HemochromatosisHeredity Hemochromatosis Definition
Hereditary hemochromatosis is an inherited genetic disease in which there is excessive accumulation of iron in the body (excessive iron burden). He is a common genetic disorder among white people (Caucasians) in the United States, affecting approximately one in 240 to 300 Caucasians. Individuals suffering from hereditary hemochromatosis may have no symptoms or signs (and have a normal longevity), or they may have symptoms and signs of severe iron overload, including sexual dysfunction, heart failure , joint aches, liver cirrhosis, diabetes mellitus, fatigue, and darkening of the skin.
Normal iron content of the body is three to four grams. The total amount of iron in the body are carefully controlled. The body loses one mg of iron per day of sweat and cells that poured from the skin and inner lining of the intestines. The women also lost one mg of iron per day of menstruation. In normal adults the intestines absorb one mg of iron per day from food to replace the iron lost, and therefore, there is no excessive accumulation of iron in the body. When the iron losses is greater, more iron is absorbed from food.
In individuals with hereditary hemochromatosis, iron absorption from the intestines daily is greater than the amount needed to replace losses. Because the normal body can not increase spending on iron, absorbed iron accumulates in the body. In this iron accumulation figure, a person with hemochromatosis can accumulate 20 grams of total body iron at age 40 to 50 years. Excessive iron settles in the joints, liver, fruit-testicles, and heart, causing damage to these organs, and cause the signs and symptoms of hemochromatosis. Women with hemochromatosis accumulate iron at a speed more slowly than men because they remove more iron than men due to iron loss from menstruation and lactation. Therefore, they typically develop signs and symptoms of organ damage caused by iron overload 10 years later than men.
Hemochromatosis way Descendants Descended (inherited)
Hereditary hemochromatosis is an autosomal recessive disorder, meaning an individual's likelihood of developing iron overload mepunyai only if he inherits abnormal genes from both otangtuanya. (An autosomal recessive disorder is distinct from autosomal dominant disorder in which individuals can develop the disease by inheriting an abnormal chromosome from only one parents only).
The human body consists of trillions of cells. In the inner core (nucleus) of each cell are the chromosomes. Each human cell has two sets of 23 chromosomes (46 chromosomes total). Each set is derived from one parent. Chromosomes contain DNA that carry genes that regulate all body functions including cell metabolism, appearance, height, intelligence, hair color and eyes, and other physical characteristics. Damage to DNA (also called mutations) inherited from one generation to the next, and sometimes can cause diseases.
Mainly there are two mutations associated with hereditary hemochromatosis: C282Y and H63D. The numbers 282 and 63 points to the location of the damage to the erlokasi HFE gene on chromosome number 6. An individual who inherits two C282Y mutations (one from each parent) is called C282Y homozygotes, and he has a significant opportunity to develop hemochromatosis. In fact, C282Y homozygotes is responsible for 95% of cases of hereditary hemochromatosis. Patients who inherit a mutation from one parent and C282Y mutation H63D from the other parent the other so-called compound heterozygotes. They are responsible for three percent of cases of hereditary hemochromatosis.
Symptoms And Signs of Hemochromatosis
Patients with early hemochromatosis have no symptoms and are unaware of his condition. This disease may later revealed when blood levels of iron increased recorded by a routine blood test. In men, symptoms may not appear until 40-50 years old. Iron deposits in the skin causes the darkening of the skin. Because women lose iron through menstrual blood loss, they develop organ damage from iron accumulation 15 to 20 years later than men on average.
Deposits of iron in the pituitary gland and the fruits of shrinkage of the testicles causing fruits testicles and impotence. Iron deposits in the pancreas causes a reduction in insulin production resulting in diabetes mellitus. Iron deposits on the heart muscle can cause heart failure as well as abnormal heart rhythms (cardiac arrhythmias). The accumulation of iron in the liver causes liver scarring (cirrhosis) and an increased risk of developing liver cancer.
