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Perth Haematology :: Dr Steven Ward

Haemochromatosis

Haemochromatosis is due to iron overload in many organs and tissues. The features take many years to develop.

Haemochromatosis Brochure (PDF file)

Haemochromatosis assessment

The HFE C282Y and H63D gene mutations are implicated in around 85% of all cases of haemochromatosis. Homozygosity for the C282Y mutation is diagnostic, however the decision to start venesection therapy is based on the degree of iron overload as assessed by serum ferritin and transferrin saturation tests. The significance of the other combinations of these mutations is outlined in the table:

C282Y mutation

H63D mutation

Significance

Homozygous

Normal, homozygous or heterozygous

Diagnostic of Genetic Haemochromatosis.

Degree of iron overload assessed by ferritin and transferrin saturtation (or liver biopsy).

Heterozygous

Heterozygous

H63D mutation in combination with C282Y can lead to iron overload. Again ferritin and transferrin saturation determines degree of loading.

Heterozygous

Normal

Most do not develop iron overload. Occasional person may.

Normal

Homozygous or heterozygous

H63D mutations in isolation are not associated with iron overload.

  

Haemochromatosis – Summary of Features & Complications

Organ System

Features

Reversible with venesection

Frequency

General

Asymptomatic.  A “chance finding” is now the most common presentation since gene testing and more frequent performance of iron studies.  Classical Haemochromatosis features are now uncommon

N/A

Very common Up to 5% of population

Tiredness & arthralgia

Yes

Very common

Liver

Abnormal LFTs (ALT, GGT) – hepatitis

Yes

Common

Cirrhosis and coagulopathy

NO

Rare

Hepatoma

NO

Rare

Pancreas

Diabetes Mellitus

Possibly – or easier to control

Not common

Joints

Arthritis – classically PIPJ of ring and little fingers.

Mostly NO

True arthritis probably rare

Pituitary

Low sex hormone levels, lack of libido

Possibly

Uncommon

Skin

Dark bronzed skin

Possibly

?

Heart

Cardiac failure

Possibly

?

 

Haemochromatosis is now being detected before disease features are present, and certainly well before irreversible end-organ damage has occurred. Regular venesection, usually weekly, to deplete the stored iron is followed by maintenance venesection to keep the ferritin and transferrin saturation low normal. Liver biopsy is now generally reserved for cases with ongoing abnormal LFTs to determine the aetiology and degree of cirrhosis. In cases of uncertainty, with normal gene tests but elevated ferritin and no good inflammatory reason for elevated ferritin (ie normal ESR, CRP, LFTs, fibrinogen level) a trial of venesection is usually carried out to quantify the degree or presence of iron loading. A semi-quantitative assessment of the amount of venesection required to bring the ferritin to 100ug/L is a good indicator of the body iron stores. 

ELEVATED FERRITIN ASSESSMENT FLOW-CHART

Elevated ferritin
M: >400ug/l

F: >200ug/L

F (post-menopause): >300ug/L

Repeat ferritin and transferrin saturation along with inflammatory and acute phase response markers

FBP  & ESR, CRP, LFTs,  coag profile

Resolution or inflammatory cause

Appropriate management of underlying cause

Persisting elevated ferritin ± transferrin saturation without inflammatory cause

HFE gene tests (C282Y & H63D)

 

Haemochromatosis confirmed by gene tests (C282Y homozygous or C282Y and H63D double heterozgyous)

Non-diagnostic gene results (eg isolated H63D mutation)

If abnormal LFTS (raised ALT ± GGT)

Investigate for hepatitis:

Eg: hepatitis B &C, EBV, CMV,  Glucose, USS abdomen Then consider rare disorders

 

Venesection programme & regular clinical review

Trial of vensection

Liver biopsy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Note: The HFE S65C mutation has been discovered but has not been implicated in iron overload.

 

Dr Steven Ward, Clinical Haematologist