Practice Easily Missed

Hereditary haemochromatosis

BMJ 2016; 353 doi: https://doi.org/10.1136/bmj.i3128 (Published 30 June 2016) Cite this as: BMJ 2016;353:i3128
  1. Muhajir Mohamed, consultant haematologist and associate professor of medicine1 2,
  2. Jehan Phillips, general practitioner3
  1. 1Department of Medicine, Launceston General Hospital, Tasmania, Australia
  2. 2University of Tasmania, Launceston Clinical School, Launceston, Tasmania, Australia
  3. 3First point Healthcare, Launceston, Tasmania, Australia
  1. Correspondence to: M Mohamed muhajirbm{at}yahoo.com

What you need to know

  • The diagnosis may be missed because symptoms are non-specific, broad, or emerge after the menopause

  • Around one in five cases occur in people who do not fit the northern European stereotype

  • Consider ferritin and transferrin tests to detect to detect iron overload, followed by referral for HFE genetic tests in those with elevated levels

A 38 year old white man presents because of increasing lethargy, excessive sleepiness, and generalised joint pains over the past year, which he attributes to the physical work in his new job. History and examination provide little to suggest a diagnosis. Table 1 shows his basic blood test results.

View this table:
Table 1

Patient’s blood test results

Iron studies showed high values of serum ferritin (1240 μg/L; reference range 30-300) and transferrin saturation (84%; 15-45%). Genetic testing identified a homozygous mutation for C282Y. He was referred to a haematology clinic.

What is hereditary haemochromatosis?

Owen Andersson/ALAMY

Although hereditary haemochromatosis is thought to be an autosomal recessive disorder in people of northern European ancestry, about a fifth of cases are atypical, and various mutations are described outside the northern European stereotype. Mutations in the HFE gene on chromosome 6 and non-HFE mutations predispose to increased intestinal iron absorption and iron overload. Clinical manifestations are related to iron deposition in organs such as the liver, pancreas, joints, skin, and heart, with the production of free radicals, which have toxic effects at the cellular level.1

Symptoms usually start during the fourth or fifth decade of life.2 Iron overload is uncommon in women of childbearing age because of blood loss during menstruation, so women usually present after menopause. Regular blood donation reduces the likelihood of developing symptoms.

The genetics of haemochromatosis are complex (box 1). The most common mutation associated with iron overload is C282Y homozygous (p.Cys282Tyr). The homozygous H63D mutation and compound heterozygosity (C282Y/H63D) are …

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