A: Hemochromatosis (pronounced: He-mo-chro-ma-toe-sis) is a genetic condition of abnormal iron metabolism that permits absorption of too much iron from an ordinary diet. Hereditary hemochromatosis is an autosomal recessive disorder. It is NOT a blood disease. It is also known as iron overload or iron storage disease. It is possible for someone who has never had an iron pill in his/her life to have iron overload.

A: Yes, iron overload can be acquired. The genetic form is known as primary hemochromatosis, hereditary hemochromatosis (HH) or (HHC), or genetic hemochromatosis (GH) and idiopathic hemochromatosis (from an unknown origin), term which is rarely used anymore. The acquired form (through massive doses of iron pills or blood transfusions) is known as secondary hemochromatosis, acquired hemochromatosis, or transfusional iron overload.

A: Frequency (incidence in the general population) of the abnormal gene is: 1 in 100-200 people has hemochromatosis (double gene mutation known as a homozygote) and 1 in 8-10 people is a carrier of hemochromatosis (single gene mutation known as a heterozygote or "het" for short). That's approximately 32 million Americans who are carriers and 1.5 million Americans have the double gene which can lead to full blown hemochromatosis. Recent studies in Ireland, show a frequency of 1 in 4 as carriers of the single mutation and 1 in 64 as double gene mutation. Because of this high frequency, routine screening for hereditary hemochromatosis is medically indicated.

A: Most affected people DO NOT KNOW they are accumulating dangerous stores of iron. Tragically underdiagnosed, no race, age, or gender is immune. (Premenopausal women do have iron overload as well as young children) The American Hemochromatosis Society (AHS) has made an official position statement and issued guidelines for diagnosis, treatment, and management of iron overload/hereditary hemochromatosis, including recommendations that all Americans age 2 years and older be routinely and universally screened for iron overload as well as genetic screening. All ethnic groups can be affected, but those with an Irish/Scottish/Celtic/British heritage have an even higher prevalence of the HH mutation. Hispanics and Afro Americans also have iron overload.

A: The excess iron injures body organs and KILLS unless detected in time for adequate iron storage removal. It is a very serious disease, but quite benign if detected early before organ damage has occurred. That is why routine screening is so important. HH is a lethal but treatable disease. Don't let anyone tell you that iron overload/HH is "nothing to worry about".

A: Yes. Hereditary hemochromatosis is one of the few genetic diseases which has a prevention plan so that all organ damage and premature death can be completely prevented. When the excess iron IS detected EARLY and is ADEQUATELY removed, the individual can enjoy a normal life span in normal health.

A: Patients can have iron overload and NOT have symptoms (asymptomatic) and that is the best time to diagnose the patient. Many doctors have been taught to look for "signs and symptoms" of HH but by the time symptoms appear, it is often too late to save the patient's life. Iron overload and storage in vital body organs can damage and may cause:

• chronic fatigue (the most common complaint by patients);
• cirrhosis/cancer of the liver (with or without a history of alcohol use);
• arthritis/joint pain;
• impotence/sterility/infertility; early menopause/irregular menses;
• hair loss;
• diabetes (bronze diabetes, a darkening, graying of the skin not caused by sun exposure);
• cancer (cancer thrives on iron);
• abdominal pain/swelling;
• weight loss;
• frequent colds/flu/infections, compromised immune system;
• headaches;
• hypothyroidism;
• heart irregularities/heart failure/heart attack (especially in younger men);
• cirrhosis of the liver (with or without a history of alcohol use);
• hepatoma/liver cancer (the leading cause of death in HH);
• premature death.

Anyone with any combination of these symptoms, or a family history of these symptoms, should be tested for HH immediately. But remember, two important facts: 1.) There can be numerous generations of "silent carriers" of the mutation who never become ill and live to old age thereby giving a "false security" that HH doesn't "run in the family" 2.) Some patients do not have symptoms until they are end stage and their lives cannot be saved. Early detection should be achieved through: 1.) Knowledge of genetic risk through DNA Testing 2.) Annual screening with serum iron, TIBC, and serum ferritin to assure that iron storage is not taking place.

