Group # 8 Balajadia, Abigael David, Rachel Rose De Vera, Sheryl Esguerra, Odessa Ginia Oate, Shimee Tomlyn

+

-thalassemia minor is a genetic disease that is not uncommon. It usually is asymptomatic and does not require treatment. This is a study of someone with this disease who is improperly treated. This is corrected by another physician and iron overload is prevented.

RG

13 YOWF of Greek descent who has been healthy all of her childhood. Exam:

Physical

Height :

52 Weight : 110 lbs Found to be in good health

TEST

RESULT

REFERENCE UNITSConventional SI

TEST

RESULT

REFERENCE UNITSConventional SI

Hgb

10 g/dl

10.3-14.9 103-149 g/dl g/L 32-42%

WBC

5.2 103 / l

5-103 / l

5-109 /L

Hct

30 %

% 18 % Lymph 82-98 fL RBC 5.3 x 106/

20-40% of total WBC

10004000/ mm3

MCV

57 m3

82-98 m3 26-34 pg/cell

4.0-5.2 x 4.0-5.2 x 106/mm3 1012/L 32-36 g/dl 320-360 g/L

MCH

19 pg/cell

0.40-0.53 MCHC 33 g/dl fmol/cell

When

the physician saw the lab values, she had her nurse contact RG and obtained additional information.

Nurse found out: RG has no complaints of being tired or short of

breath. RG established menarche ~ 1 yr ago, but until recently, it had been irregular. Lately, her periods were becoming more regular. Diet: RG did not consume much meat and did not take vitamins

Labs

indicating anemia were result of menses Since RG was just beginnig to go on a regular cycle and was losing more blood, and since she did not eat much meat or take vitamins and was ready to start a heavy exercise regimen Physician gave RG iron supplement Rx: Ferrous sulfate tablets 325mg OD, after

eating with glass of orange juice.

After several days of taking the iron. RG began to complain of having nausea in the

evening. This occurred everyday... Iron supplement? Pharmacist: Iron supplement could cause nausea RG was taking the iron with the evening meal RG stopped taking supplements for few days -> nausea went away She began taking it again, and it returned, so she stopped it altogether and called the doctor.

The physician that ordered the iron was out of town, RGs father decided to send her to her regular physician. He obtained a copy of labs and disagreed with tx. He ran some additional tests.

TEST

RESUL T 180 /dL ?

REFERENCE UNITSConventional SI

TEST

RESUL T 160 ng/ml ?

REFERENCE UNITSConventional SI

Serum Fe TIBC

50-120 /dL

9.0-21.5 Ferritin mol/L Transferrin Sat

7-140 ng/ml 15-50%

7-140 g/L

250-450 44.8g/dl 76.1 mol/L 203-360 2.0-3.6 mg/dl g/L

Transferrin

360 mg/dl

RBC morphology: leptocytisis, microcytic, hypochromic, with small numbers of target cells

Based on the new labs, RGs physician made a new Dx of + -Thalassemia minor, a genetic disease that directly affects nutrition in that it is concerned with iron metabolism. He D/Cs the iron tablets.

The growth chart shows curves representing percentiles that compare your child's weight and height with other children of the same age. Typically, a child who ranks in the 85th percentile or higher is either considered overweight or at significant risk of becoming overweight. At age 13: RG is 110 pounds, and that is at the 65th percentile for weight. Only 35% of the children same age weigh more than RG RG is 62 inches, and that is at the 50th percentile for height. 50% of the children same age are taller than RG

Low hgb Lower-than-normal hemoglobin may be due to:

Low MCV Anemias are defined based on cell size (MCV) and amount of Hgb (MCH). MCV less than lower limit of normal: microcytic anemia Macrocytic/normochromic anemia results from chemotherapy, folate deficiency, or vitamin B-12 deficiency. Low MCH MCH less than lower limit of normal: hypochromic anemia Microcytic/hypochromic anemia is caused by iron deficiency, lead poisoning, or thalassemia

Anemia (various types) Bleeding Destruction of red blood cells Leukemia Malnutrition Nutritional deficiencies of iron, folate, vitamin B12, vitamin B6 Overhydration

Low hct Low hematocrit may be due to:a

Anemia Bleeding Destruction of red blood cells Leukemia Malnutrition Nutritional deficiencies of iron, folate, vitamin B12, and vitamin B6 Overhydration

Iron forms an insoluble complex with several other drugs, resulting in decreased absorption of both iron and the other drug. Examples include tetracycline, penicillamine, methyldopa, levodopa, bisphosphonates and quinolones. The same can occur with elements in food, such as calcium. Absorption of iron is better at a low pH (an acid environment), and resorption is decreased if there is a simultaneous intake of antacids, phosphates, etc. Tannins from foods, such as tea and saw palmetto, reduce absorption of iron.

