Hemochromatosis Symptoms and Diagnosis

hemochromatosis symptoms hyperpigmentation

Hemochromatosis is a condition resulting from an excess of iron in the body. It can be a primary disorder that is hereditary and runs in families or secondary to excess iron ingestion and repeated blood transfusion. Symptoms of hemochromatosis may be subtle and may take months to years before the diagnosis is made.

Iron-overload conditions other than hereditary hemochromatosis:

Secondary hemochromatosis is much more common than hereditary hemochromatosis. It is commonly seen in patients who get regular transfusions.

Patients who require regular transfusion include:

  • Hemolytic anemias like thalassemia, hereditary spherocytosis, and pyruvate kinase deficiency.
  • Some patients with aplastic anemia.

Thalassemia hemochromatosis

Other causes of  iron excess in the body include:

  • Use of iron utensils for cooking
  • Porphyrias
  • Sideroblastic anemia
  • Congenital dyserythropoietic anemias

Hemochromatosis symptoms and diagnosis

The clinical manifestations of hemochromatosis depend on the degree of iron deposition and organ involved.

Iron commonly deposits in the liver, kidneys, endocrine glands like pituitary, pancreas, thyroid, parathyroid gland, gonads, skin, and the joints.

Liver disease in hemochromatosis:

The Liver is probably the most common organ involved in patients with hemochromatosis. Individuals may develop an enlarged liver that may be associated with right upper abdominal pain, and abnormal liver enzymes (ALT and AST).

This is followed by progressive fibrosis and cirrhosis. Patients may develop decompensated liver disease manifested by ascites, splenomegaly, jaundice, esophageal varices, and hepatic encephalopathy.

Hepatocellular carcinoma is a dreaded complication of hemochromatosis with liver involvement. Patients with hemochromatosis are 20 to 200 times more at risk of developing HCC compared to the general population.

Diabetes Mellitus (Bronze Diabetes):

Another important and serious complication of iron overload is secondary Diabetes also called as bronze diabetes owing to the skin pigmentation associated with it.

Diabetes usually is present in patients who have already developed liver disease and skin changes.

Read the latest classification of Diabetes Mellitus

Heart involvement in hemochromatosis:

Patients can develop dilated cardiomyopathy that may manifest as heart failure and/ or conduction blocks.

Cardiomyopathy occurs as a result of iron deposition in the myocardium. Isolated heart involvement in the absence of other organs involvement is extremely rare.

The iron deposition may be seen by cardiac magnetic resonance imaging. Phlebotomy and iron chelation may improve ventricular dysfunction in these patients.

Hypogonadism resulting from an iron overload:

Iron deposition in the pituitary gland and gonads can result in hypogonadism. Secondary hypogonadism due to iron deposition in the pituitary gland is more common than primary hypogonadism.

Men may manifest with decreased libido, fatigue, lethargy, infertility, and biochemical evidence of low testosterone, LH, and FSH hormones.

Hypogonadism due to gonadal iron deposition may present similar to pituitary hypogonadism, however, LH and HSH may be raised.

Females, like men, can also develop central hypogonadism manifested by amenorrhea or ovarian failure.

Other pituitary hormonal levels should also be checked and may be affected depending on the degree of iron deposition.

Arthropathy (Joint involvement):

Patients may develop pseudogout due to the deposition of iron and calcium pyrophosphate in the joints.

Patients may be misdiagnosed as osteoarthritis since the clinical manifestations are almost the same except that arthropathy in hemochromatosis usually affects the young patients.

Other hemochromatosis symptoms may result from endocrinopathies that include hypothyroidism and hypoparathyroidism.

Patients are also prone to certain infections caused by iron loving organisms. These include:

  • Listeria causing meningitis and meningoencephalitis
  • Yersinia enterocolitica that involves the gut resulting in colitis
  • Vibrio vulnificus that causes septicemia and wound infections
  • Mucormycosis that may involve the sinuses, orbit, lungs, and the brain.

How to diagnose Hemochromatosis?

HH can be diagnosed by performing iron studies, imaging studies, Histopathological investigations, and the response to phlebotomy or chelation therapy.

Iron-studies – the cut-offs:

A fasting transferrin saturation of more than 60% in men and more than 50% in women can correctly identify more than 90% of the patients with hemochromatosis.

Serum ferritin of more than 300 ng/ml in men and 200 ng/ml may further supplement the diagnosis.

In patients with a strong clinical suspicion of hemochromatosis, the following cut-off values may be used as per the AASLD guidelines.

    • Transferrin saturation of 45%
    • Ferritin levels of more than 150 ng/ml in women and 200 ng/ml in men.

Liver Biopsy:

Liver biopsy is an invasive investigation and most experts now rely on genetic testing. The hepatic iron content of more than 71micromol of iron/gm of the dry weight of the liver is highly suggestive of homozygous HH.

The hepatic iron index (HII) is calculated as hepatic iron content divided by the person’s age. A value of more than 1.9 is consistent with the diagnosis, but not diagnostic.

CT, MRI, and SQUID techniques:

Radiological diagnosis via MR is increasingly being used especially in patients with heart involvement secondary to iron overload.

Magnetic susceptometry using a Superconducting Quantum Interference Device (SQUID) results of hepatic iron content is equivalent to those obtained by chemical analysis of liver biopsy tissue. However, because of the complexity, it is rarely used.

Genetic testing for hereditary hemochromatosis:

HFE gene mutation is now commonly advised where a hereditary cause of iron overload is suspected. HFE gene testing may be specially used as a screening test in the first degree relatives of patients with hereditary hemochromatosis.

HFE gene testing, when used for screening, may detect the disease in an early stage before the development of hemochromatosis symptoms, signs, and complications secondary to iron overload.

Patients with a positive test may be directed to abstain from pills and supplements containing iron and reduce the consumption of food sources rich in iron.

Read a case scenario of hemochromatosis with cardiomyopathy

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