Hemochromatosis: Introduction

Introduction

Figure 1. Location of the liver in the body.

Hemochromatosis was first identified in the 1800s, and by 1935 it was understood to be an inherited disease resulting in iron overload and deposition. Today, hemochromatosis is defined as a metabolic disorder affecting iron absorption, and resulting in the accumulation of excess iron in the body’s organs.

Hereditary hemochromatosis (HH) is an autosomal recessive disorder that affects one in three hundred people in the United States. One in nine people carry the gene—making hemochromatosis the most common genetic disorder in the United States. It is primarily seen in middle-aged men of Northern European descent, and postmenopausal women. Treatment is readily available and the prognosis, with early diagnosis and proactive treatment, is a normal life expectancy. If untreated, hemochromatosis may lead to cirrhosis.

Make an appointment today - call (410) 955-4166

General Info

What is Hemochromatosis?
Despite being the most prevalent monoallelic genetic disease in Caucasians, hereditary hemochromatosis is under-diagnosed. There are several reasons for this, including lack of awareness, a long latency period, and nonspecific symptoms.

Figure 2. Deposition of iron in the liver; A, Gross liver; B, Histological view.

Normal iron absorption occurs in the proximal small intestine at a rate of 1-2 mg per day. In people with hereditary hemochromatosis, this absorption rate can reach 4–5 mg per day with progressive accumulation to 15–40 grams of iron in the body (Figure 2). Humans have no physiologic pathway to excrete iron. Therefore, iron can accumulate in any body tissue, although depositions are most common in the liver, thyroid, heart, pancreas, gonads, hypothalamus and joints. Hemochromatosis causes or exacerbates arthritis, diabetes, impotence, heart failure, cirrhosis of the liver and liver cancer.

The liver is the organ most affected by hemochromatosis, because of its relatively large blood flow. Blood from the portal circulation (which comes from the intestines) goes straight to the liver. Once the body absorbs iron, it is not lost until blood is lost. Extra iron in the body causes an overproduction of free radicals and this results in injury that may affect any organ.

Hereditary hemochromatosis is an autosomal recessive inherited disorder that occurs in approximately 1 in 300 people, ultimately making them more susceptible to cirrhosis and liver failure. People who inherit two abnormal genes will most likely develop hemochromatosis even with a normal diet, whereas those with a single gene may absorb more iron than the average person without developing full-blown disease.

Hereditary hemochromatosis is distinct from secondary iron overload, which also causes increased iron absorption and increased iron deposition. Cases of secondary iron overload include ineffective erythropoiesis (where erythroid cells are destroyed near the site of their development within the bone marrow) such as thalassemia syndromes, congenital dyserythropoietic anemias and sideroblastic anemias, other forms of liver disease, and congenital atransferrinemia. An acquired form of this condition may result from too much intravenous iron or too many blood transfusions.

Symptoms
The clinical manifestations of hemochromatosis usually appear after significant iron accumulation—generally after the age of 40. Symptoms appear earlier in males than in females due to the loss of iron through menstruation in women.

Many patients with hemochromatosis are asymptomatic and are diagnosed only as a result of family screening, or after blood tests suggest increased iron. Early signs are nonspecific and can include weakness, lethargy, increased skin pigmentation, hair loss, impotence, joint pains, vertigo, and loss of memory. Iron deposition in heart muscle may cause arrhythmias or degeneration of the muscle itself (resulting in cardiomyopathy). Patients with hemochromatosis are also at increased risk for diabetes and pancreatic cancer. Iron deposition in the liver leads to enlargement and elevation in liver enzymes (Figure 3). This may cause right upper quadrant pain and predispose patients to fibrosis, cirrhosis and cancer. Hepatocellular carcinoma develops in 30% of patients with cirrhosis due to hemochromatosis, and the incidence of hepatocellular carcinoma increases with age, reaching almost 50% in patients over 60 years of age.

Figure 3. Symptoms and signs of hemochromatosis.

Most of the outward manifestations of hemochromatosis are the result of iron deposition in the organs. Exceptions include the bronze color of a patient’s skin—which is due to increased melanin deposition—and arthritis, which is due to calcium pyrophosphate crystal accumulation (pseudogout). Arthritis develops in 25–30% of patients and initially involves the second and third metacarpophalangeal joints (Figure 4). Thereafter, a progressive polyarthritis involving the wrists, hips, knees, and spine may ensue. Hypogonadism is the result of decreases in follicle stimulating hormone and luteinizing hormone secretion (from iron deposition in the anterior pituitary gland) and is manifested through impotence in males and amenorrhea in females. Primary testicular failure and atrophy may also occur from iron deposition in the testes.

Figure 4. Arthritis of the hand.

Make an appointment today - call (410) 955-4166.