Diagnose-Me: Condition: Hemochromatosis (Iron overload)

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	Hemochromatosis (Iron overload)

Hemochromatosis
Signs, symptoms, indicators
Conditions that suggest it
Contributing risk factors
Treatment recommendations

Hereditary Hemochromatosis (HHC) is characterized by increased iron absorption in the gastrointestinal tract that may cause lifelong excessive iron absorption and accumulation and serious health effects including arthritis, cirrhosis, diabetes, impotence, myocardial infarction, and death. Incidence; Causes & Development

HHC is one of the most common genetic disorders in the United States, affecting approximately 1.5 million persons.

HHC is commonly underdiagnosed in white patients. In other ethnic groups, such as African Americans and Hispanics, it may not even be considered despite the presentation of signs and symptoms strongly suggestive of iron overload. The prevalence of iron overload among Hispanic persons is estimated to be as high as 5 in 1,000 persons.

HHC, an autosomal recessive disorder previously considered to be rare, is now known to be the most prevalent genetic disease in individuals of northern European descent. The hemochromatosis gene is responsible for most cases of HHC. The prevalence of the homozygous genotype is estimated to be 1 in 250 persons; the prevalence of the heterozygous genotype is approximately 1 in 8 persons.

Evidence suggests that primary iron overload may be common in African Americans. Hepatic iron excess was observed in 1.5% of African Americans during a recent autopsy series and in 10.4% of African Americans who underwent liver biopsy during medical care delivery. In a large nutrition survey among the general African American population aged 3 to 45 years, hyperferritinemia consistent with iron overload was more common among African Americans than whites.

HHC was first recognized more than a century ago as an iron overload condition presenting as a clinical triad - type 2 diabetes mellitus, skin bronzing, and cirrhosis of the liver. Several causes for iron overload exist, the primary ones being genetically based. Secondary iron overload may be the result of excessive transfusion therapy, poorly responding anemia being treated with iron supplementation, or chronic liver disease due to alcohol abuse.

Persons with normal hemoglobin levels and iron stores absorb just enough iron to meet their daily needs and balance losses (1mg per day). No internal mechanism exists for excreting excess iron absorbed from the diet. The amount of iron absorbed is influenced by the amount of iron stored in the body, the rate and effectiveness of red blood cell creation, the amount and form of iron in the diet, and the presence of iron absorption enhancers and inhibitors in the diet. However, patients with HHC continue to absorb high amounts of dietary iron even when their bodies have enough or too much iron.

HHC patients can chronically absorb a small excess of iron each day, resulting in iron stores 10 times the normal amount by the time they are middle-aged. The body is unable to adequately chelate and store this amount of iron. Therefore, unbound iron accumulates and generates free radicals, leading to cellular injury of the liver and other organs.

Signs & Symptoms

The first symptoms associated with iron overload are often nonspecific and the disorder may not be considered in the differential diagnosis. Consequently, the underlying cause may not be recognized and treated and organ damage may continue. At least 50% of men and 25% of women with both genes for HHC are likely to develop potentially life-threatening disease complications, especially in countries where there is high dietary intake of iron.

The clinical manifestations of HHC usually do not appear until a person is aged 40 to 60 years, when sufficient iron has accumulated to cause organ damage. Some persons have clinical manifestations by 20 years of age, but others with both genes for the disease may never have clinical signs. Depending on which study one reads, an estimated 67% to 94% of men and 41% of women with HHC show signs and symptoms of the disease after 40 years of age.

Diagnosis & Tests

The use of supplementary iron and vitamin C (which increases iron absorption) may lead to earlier laboratory abnormalities and iron deposition. Conversely, blood donation, physiologic blood loss (through menstruation and pregnancy), and pathologic blood loss (for example, through peptic ulceration or inflammatory bowel disease) may decrease the amount of iron stored in the liver. However, the belief that premenopausal women cannot develop symptomatic or even life-threatening HHC is a misconception.

Liver biopsy continues to be the gold standard for diagnosis and staging of HHC because it can detect the level of iron overload and identify hepatic fibrosis and cirrhosis. Many specialists prefer liver biopsy to quantitative phlebotomy, particularly when clinical or laboratory evidence of hepatic involvement is present. In patients younger than 40 years who have an serum ferritin concentration of less than 750 ng/mL and normal liver enzyme levels, phlebotomy therapy can be started without a liver biopsy. In all other cases, biopsy remains essential for diagnosis and optimal management.

Once a diagnosis of HHC is confirmed, the patient should have the excess iron removed and family members should be screened for the disorder. Iron overload is treated with successive phlebotomies in patients with or without clinical manifestations. The total amount of blood that must be removed to produce iron deficiency provides an estimate of total body iron load.

Diagnosis of HHC is commonly delayed until clinical manifestations have appeared and irreparable organ damage has occurred. Therefore, basic and continuing medical education about the disease is urgently needed. Simple screening tests, such as serum transferrin saturation and ferritin concentrations, can be helpful in discovering asymptomatic patients with iron overload.

Performing iron studies on routine screening chemistry panels has become more commonplace as demonstrated by a study of 40 patients with newly diagnosed HHC prospectively referred to a tertiary university-based hepatology clinic. Clinical information, serum and liver iron studies, liver histology, and phlebotomy requirements were evaluated to see what features were most helpful in making the diagnosis.

The study documented that 83% of patients came to the attention of the medical staff as a result of routine blood screening. Of these patients, 73% were asymptomatic and 78% had normal physical examinations. Only 3 patients had cirrhosis from HHC alone, 2 patients were diabetic, and 2 patients had increased skin pigmentation. With the use of iron screening studies on routine serum chemistry panels, patients with HHC can be identified and subsequently treated before symptoms or organ damage occurs.

Prognosis; Complications

The causes of death in untreated patients include cardiac failure (30%), liver failure or portal hypertension (25%), and hepatocellular carcinoma (30%). The degree of iron overload at the time of diagnosis, as well as organ dysfunction, have prognostic implications. The 5-year survival rate increases with treatment from 33% to 89%. However, discovering HHC prior to the onset of tissue or organ damage is very important. When HHC is found early and properly managed, long-term prognosis, including life expectancy, should not differ from that of persons without the disorder.

Deposition of iron within tissues causes inflammation and subsequent fibrosis and destruction of major organs leading to organ failure and chronic disease. HHC often goes undetected and untreated until symptoms of permanent organ damage become apparent.

Type 2 diabetes mellitus develops in about 65% of patients and is more commonly a complication in patients with a positive family history for diabetes. Hypogonadism is common in both sexes and can lead to loss of libido, impotence, amenorrhea, testicular atrophy, and loss of body hair.

Arthropathy is present in up to 50% of symptomatic patients. Occasionally, acute episodes of an inflammatory arthritis occur; some of these episodes are caused by deposits of calcium.