A: Blood banks do NOT screen for iron overload/hemochromatosis. They are basing their comments on the hematocrit or hemoglobin readings that they take prior to a blood donation (the finger prick test) and these are not the correct tests for iron overload storage! Yet blood banks continue to give out false information to their clients, telling them that they have low "iron" or even in some cases that their iron is high! The iron-overloaded person may be anemic at the same time. There are several types of anemia that are iron-loading! Hematocrit and hemoglobin are NOT tests for iron overload/hemochromatosis; ask your physician to test you with transferrin saturation (TS) which is calculated by dividing the serum iron by the TIBC (total iron binding capacity) and serum ferritin to confirm or rule out iron overload.

A: A simple series of blood tests which can be performed by any doctor or lab can indicate iron levels. They must be proper iron measures: Total Iron Binding Capacity (TIBC) together with Serum Iron. Divide TIBC into Serum Iron to get the percentage of transferrin saturation. It is important that the serum ferritin is also performed at the same time and it should be done, if possible, while fasting. Refrain from iron pills for a week prior to the tests. A new test, serum ferritin-iron assay will also be available in the near future. The discovery of the hemochromatosis gene was announced in August 1996 by Mercator Genetics Inc. of Menlo Park, California (which was purchased by Progenitor in 1997. Recently, Bio-Rad Laboratories of Hercules, CA bought the patent from Progenitor. Bio-Rad currently holds the patent to the HFE mutation). The new genetic DNA test (HLA-H now known as HFE or HFe) has been commercially commercially available from many labs around the nation since 2/1997, including SmithKline Beecham Clinical Laboratories currently known as (Quest Diagnostics) on a nationwide basis. Many university labs and other smaller independent genetics labs across the nation now offer the DNA testing for HH, but many of them only test for the one mutation (845A also known as Cys282tyr) so you want to make sure the lab you use tests for BOTH HH mutations (845A and 187G). Two labs which test for both mutations and which offer a handy "cheek brush" tissue collection kit which you can get through the mail and perform in the privacy of your own home: Kimball Genetics in Denver, Colorado (1-800-320-1807 or 303-320-1807 in Denver or outside of the U.S.A.) and Michigan State University (MSU) ( 517) 353-2032. The "cheek brush" method (no needles/blood/pain) is great for kids and adults. More info on how to order these tests is available from the AHS office at 407-829-4488.

A: First of all, always get copies of your medical lab reports for your home medical file and review them yourself. Make sure that the serum iron, TIBC, and serum ferritin tests are on the report and double check to make sure that you fall into the "safe zone" set by AHS--a ferritin under 150 and a saturation percentage of under 40%. Some labs have very "high" normal levels and you might not really be in a safe zone. Many patients have contacted us who have iron studies in the "danger zone" but their doctors have told them that they are fine. It is prudent to find out for yourself. The same philosophy applies to the DNA test--make sure you get copies of the report for your own files and know if you have the single or double mutation and which of the two mutations you carry (you can even carry one of each known as a compound heterozygote).

A: LOW iron means investigate the cause: cancer? internal bleeding? chronic infection? It is dangerous to take iron without knowing the reason for the iron deficiency. Your doctor should thoroughly investigate the cause of your low iron before prescribing iron pills. Victor Herbert, MD JD, Professor of Medicine at Mt. Sinai School of Medicine in New York City states that no one should take iron supplements without first assessing their iron storage status.

A: Yes. Even if your first test was negative, ideally, you should be monitored annually by your physician. Also, by having the DNA test, you can discover if you have the single or double gene for hemochromatosis and determine your risk factor of developing full blown hemochromatosis or passing a mutation to offspring. A very small percentage (about 12% to 15%) of patients who are clinically iron overloaded (have high TS and serum ferritin levels) may have a negative result on the genetic test. Scientists believe that these persons have still another HH mutation (which has yet to be discovered and a test for it developed) which is causing this iron storage. For this reason, it is always wise to test using the transferrin saturation and serum ferritin annually to be on the safe side.

A: A percent of saturation of more than 40% and/or a serum ferritin of more than 150 are considered suspicious for iron overload/hemochromatosis. It is important to note that in some patients, the percent of saturation can be quite high while the ferritin rather low (this is often the case in children or young adults in their 20's) or conversely, with normal percent of saturation and a high serum ferritin. Genetic testing can, in most cases, confirm the diagnosis so that treatment can begin. Ask your doctor about liver function tests, if these are also elevated, that is another possible sign of HH.

