Genomics in general practice

Hereditary haemochromatosis

Last revised: 30 Nov 2018

Practice point

Hereditary haemochromatosis (HHC) is a common condition that affects an estimated one in 250 individuals of northern European backgrounds. Genetic testing for HHC should be performed in patients with proven iron overload. Cascade screening of relatives is also important when specific gene variants causing HHC are confirmed in the family.1

Screening for HHC in the general population is currently not recommended given its variable expressivity and incomplete penetrance.2,3
 

HHC is a condition with an autosomal recessive inheritance pattern where excessive iron absorption leads to increased blood iron stores. HHC is underdiagnosed as the symptoms are usually non-specific; however, early diagnosis and treatment reduces serious complications and possible early death.

The most common genetic cause of HHC (up to 90%) is homozygosity of the C282Y gene variant in the HFE gene (HFE-haemochromatosis). About one in 10 people are carriers of a C282Y variant, while one in every 200 carriers is homozygous for the C282Y variant. Another common variant in the HFE gene is H63D. Not all individuals with a genetic predisposition to HHC will develop iron overload (incomplete penetrance).2

The risk of iron overload varies according to genotype (Table 1).3–5

Table 1. Varying genotypes and risk of iron overload

Table 1

Varying genotypes and risk of iron overload

Genetic testing for the risk of HHC is recommended in individuals with suspected iron overload (ie elevated serum ferritin concentration >200 µg/L [(females)] or >300 µg/L [(males)], and a transferrin saturation >45% will identify almost all patients with HFE-haemochromatosis).2,6–8

Cascade screening is warranted for all first-degree relatives of patients with HHC who are C282Y homozygous or C282Y/H63D compound heterozygous.

A Medicare Benefits Schedule (MBS) rebate for the HFE gene test applies where the patient has an elevated transferrin saturation or elevated serum ferritin on repeat testing or a first-degree relative with haemochromatosis or is homozygous for the C282Y gene variant or a compound heterozygote.9

Asymptomatic individuals (identified through cascade screening) who are C282Y homozygous or C282Y/H63D compound heterozygous should have their serum ferritin regularly monitored.2,6

Patients with HFE-haemochromatosis should be encouraged to:8

  • inform all first-degree relatives of increased risk
  • direct family to information about haemochromatosis (eg Haemochromatosis Australia)
  • advise family members to discuss their risk with their general practitioner (GP).

Seckington R, Powell L. HFE-associated hereditary haemochromatosis. GeneReviews. Seattle, WA: University of Washington, 2000

Information

Centre for Genetics Education, Fact sheet 47: Hereditary haemochromatosis
National Library of Medicine (US), Hereditary hemochromatosis

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