days detected by raised ferritin on LFTs.
HFE haemochromatosis is major type, mostly caused by recessive C282Y and/or H63D mutations, but low penetrance.
Key pathogenetic feature is insufficient production of hepcidin relative to iron levels.
How do you detect and diagnose haemochromatosis?
Best to look at serum ferritin, if raised in conjunction with transferrin saturation (<50%). If in doubt, liver biopsy for increased hepatic iron.
Also test for HFE mutations.
What is the genetics of haemochromatosis?
Autosomal recessive disease.
Abnormality found on the HFE gene, chromosome 6p. Homozygous C282Y gives haemochromatosis, or occasionally H63D homozygous.
What is the penetrance of haemochromatosis?
Penetrance is low - 28% C282Y homozygous males had iron-overload related disease, and 1.2% females (menstruation?).
When do you treat haemochromatosis? What happens if untreated?
Regular phlebotomy (venosection) until serum ferritin is low-normal. If untreated, cirrhosis, hepatocellular carcinoma, and cardiac disease.
