Hereditary Haemochromatosis

Introduction

Hereditary haemochromatosis is a genetic disorder whereby inherited mutations in the HFE gene lead to excessive iron absorption and organ dysfunction related to tissue iron overload. The disorder is most commonly seen in individuals of Celtic or Northern European descent. 90% of cases are due to homozygosity for the C282Y mutation, with the majority of the remainder being due to the H63D mutation (although other rarer mutations have also been described).

It is important to note that homozygosity or compound heterozygosity for HFE gene mutations do not guarantee that the affected individual will develop clinical iron overload in their lifetime, and heterozygous carriers of single HFE gene mutations have not been shown to be at risk of developing clinical disease. Homozygotes who develop signs of clinical iron overload overwhelmingly do so in adult life and therefore testing in children is almost never indicated.

Genetic testing of first-degree relatives of known homozygotes is recommended not to be performed before 18 years of age.

If genetic testing has been performed in childhood, there is no need for haematology referral unless:

• there are clinical signs of tissue iron overload
• there is progressive worsening of serum ferritin (>1000 ug/L) with increased transferrin saturation

Pre-referral investigations

• It is recommended that children are not tested for HFE gene mutations before adulthood, even as first degree relatives of patients with known hereditary haemochromatosis
• If a child has nonetheless been tested and found to be heterozygous for an HFE mutation, no further investigation or referral is warranted
• If a child has been tested and found to be homozygous for an HFE mutation (or compound heterozygous for two separate mutations), annual surveillance of iron studies (with specific reference to both transferrin saturation and ferritin) may be considered by the child’s primary care physician
• In the presence of abnormal fasting iron studies, screening biochemistry for end organ function may be considered as appropriate (eg UEC, LFT, TFT, blood glucose)
  • See - Hereditary Haemochromatosis Health Pathway

Pre-referral management

• For homozygotes/compound heterozygotes, annual routine clinical review to screen for potential symptoms of iron overload (e.g. lethargy, arthralgia, liver disease, cardiac failure/dysrhythmia, testicular atrophy)
• Fasting iron studies may be monitored annually, or performed on a PRN basis for clinical concerns
• Parental education and reassurance should be provided regarding the natural history of hereditary haemochromatosis and its clinical onset in middle adult life.

When to refer

• Known homozygous/compound heterozygous HFE mutation carriers only require referral to Paediatric Haematology if there are clinical or biochemical concerns of tissue iron overload; otherwise, referral to adult services after the age of 18 is appropriate.
• Children with a family history of hereditary haemochromatosis do not require referral to Paediatric Haematology, and genetic testing is strongly discouraged before age 18.
• Known heterozygous HFE mutation carriers are not at risk of clinical haemochromatosis and do not require referral to Paediatric Haematology.

How to refer

• Routine non-urgent referrals from a GP or a Consultant are made via the Central Referral Service
• Routine non-urgent referrals from private hospitals are made via the PCH Referral Office (Fax: 6456 0097 or email PCH.Referrals@health.wa.gov.au)
• Urgent referrals (less than seven days) are made via the PCH Referral Office. Please call Perth Children’s Hospital Switch on 6456 2222 to discuss referral with the relevant speciality registrar.

Essential information to include in your referral

• All relevant recent pathology results (serial iron studies, FBP, biochemistry results, any imaging)
• Clinical reason for requesting Paediatric Haematology review.

Useful resources

• Haemochromatosis Australia website
• Hereditary Haemochromatosis Health Pathway

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