Clinical features

Early stages of hereditary haemochromatosis (HH) are usually asymptomatic.

Symptomatic HH:

• rarely presents in people younger than 40 years
• in women seen after menopause, hysterectomy, or prolonged use of continuous oral contraceptives since blood loss during menstruation delays iron accumulation
• average age at diagnosis is similar for men and women
  • women have less severe disease manifestations
• initial symptoms are often vague and non specific e.g. – weakness, fatigue, lethargy, weight loss, arthropathy in other joints, non-specific abdominal problems, erectile dysfunction, and cardiac problems
  • in a cohort study, around 75% of patients had lethargy and weakness while other patients displayed somnolence, memory disturbances, generalised arthralgia, and reduced libido or impotence in men
• typical presenting symptoms are usually seen in advanced disease and include:
  • diabetes, bronzing of the skin, hepatomegaly, and arthropathy, especially of the second and third metacarpophalangeal joints (1,2,3)

The main tissues which are clinically involved in haemochromatosis include:

• liver
• pancreatic islet cells
• heart
• pituitary
• joints
• skin

Notes:

• variable clinical manifestation of hereditary haemochromatosis:
  • in Northern European populations, the prevalence of C282Y homozygosity is approximately 0.3-0.5%
  • although the majority of male C282Y homozygotes have biochemical changes indicating abnormal iron handling (raised serum ferritin and high transferrin saturation), less than 50% become clinically symptomatic and only a small proportion (probably no more than 10%) develop serious hepatic complications such as cirrhosis or hepatocellular carcinoma
    • it has been suggested than the prevalence of presentation with full-blown clinical manifestations of haemochromatosis may be less than 1%
    • reason why only a small proportion of individuals with a genetic predisposition to hepatic iron overload progress to advanced liver disease is uncertain; in some cases additional environmental cofactors such as alcohol or the metabolic syndrome may be important in unmasking the diseas
  • compound heterozygous state (C282Y/H63D) appears to be more frequent, but is less frequently associated with significant iron overload or liver disease (4)

Reference:

• (1) Bacon BR et al. Diagnosis and management of hemochromatosis: 2011 practice guideline by the American Association for the Study of Liver Diseases. Hepatology. 2011l;54(1):328-43
• (2) van Bokhoven MA, van Deursen CT, Swinkels DW. Diagnosis and management of hereditary haemochromatosis. BMJ. 2011;342:c7251
• (3) Crownover BK, Covey CJ. Hereditary hemochromatosis. Am Fam Physician. 2013;87(3):183-90.
• (4) Hübschera SG. Role of liver biopsy in disorders of iron metabolism.Diagnostic Histopathology 2008; 14 (12): 577-585