Side effects of therapy with iron are most often diarrhea or constipation and epigastric abdominal discomfort. Taken after a meal, side effects decrease but there is an increased risk of interaction with other substances. Side effects are dose-dependent, and the dose may be adjusted. The patient may notice that his/her stools become black. This is completely harmless, but patients must be warned about this to avoid unnecessary concern. When iron supplements are given in a liquid form, teeth may reversibly discolor (this can be avoided through the use of a straw). Intramuscular injection can be painful, and brown discoloration may be noticed.

Vitamin

C will enhance the absorption of iron many fold. However, for it to do so, it must be taken simultaneously with the iron. Both vitamin C and iron must be present together in the intestine for the positive effect to occur.

(a) Ferrous (II): Ferrous is "free" iron, generating destructive oxygen radicals; but its harmful effects are rare because most dietary iron is bound tightly in biological structures. l Ferrous fumarate is the anhydrous salt formed by combining ferrous iron with fumaric acid and used as a hematinic. l Ferrous gluconate is also used as a hematinic, but it is less irritating to the GI tract and used if ferrous sulfate cannot be tolerated. l Ferrous sulphate is the most widely used form to treat iron deficiency anemia, but it is an inorganic form and can destroy Vitamin E. l Organic iron compounds: ferrous gluconate, ferrous fumerate, ferrous citrate, or ferrous peptonate

(b) Ferric (III):l Ferric chloride, used topically as an astringent

and antiseptic lFerric fructose used as an iron-deficiency treatment. lFerric citrate is a highly available iron source that is converted to the ferrous state before absorption.

l l

l

l

Ferric iron is less readily absorbed than the ferrous form. Iron absorption occurs predominantly in the duodenum and upper jejunum Dietary Fe+3 (ferric) form is converted to the Fe+2 (ferrous) form in the stomach. The great advantage of this conversion is that the ferrous form (as compared to the ferric form) is much more easily released from the organic ligands to which it is bound and stays soluble. Ferric iron precipitates at pH >3 (as found in the duodenum) and is not available for absorption from such precipitates. Ferrous iron remains soluble up to pH values of about 7.5 and is available for absorption. (Duodenal pH increases from 4 to about 7) the ideal situation is either: Reduction of ferric iron (to ferrous iron) which can remain soluble at physiological pH in the duodenum, or: The formation of soluble chelates from which ferric iron can be readily released at the apical membrane of the duodenal enterocyte.

l

l

l

Iron enters the stomach from the esophagus. Iron is oxidized to the Fe3+state no matter its original form when taken in orally. Absorption of the enterocyte involves both a ferrireductase and a membrane transport protein (known as divalent metal transporter 1 or DMT1). The ferrireductase converts any free ferric iron into the ferrous form. The ferrous form is then transported across the membrane by DMT1. The gene for DMT1 contains an iron regulatory element and is consequently subject to control. Note that there are no transferrin receptors on this membrane and transferrin is not involved in this absorption. A feedback mechanism exists that enhances iron absorption in people who are iron deficient. In contrast, people with iron overload dampen iron absorption.

Factors That Influence Iron Absorption Physical State (bioavailability) heme > Fe2+ > Fe3+ Inhibitors phytates, tannins, soil clay, laundry starch, iron overload, antacids Competitors lead, cobalt, strontium, manganese, zinc Facilitators ascorbate, citrate, amino acids, iron deficiency

A number of dietary factors influence iron absorption. Ascorbate and citrate increase iron uptake in part by acting as weak chelators to help to solubilize the metal in the duodenum. Iron is readily transferred from these compounds into the mucosal lining cells. Conversely, iron absorption is inhibited by plant phytates and tannins. These compounds also chelate iron, but prevent its uptake by the absorption machinery. Phytates are prominent in wheat and some other cereals, while tannins are prevalent in (non-herbal) teas.

6. Distinguish between heme and non-heme iron in relation to where they are found, how they are absorbed, interfering factors, and the aids in absorption.

(a) Heme: Heme iron is present in the hemoglobin and myoglobin that is in blood Heme iron is found in animal foods that originally contained hemoglobin, such as red meats, fish, and poultry. That is why heme iron is found in red meat where it represents approximately 40 % of total iron. Excellent Sources of Iron Rich Foods Containing Heme Iron: Clams, Pork liver, Oysters, Chicken liver, mussels, beef liver (b) Nonheme: Most dietary iron is nonheme iron. Iron in plants such as lentils and beans is arranged in a different chemical structure called nonheme iron. Flours, cereals, and grain products that are enriched or fortified with iron are good dietary sources of nonheme iron. Excellent Sources of Iron Rich Foods Containing Non-Heme Iron: Enriched breakfast cereals, Cooked beans and lentils, Pumpkin seeds, Blackstrap Molasses

Dietary iron is absorbed in the proximal intestine by a regulated process that controls body iron homeostasis as iron excretion is not regulated in mammals. HEMEHeme iron is absorbed very efficiently by our bodies. Heme is taken into enterocytes by a carrier mechanism, and a folate transporter, PCFT (also called HCP1) Heme is degraded in enterocytes by heme oxygenase releasing iron ions for efflux via ferroportin.

