GP information for common genetic conditions

Genetic Haemochromatosis

Genetic Haemochromatosis (GH) is a common genetic disorder that causes excess iron absorption.

Over time, if untreated, this can lead to liver damage, joint problems, and/or endocrine problems.

Treatment is simple and effective and usually consists of venesection to remove excess iron.

Generally adult onset, affecting both men and women (mean onset age 45-50 years in men and 50-60 years (post menopause) in women).

Monthly menstrual cycle is protective in pre-menopausal women.

Early signs are usually non-specific, including fatigue and lethargy.

GH associated with HFE gene common alterations

Inheritance is Autosomal Recessive.
Around one in nine in the North European population are carriers.
Carriers (HFE gene C282Y heterozygous or H63D heterozygous) do not usually develop symptoms of GH.
HFE gene H63D homozygotes - it is unusual for these individuals to develop problems with iron overload.
HFE gene C282Y homozygote (YYHH) or C282Y/H63D compound heterozygote (CYHD) - these patients are at risk for iron overload.

Treatment and management

Asymptomatic patients with HFE C282Y homozygous results should have their serum ferritin and transferrin saturation levels monitored annually and be referred to hepatology for baseline assessment.

Asymptomatic patients with HFE C282Y/H63D results should have their serum ferritin and transferrin saturation levels monitored three yearly and be referred to hepatology for baseline assessment.

Alcohol reduction should be emphasised.

Otherwise fit and well individuals can be encouraged to become regular blood donors with NHS Blood and Transplant's Blood Services.

Young children are unlikely to be clinically affected. Unless they are presenting with clinical symptoms, there is no indication for genetic testing children until they are old enough (>18yrs) to understand the implications themselves.

If a patient has a negative result on the HFE gene test but has persistently raised iron and/or ferritin levels, there could be another cause for this. A broader gene panel could be considered.

Currently this can only be requested following review by specialist services. Please contact Hepatology for advice and guidance.

Prenatal diagnosis

Testing in pregnancy is not usually offered to carrier parents, as it is most often an adult-onset treatable disorder.

Resources

Ordering the test

This guidance is for ordering genetic testing for Genetic Haemochromatosis (the common HFE genotypes).

Please complete the form below to request Genetic Haemochromatosis testing for your patient.

Oxford Genetics Laboratories - request form

Complete the 'Patient details' section with your patient's details.

Complete the 'Referrer details' section with your own details.

Complete the 'Clinical details and family history' section with relevant details regarding the need for Genetic Haemochromatosis testing (e.g. patient has a family history of Genetic Haemochromatosis with X relative being affected with the condition).

In the sample requirements section please tick: '1-5ml venous blood sample in an EDTA tube'.

Please indicate the patient's fasting serum ferritin and transferrin saturation levels, if known.

If patient has had a bone marrow transplant, email the laboratory for saliva test kit

Email: haemostasis-iron.oxfordgenetics@ouh.nhs.uk

In the 'Tests requested' box please write 'HFE genotyping. (R95)'.

The sample can be dispatched to the lab via your usual GP specimen route.

Important: both sides of the blood form (front and back) are required and it should be printed double-sided.

Turnaround time

42 calendar days from receipt of sample and all the required information.

Results

The laboratory will send the result directly to you to give to your patient.

Result interpretation

Possible results

Patient is an GH carrier (heterozygous)

Carriers do not usually have the medical problems associated with haemochromatosis.

To clarify the risk to any young children, partners of a carrier may wish to consider carrier testing themselves via their GP.

Adult children (age 18+) can seek their own genetic testing via their GP if they wish to.

Patient is at risk for GH (homozygous or compound heterozygous)

If your patient is a C282Y homozygote (YYHH) or a C282Y/H63D compound heterozygote (CYHD) please refer to local hepatology unit for baseline assessment. It has been difficult to determine the true incidence of the condition as some individuals with the genetic alterations do not develop symptoms of the disorder.

Asymptomatic patients with C282Y homozygous results should have their serum ferritin and transferrin saturation levels monitored annually.

Asymptomatic patients with C282Y/H63D compound heterozygous results should have their serum ferritin and transferrin saturation levels monitored three-yearly.

Close adult (age 18+) relatives (children, parents, siblings) of a patient with a homozygous or compound heterozygous GH result, are eligible for genetic testing for Genetic Haemochromatosis themselves and can book in with their GP to arrange genetic testing if they wish to.

Children are unlikely to be symptomatic, even if they have the condition. Unless they are presenting with clinical symptoms, there is no indication for testing children until they are old enough (>18yrs) to understand the implications themselves.

Result negative but no explanation for raised iron levels

If a patient has a negative result on the HFE gene test but has persistently raised iron and/or ferritin levels, there could be another cause for this. A broader gene panel could be considered.