C2 - hereditary haemochromatosis Flashcards
What is haemochromatosis?
Genetic disorder of iron metabolism
Causes excess deposits in liver, heart, joints, pituaitry, pancrea and skin
What is the key aetiology of hereditary hemochromatosis?
- HFE C282Y mutation on Chromosome 6 - autosomal recessive -> decrease hepcidin
- Considered juvenile when before 30yrs of age - AR - in HJV (Chr1) and Hamp (Chr9)
What are the secondary causes of haemochromatosis?
Dec excretion
Inc intake - dietary supplements
Haemoglobinopathies
Chronic blood transfusions
Why is hereditary haemochromatosis bad?
Iron catalyses formation of free radicals -> inflammation
What investigations are done for heamochromatosis?
Haematinics
Genetics
LFTs, HbA1c, FBC, sex hormones
ECG, exho
What is the role of hepcidin in hemochromatosis?
Related to classic (type 1) disease with mutation in HFE
Reduced hepcidin
Hepcidin normally prevents transport of iron through ferroportin and DMT1 -> this reduced intestinal absorption but also in cellular storage of iron
Leads to increase transferrin saturations and iron remains in blood stream
Leads to hemochromatosis
What are the key signs and symptoms of hereditary hemochromatosis?
Bronze skin
Fatigue
T2DM
Liver disease/cirrhosis -> PHTN
Adrenal insufficienct
Testicular atrophy - erectile dysfunction
Joint pain
Normal range of ferritin is 2.5/3.5g in F/M respectively, symptoms of overload start as 10-20g
What are the key conservative treatments for hereditary hemochromatosis?
Avoid dietary iron and alcohol including iron supplements.
Stage 0 - norm inron studies and no symptoms -> monitor every 3 years
stage 1 - transf saturations above 45%, no symptoms, monitor every 1
What is the medical treatment for hereditart hemochromatosis?
Phlobotomy - stage 3+ - stimulates rbc production to utilise iron
Iron chelation - deforasarox - if anaemic, heart disease or poor access
