Hereditary Haemochromatosis

Last updated 26.09.12

 

Definition

- Inappropriately high absorption of dietary iron leading to accumulation in organs & toxicity

 

Features

- Most common inherited liver disease in Caucasians

-  Prevelance 1:300 Caucasians

-  10% carrier rate

- Most common autosomal recessive genetic disorder

-  HFE gene (chromosome 6)

-  HFE1 C282Y mutation 82-90%  

- HFE2A (Hepcidin), HFE2B (Hemojuvelin) & HFE3 (Transferrin Receptor 2) )also possibly effected

- Adult onset, typically > 40 yrs

-  Takes many years to develop

-  Average age of onset

-  Men 50yrs+

-  Women 60yrs+

- Men1:1 women but typically women who menstruate less likley to develop iron overload

- Iron deposits in heart, liver, pancreas, pituitary, joints, skin

- Bronzed diabetic

- Should be screened in patients with

-  First degree releative with haemochromatosis

-  Abnormal LFTs or Iron studies

 

DDx

-  Neonatal Haemochromatosis

- Secondary Iron Overload

 

Associated S/S

-  Symptoms from iron overload

-  Early symptoms

-  Fatigue

-  Hypogonadism: impotence, decreased libido, amenorrhoea

-  Arthralgia

-  MCP, PIP, knees, feet, wrists, back

- Joint swelling & tenderness

-  Hepatomegaly 13%

-  Cirrhosis

-  Most common cause of death

-  Most common disease manifestation

-  May progress to HCC

-  Screen with AFP & ultrasounds every 6/12

- Testicular atrophy

-  Heart failure

-  CCF or arythmias (cardiomyopathy)

-  Dilated cardiomyopathy

-  Cardiomegaly

-  DM2 50%

-  Bronzed skin 70%

-  Hypothyroidism: rarely

-  Porphyria cutanea tarda

 

Ix

- FBE

- + Blood film: anaemia

-  Hb: anaemia

- Determine level prior to venesection

-  Iron Studies

-  Ferretin

-  > 300 men

-  > 200 women

-  > 1000 indicates pathology likely esp cirrhosis

- Measuring after an overnight fast decreases the effects of diurnal variation of serum iron

-  Transferin Saturation

-  Initial test of choice

- If >45% suggestive of iron overload

-  Aim for <45% when treating

-  Highly specific

-  30% women < 30 yrs = normal

-  Iron: little Dx use

-  LFTs: hepatitic (ALT, AST) = cirrhosis, HCC

-  Albumin, INR

-  Genetic studies

-  HFE gene with C282Y & H63D mutations in patient, 1st degree relatives

-  C282Y

-   Homozygote = Dx (majority of cases, 60-90%)

-   Heterozygote = not Dx

-   Responsible for most of disease

-  Compound heterozygote C282Y/H63D = Dx

-  H63D heterozygote = not Dx

-  S65C : typically not associated with significant iron overload

-  Liver biopsy: for patients with high probablily of cirrhosis

-  Homozygote C282Y, Ferretin >1000 & abnormal LFTs

-  BSL: DM2

-  TTE: cardiomyopathy

-  TFT: hypothyroidism

 

Mx

-  Regular phlebotomy/venesection

-  500ml weekly until Ferretin

- Initially test Hb second weekly & Ferretin monthly

- If Hb <110 or Ferretin 20-50mcg/L then reduce frequency

-  Then 3/year to maintain Ferretin <100mcg/L

- Test Ferretin 6 monthly

-  Reduces morbidity

-  Less effect on gonadal symptoms

- Australian Red Cross Blood Service online application for Venesection

- Consider Desferrioxamine chelation therapy if cannot tolerate venesection ($$)

- Non-cirrhotic patients who are Dx & treated early have a normal life expectancy

-  Dietary Considerations

- Avoid iron supplemention

-  Reduce/eliminate EtOH: abstinence not required unless cirrhosis

-  Avoid raw oysters: V vulnificus may cause sepsis

-  Liver transplant: end stage liver disease, HCC

-  Arthroplasty: joint destruction

- Screening

- Screen siblings

- Screen homozygotes for C282Y with iron studies every 2-3 years

 

 

 

References

 

BU General Internal Medicine Grand Round: Hemochromatosis, Robert Lowe

GESA: Haemochormatosis 2007

How to Treat: Hereditary Haemochromatosis

Haemochromatosis Australia