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Training & Education - Clinical Features

Clinical Expression

Many factors contribute to the clinical expression of hemochromatosis:

  • Rate of iron absorption.
  • Age. The majority of cases are recognized in midlife, when body iron stores have accumulated.
  • Gender. Onset in males is usually earlier than in females, who may be at lower risk due to pregnancies and menstrual blood losses.
  • Dietary influences.
    • Iron supplements can accelerate iron accumulation.
    • Alcohol consumption contributes to cirrhosis of the liver.
    • Vitamin C increases iron absorption.
  • Iron losses. Loss of iron from other processes (blood donation, menstruation, occult bleeding, pregnancy) may delay onset.
  • Presence of other diseases or toxins.
  • Modifier genes.

The iron accumulation rate and the frequency and severity of clinical symptoms vary widely. Most patients may have no early symptoms. Little is known about the time from iron loading onset to development of symptoms or injury to body organs.

Early Stages of Hemochromatosis

Hemochromatosis symptoms are non-specific and seldom by themselves suggest a hemochromatosis diagnosis.

The most commonly associated early hemochromatosis symptoms may include:

  • Fatigue.
  • Weakness.
  • Weight loss.
  • Abdominal pain.
  • Arthralgia.

If a patient presents with non-specific symptoms and uncertain etiology, consider a hemochromatosis workup.

As iron accumulation progresses, patients may also experience:

  • Arthritis.
  • Symptoms of gonadal failure.
    • For example, amenorrhea, early menopause, loss of libido, impotence.
  • Shortness of breath/dyspnea.

Clinical Course of Hemochromatosis

illustration of symptoms of iron accumulation over time
Early hemochromatosis symptoms are non-specific. However, as iron accumulation increases over time, more advanced complications occur.

Advanced Stages of Hemochromatosis

Iron accumulates in the parenchymal cells of several organs; the liver is a major site, followed by the heart and pancreas.

Conditions associated with advanced stages of hemochromatosis include:

  • Arthritis.
  • Abnormal liver function (e.g., elevated transaminase and clinical liver disease).
  • Glucose intolerance and diabetes.
  • Chronic abdominal pain.
  • Severe fatigue.
  • Hypopituitarism.
  • Hypogonadism.
  • Cardiomyopathy and arrhythmia.
  • Cirrhosis.
  • Liver cancer.
  • Heart failure.
  • Gray or bronze skin pigmentation.

Primary Disorders Associated with Advanced Hemochromatosis

Most advanced hemochromatosis complications are also common primary disorders. A hemochromatosis diagnosis can be missed even in advanced stages unless looked for specifically (Hanson EH, 2001). Some complications are not clearly related to excess iron, yet, when excess iron is removed, many patients report feeling better.

The liver is usually the first affected organ. Hepatomegaly is one of the most frequent findings at clinical presentation, followed by cirrhosis. Primary hepatocellular carcinoma is more common in hemochromatosis patients with cirrhosis than in the general population (Haddow JE 2003; Niederau C, 1985; Willis G 2000).

Diabetes mellitus occurs in 25–75% of patients. It is more likely to develop in those with family histories of diabetes, suggesting that direct damage to pancreatic islets by iron deposition occurs in combination with a genetic predisposition.

Arthropathy develops in 25–50% of patients. It usually occurs after age 50.

Cardiac involvement is the presenting manifestation in about 15% of patients. The most common manifestation is palpitations as symptoms of arrhythmia.

Hypogonadism occurs in both sexes and may antedate other clinical features. Manifestations include loss of libido, impotence, amenorrhea, testicular atrophy, gynecomastia, and sparse body hair.

Excessive skin pigmentation is present in more than 90% of symptomatic patients at diagnosis.

Note: See Barton JC (1998) for more in depth information about the clinical stages of hemochromatosis.