| Who Gets Hemochromatosis? | | | | and maintain that level. Other comorbid conditions |
| Hereditary hemochromatosis (HH) is the most | | | | (conditions associated with HH) must be looked |
| common form of hemochromatosis. It is | | | | for and treated. Of especial importance is |
| predominately a disorder of persons of northern | | | | diabetes. The patients family should also be |
| European extraction. In this form of | | | | screened for HH. Those at greatest risk are the |
| hemochromatosis patients are most commonly | | | | patients siblings. However all first degree relatives |
| homozygous for (carry two copies of) the C282Y | | | | should be screened. Initial testing consists of |
| mutation of the HFE gene. Sometimes patients | | | | ferritin levels, transferrin saturations and genetic |
| may carry one copy of the C282Y mutation and | | | | testing. In this way many early cases of HH are |
| one copy of the H63D mutation. There are other | | | | now being picked up and successfully treated |
| forms of hemochromatosis and iron overload | | | | before patients load enough iron to give the |
| which will be discussed later. | | | | severe consequences of organ failure. |
| Hereditary hemochromatosis takes many years | | | | What Happens If The Patient Cannot Tolerate |
| to display its true nature. This is because it takes | | | | Venesections? |
| time to load iron in the body. Men usually load | | | | Our patient who we shall call Mrs. Abbott is a |
| more quickly than women. This is because | | | | small lady. She weighs in at just over 110 lbs and |
| women have monthly menstrual cycles and have | | | | is only 5 foot 2 inches tall. After Mrs. Abbotts first |
| children. Each pregnancy is equivalent to the loss | | | | venesection of 500 mls (which is equivalent to |
| of 1 gram of iron. So the bar is set lower to | | | | 250 mcg of iron) she is totally exhausted and has |
| confirm the diagnosis of HH in women. Before the | | | | difficulty standing for some three days. This is |
| true genetic nature of the disorder was | | | | despite adequate hydration before and after |
| recognized the diagnosis was made if the patient | | | | venesection. This lady is also known to have |
| could be venesected or deironed of 5 grams of | | | | osteoporosis (the rate of which is increased in HH) |
| blood (if male) without causing significant anemia. | | | | so it is important that she not fall as she could |
| If the patient was a woman only 3 grams of iron | | | | easily break an arm or worse a hip. Another |
| had to be removed by venesection without | | | | venesection is planned for a week later. |
| causing significant anemia to make the diagnosis. | | | | What needs to be done is to decrease the |
| Liver biopsy was not infrequently employed to | | | | standard venesection unit down to 250 mls and |
| confirm the diagnosis. | | | | probably do this every few weeks after she has |
| Now with the ready availability of genetic testing | | | | adequately recovered. It will take longer to deiron |
| the criteria are different. Often the diagnosis can | | | | Mrs. Abbott, but her treatment overall is safer. If |
| be made using genetic testing and iron studies. | | | | Mrs. Abbott had a ferritin level of say 2,000 ug/L |
| Liver biopsy is often now not necessary. | | | | then it would be a tougher call. She would need to |
| What Happens When A Patient Presents? | | | | be deironed more quickly. |
| Let us assume that a patient has presented with | | | | Immediately after venesection a cold pack was |
| fatigue and arthralgia (aching joints) to a doctor. | | | | applied to Mrs. Abbotts veins. This was done to |
| Now many things can give such a presentation. | | | | preserve the veins. This is especially important in |
| Paradoxically one of them is anemia or iron | | | | persons with frail veins and those who will need |
| deficiency. Anyhow let us assume that the patient | | | | multiple venesections. |
| is suspected of having hemochromatosis. The | | | | After a further 20 venesections of only 250 mls |
| patient is a lady of some 65 years of age. She | | | | each Mrs. Abbott has a ferritin level of 46 ug/L. |
| had five children and menopause at age 45 years. | | | | She has been successfully deironed. Her liver |
| She is of Irish/Scottish extraction and her mother | | | | function tests are now normal and her transferrin |
| died of liver problems yet her mother never | | | | saturation has fallen to 45%. Proper treatment is |
| drank a drop of alcohol in her life. The patient is | | | | to now monitor Mrs. Abbott and see how quickly |
| quite fair skinned. However this may be a red | | | | she loads iron. She is probably a patient who may |
| herring as not all patients with hemochromatosis | | | | only require 2 or 3 (half) venesections per year. |
| go a bronzed or grayish color. When the patient is | | | | Why Is It Important To Screen Relatives? |
| examined by the doctor she is noted to have | | | | Now Mrs. Abbott is from a very large family. She |
| enlarged and painful second and third knuckles and | | | | has 10 siblings, all of whom are younger and still |
| pain at the base of her thumbs. This is known as | | | | alive. There are 5 sisters and 5 brothers. All the |
| iron fist and is a clue to hemochromatosis. | | | | siblings are willing to be tested and live close. |
| Examination of the patients abdomen reveals an | | | | Often people simply do not want to know. This is |
| enlarged liver. So preliminary testing is done. This | | | | of course their right. |
| patient is found to have an enlarged liver on | | | | Because one C282Y mutation is inherited from |
| ultrasound but no cirrhosis. Her ferritin level is 650 | | | | each parent Mrs. Abbotts parents were at least |
| ug/L and she has a transferrin saturation of 96%. | | | | carriers of one C282Y mutation or were C282Y |
| In itself these are big clues this patient probably | | | | heterozygotes. Both her parents are deceased so |
| has HH. Genetic testing reveals the patient to be | | | | they cannot be tested. If we assume that both |
| a carrier of two copies of C282Y. Liver function | | | | parents were C282Y heterozygotes then the |
| tests are slightly abnormal. Now this patient has | | | | chance of each of their children carrying two |
| HH. A liver biopsy is probably not necessary as | | | | copies of C282Y is 1 in 4 or 25%. If one parent |
| the ferritin level is not markedly elevated. | | | | was a C282Y homozygote or carried two copies |
| Interestingly this patient almost certainly has | | | | of C282Y then the children have a 50% chance |
| fibrosis of the liver which may well be reversed if | | | | of carrying two copies of C282Y. If both Mrs. |
| the patient is properly deironed. | | | | Abbotts parents carried two copies of C282Y |
| The treatment for this patient is to deiron her | | | | then all her siblings will carry two copies of C282Y. |
| down to a ferritin level of 25 to 75 ug/L and try | | | | |