A: Confirmation of a diagnosis is based on a combination of several factors; these will vary from doctor to doctor on which ones are used: a.) Elevation of iron tests such as transferrin saturation and serum ferritin b.) Elevation of liver enzymes (abnormal liver function tests) c.) Symptoms (diabetes/heart disease/arthritis/impotence/infertility/bronzed skin, liver disease) d.) Liver biopsy showing hepatic iron index (HII) and such liver diseases as cirrhosis/cancer e.) DNA genetic test (results are available between 1 to 14 days depending on the lab used) f.) CT/MRI/Ultrasound of the liver showing deposition of iron in the liver or hepatoma(s) (liver tumors). g.) Quantitative phlebotomy (a trial series of six weekly phelobotomies to confirm diagnosis; if the hematocrit remains 35% or greater immediately prior to each phlebotomy. Six weeks of weekly bloodletting is another way to confirm iron overload, hemochromatosis) h.) Alpha Fetoprotein bloodwork ruling out liver cancer due to HH. i.) EKG to rule out heart damage from HH. j.) Family history of iron overload, especially parents/siblings, who should also be screened with transferrin saturation and serum iron and genetic tests for comparison. If no family history of diagnosed hemochromatosis, check family medical history for symptoms of undiagnosed HH, such as heart disease, early heart attacks especially in men (in their 30's), liver cirrhosis/cancer, diabetes, arthritis, impotence, infertility, chronic fatigue syndrome, etc.

A: A CT or MRI of the abdomen will only tell you that the liver is very "dense" due to iron content. They do not give you any details such as if there is cirrhosis or not or if there is scar tissue, etc. The density can be measured and it has a very good correlation with the amount of iron in the liver. Both CT and MRI are very good to detect hepatomas (cancerous tumors of the liver) very early and very well. They also help to tell us if they can be surgically removed or not. Ultrasound is another technique that can be used as well and is less expensive than the CT or MRI and uses no radiation like the CT. In fact, an ultrasound with an ACUSON would be advisable in order to maximize any chances of finding an early lesion that might be confined to one lobe and therefore potentially resectable (operable).

A: A liver biopsy has been used as the "gold standard" by many physicians for decades to confirm a diagnosis of hemochromatosis. It will show your "hepatic iron index" (HII) or how much actual iron is in your liver tissue, a popular storage site for iron in the hemochromatosis patient. In the past, a patient was determined to be a "carrier" or a double gene mutation patient based on how much iron was in their liver. This was, of course, "educated guessing" because a liver biopsy is NOT a genetic DNA test and cannot in any way tell you if you have either of the mutations now known to affect iron metabolism in HH patients. With the advent of the DNA genetic test, doctors are now able to definitively determine a patient's genetic status with or without the liver biopsy, making using the liver biopsy as a means of diagnosis rather obsolete in most cases. The liver biopsy is an invasive procedure and does have morbidity and mortality (injury and death) in a small percentage of procedures. The chance of internal bleeding during or after this procedure has, in some cases, resulted in death of the patient. The advantage of the liver biopsy is that it alone can determine if a patient has cirrhosis of the liver and/or other liver diseases and to what extent. The determination of liver cirrhosis helps the doctor to make a more accurate prognosis for the patient since liver cirrhosis may (not always, but may) lead to liver cancer (hepatoma) at a later date. This prognosis, however, does not alter the treatment plan for HH. Patients with liver cirrhosis can be followed carefully to watch for any medical problems and annually tested with the alpha fetoprotein blood testing to detect early cancer of the liver when it might be surgically removed. The liver biopsy alone is not a good test to detect liver cancer as the sample may be benign but another section of the liver may have a tumor, hence the importance of having an ultrasound, CT, or MRI of the liver to rule out hepatoma in all HH patients. The liver biopsy should be discussed in detail with the physician before deciding to have this procedure done. Also, in the cases of early diagnosis (lower iron levels, no elevated liver enzymes, patient is asymptomatic (no symptoms), young or a child, many physicians now feel that the liver biopsy is not necessary