Diagnosing Hemochromatosis
Most patients with hemochromatosis is diagnosed early and have no symptoms. Hemochromatosis they found when levels of iron in the blood were found as part of routine blood tests, or when the levels of iron were measured as in studies of screening in family members with inherited hemochromatosis. Some patients were diagnosed to have hemochromatosis when their doctors do blood iron levels as part of the evaluation of abnormal elevations in blood levels of liver enzymes AST / SGOT and ALT / SGPT.
Iron Blood Tests
There are several blood tests that reflect the amount of iron in the body; levels of ferritin, iron levels, total iron binding capacity (TIBC) and transferrin saturation.
Ferritin is a protein-level blood levels correlate with the amount of iron stored in the body. Blood ferritin levels are usually low in patients with iron deficiency anemia, and is high in patients with hemochromatosis and other conditions that cause an increase in blood iron levels. Since ferritin can also be elevated in certain infections such as viral hepatitis and other inflammatory conditions in the body, an increase in ferritin levels alone are not sufficient to accurately diagnose hemochromatosis.
Serum iron, TIBC, and transferrin saturation are often implemented simultaneously. Serum iron is a measurement of the amount of iron in the serum (the liquid part of blood). TIBC is a measurement of the total amount of iron that can be carried in the serum by transferrin, a protein that carries iron in the serum from one part of the body to other body parts. Transferrin saturation (transferrin saturation) is a number calculated by dividing serum iron by TIBC - he is a figure that reflects how much percentage of transferrin that is being used to transport (carry) iron. In healthy individuals transferrin saturation is between 20 and 50 percent. In patients with iron deficiency anemia, serum iron and transferrin saturation is abnormally low, and in patients with hereditary hemochomatosis serum iron and transferrin saturation is abnormally high.
Because serum iron can be increased by eating and may fluctuate during the day, measurements of serum iron should be the time of fasting, usually the morning before breakfast.
Liver Biopsy
The most accurate test to diagnose hemochromatosis is a measurement of the iron content of liver tissue obtained by a biopsy. A liver biopsy involves the removal of a sample of liver tissue for analysis and is usually performed with a needle under local anesthesia. After making the skin and underlying tissues are numb, the doctor inserts a needle into the liver through the right rib cage, sometimes under ultrasound guidance. Tissue obtained by needle studied under a microscope for signs of active liver disease, fibrosis and cirrhosis (permanent scarring), and iron content (usually increase significantly in hemochromatosis).
Liver biopsy also has prognostic value because it determines whether the patient had suffered from advanced cirrhosis can not be changed. Patients with hemochromatosis but with a normal liver biopsy has a longevity that is similar to other healthy adults if treated adequately, in which patients with cirrhosis as a result of hemochromatosis have a longevity that is significantly reduced. Furthermore, the risk-risk patients with cirrhosis develop liver cancer (hepatocellular carcinoma) is much higher compared with normal subjects even with adequate treatment of iron overload by phlebotomy (see below).
Genetic Tests
The genes for hereditary hemochromatosis was identified in 1996. The genes are referred to as gene-gene HFE. Hereditary hemochromatosis is associated in most patients with two mutations of the HFE gene: C282Y and H63D.
A C282Y homozygote is someone who has inherited a gene that has mutated C282Y from each parent. A C282Y homozygote considered at risk of developing iron overload. In fact, C282Y homozygotes is responsible for 95% of all hereditary hemochromatosis. Conversely, not every C282Y homozygote develop iron overload. Studies have shown that an estimated 50% of C282Y homozygotes may not develop iron overload or its complications.
A compound heterozygote C282Y/H63D is someone who has inherited a gene that has mutated C282Y from one parent and a gene that has mutated H63D second from the other parent. Most compound heterozygotes had iron levels are normal although some can develop iron overload that mild to moderate.
