HFE Hereditary Haemochromatosis - Signs and Symptoms

Signs and Symptoms

Haemochromatosis is protean in its manifestations, i.e., often presenting with signs or symptoms suggestive of other diagnoses that affect specific organ systems. Many of the signs and symptoms below are uncommon and most patients with the hereditary form of haemochromatosis do not show any overt signs of disease nor do they suffer premature morbidity.

The classic triad of cirrhosis, bronze skin and diabetes is not as common anymore because of earlier diagnosis.

The more common clinical manifestations include:

• Fatigue
• Malaise
• Joint and bone pain
• Liver cirrhosis (with an increased risk of hepatocellular carcinoma) Liver disease is always preceded by evidence of liver dysfunction including elevated serum enzymes specific to the liver, clubbing of the fingers, leuconychia, asterixis, hepatomegaly, palmar erythema and spider naevi. Cirrhosis can also present with jaundice (yellowing of the skin) and ascites.
• Insulin resistance (often patients have already been diagnosed with diabetes mellitus type 2) due to pancreatic damage from iron deposition
• Erectile dysfunction and hypogonadism, resulting in decreased libido
• Congestive heart failure, arrhythmias or pericarditis
• Arthritis of the hands (especially the second and third MCP joints), but also the knee and shoulder joints
• Damage to the adrenal gland, leading to adrenal insufficiency

Less common findings including:

• Deafness
• Dyskinesias, including Parkinsonian symptoms
• Dysfunction of certain endocrine organs:
  • Parathyroid gland (leading to hypocalcaemia)
  • Pituitary gland
• More commonly a slate-grey or less commonly darkish colour to the skin (see pigmentation, hence its name Diabetes bronze when it was first described by Armand Trousseau in 1865)
• An increased susceptibility to certain infectious diseases caused by siderophilic microorganisms:
  • Vibrio vulnificus infections from eating seafood or wound infection
  • Listeria monocytogenes
  • Yersinia enterocolica
  • Salmonella enterica (serotype Typhymurium)
  • Klebsiella pneumoniae
  • Escherichia coli
  • Rhizopus arrhizus
  • Mucor species

Males are usually diagnosed after their forties and fifties, and women several decades later, owing to regular iron loss through menstruation (which ceases in menopause). The severity of clinical disease in the hereditary form varies considerably. There is evidence suggesting that hereditary haemochromatosis patients affected with other liver ailments such as hepatitis or alcoholic liver disease suffer worse liver disease than those with either condition alone. There are also juvenile forms of hereditary haemochromatosis that present in childhood with the same consequences of iron overload.