A C282Y heterozygote is someone who has inherited a gene that has mutated C282Y from one parent but a normal second HFE gene from the other parent. Children who are born of two C282Y heterozygotes had a 25% chance to be a C282Y homozygote and, therefore, will be at risk to develop hemochromatosis. A C282Y heterozygote do not develop iron overload (iron overload).
A algoritmus to diagnose hereditary hemochromatosis are as follows:
1. Adults suspected of suffering from hereditary hemochromatosis (eg, adult, single-degree relatives of a patient with hereditary hemochromatosis) diperlakuan on measurements of fasting serum iron, TIBC, transferrin saturation and ferritin.
2. Pasein-patients with serum iron, ferritin, transferrin saturation increased and greater than 45% are treated on genetic tests.
3. Patients with transferrin saturation greater than 45% who have hemochromatosis are C282Y homozygotes and, therefore, should be treated with therapeutic phlebotomy (see below).
Who Should Undergo Liver Biopsy?
Not all patients with hemochromatosis need to run a liver biopsy. The purpose of liver biopsy is to identify patients with cirrhosis and to eliminate the possibility of other liver diseases. (Patients with hemochromatosis and cirrhosis are at risk of complications increased, especially liver cancer).
Young patients (less than age 40 years) who were C282Y homozygotes with liver blood levels are normal and serum ferritin levels of less than 1000 ng / ml have a very low risk of getting cirrhosis of the liver. Therefore, these patients can be treated by therapeutic phlebotomy without a liver biopsy. Their prognosis is very good with adequate treatment.
Patients who are older (older than age 40 years) who had serum ferritin levels greater than 1000 ng / ml, and had blood levels of abnormal rise in liver cirrhosis may have developed. Doctors may recommend liver biopsies in these patients with the condition that it is safe for them to undergo liver biopsy.
Caring for Hemochromatosis
The most effective treatment for hemochromatosis is to reduce iron in the body by phlebotomy (taking blood from the veins of the arm). One unit of blood, which contains 250 mg of iron, usually taken every one to two weeks. Serum ferritin and transferrin saturation are checked every two to three months. Once ferritin levels were below 50 ng / ml and transferrin saturations were below 50%, phlebotomy, phlebotomy frequency reduced to every two to three months. When hemochromatosis is diagnosed early and treated effectively, damage to the liver, heart, the fruit of the testicles, pancreas and joints can be prevented completely, and patients maintain normal health. In patients with cirrhosis who had been enforced, effective treatment can improve cardiac function, skin color, and diabetes; however, cirrhosis is irreversible and the risk of developing liver cancer remains.
The benefits of therapeutic phlebotomy in hemochromatosis are as follows:
* It prevents the development of liver cirrhosis and liver cancer if the disease is found and treated early.
* He is partially correct liver function in patients who have developed advanced cirrhosis.
* He is improving and / or fully eliminate the symptoms of weakness, pain / heart pain, joint pain, and fatigue.
* He is improving heart function in patients with mild heart disease and premature.
Recommendations Diet In Hemochromatosis
* A recommended keseimbagan normal diet without avoiding foods that contain iron on the condition of patients undergoing phlebotomy therapy is effective.
* Alcohol should be avoided as alcohol consumption increases the risk of developing cirrhosis and liver cancer.
* Consumption of high doses of vitamin C in patients with iron overload may lead to abnormal heart rhythms (cardiac arrhythmias) are fatal. Therefore, it is sensible to avoid supplements of vitamin C to patients are treated adequately.
* These foods raw seafood should be avoided because the patients with hemochromatosis are at risk of getting bacterial infections that thrive in environments that are rich in iron.
Recommendations Screening (Screening) For Liver Cancer In Hemochrmatosis
Cancer-liver cancer (hepatoma or hepatocellular cancer) mainly occurs in patients with cirrhosis. Therefore, patients with hemochromatosis and cirrhosis have to get abdominal ultrasound examinations and blood tests for alpha-fetal protein (a protein produced by liver cancer) every six months.
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