NON-HEME Nonheme iron is not as well absorbed as heme iron. Non-heme food iron is release by acid digestion in the stomach and must be reduced to the ferrous (Fe2+) ion prior to uptake by duodenal enterocytes. Food factors, especially ascorbic acid, can reduce ferric (Fe3+) ions in the intestinal lumen, however an iron regulated ferric reductase protein (Dcytb, Cybrd1) is also present on the enterocyte apical membrane. Ferrous ions are transported across the enterocyte apical membrane by DMT1, a proton coupled divalent ion transporter. Iron effluxes from the enterocyte basolateral membrane through ferroportin and is oxidised by a membrane bound ferroxidase, hephaestin, yielding ferric ions that are then bound by plasma transferrin for distribution around the body via the blood. The absorption of Non-heme iron can be improved when a source of heme iron is consumed in the same meal.

Non-heme Iron Absorption Enhancers Vitamin C Beef Poultry Salmon

Non-heme Iron Absorption Inhibitors Coffee; Cocoa; tannic acid (in tea) Phytic acid (found in grains, legumes, and other plant foods) Egg protein (from both the white and the yolk) Minerals that compete with iron for absorption: calcium, zinc, magnesium, and copper Certain herbs, including peppermint and chamomile Fiber

Pork Citric acid

**Absorption of heme iron is very efficient and not significantly affected by the composition of diet.

Iron Absorption Enhancers Meat/fish/poultry Fruits: Orange, Orange Juice, cantaloupe, strawberries, grapefruit etc Vegetables: Broccoli, brussels sprouts, tomato, tomato juice, potato, green & red peppers White wine

Iron Absorption Inhibitors Red Wine, Coffee & Tea Vegetables: Spinach chard, beet greens, rhubarb and sweet potato Whole grains and bran Soy products

7. RG did not eat much meat. How does meat affect iron status?

Principle: The redder the meat, the higher the iron content. Iron is available in a wide variety of foods but is especially abundant in meat. The iron in meat protein can be efficiently absorbed, because heme iron in meat hemoglobin and myoglobin can be absorbed intact without first having to be dissociated into elemental iron. Iron in other foods, especially vegetables and grains, is often tightly bound to organic compounds and is much less available for absorption. Nonheme iron in foods and iron in inorganic salts and complexes must be reduced to ferrous iron (Fe2+) before it can be absorbed by intestinal mucosal cells.

Red

meat has a special effect on iron absorption. The iron in meat is more easily absorbed than iron in fruit, vegetables, cereals and eggs. Meat will also help the absorption of iron from vegetables and cereals when eaten at the same meal. Red meat, when eaten together with the vegetables, can boost the absorption of nonhemo iron by up to 400%.

Researchers in New Zealand have discovered that iron levels and bioavailability in meat are dependent on the degree to which meat is cooked and the type of cut. Iron needs to be in a soluble form in order to be absorbed into the blood, so the percentage of iron in the soluble-haem form was of particular interest, and this proved to be higher in beef than lamb by about 25 per cent. Much of the extra iron of beef relative to lamb appeared as the desirable soluble-haem iron. In a similar way those cuts with more iron tended to have a higher percentage as soluble haem iron.

Since RG did not eat much meat, she received too little iron in her body leading to low iron stores and iron deficiencies.

8. The physician saw something in the first set of lab values that caused him to look further for +-thalassemia minor. Hgb, hct were slightly down while MCV and MCH were down to a greater degree. These lab values with two other values triggered his suspicions. What other lab values would have done this and why?

The individual with thalassemia minor has only one copy of the beta thalassemia gene (together with one perfectly normal beta-chain gene). The person is said to be heterozygous for beta thalassemia.

COMPLETE BLOOD COUNT (CBC) It will give the doctor an evaluation of the size

and shape of the red blood cells present, also called the red cell indices. These include the mean corpuscular volume (MCV), a measurement of the size of the red blood cells. l A low MCV is often the first indication of thalassemia. If the MCV is low and irondeficiency has been ruled out, the person may be a thalassemia trait carrier.

BLOOD SMEAR (peripheral smear & manual differential). With thalassemia, the red blood cells are often microcytic (low MCV). Red cells may also: Be hypochromic Vary in size (anisocytosis) and shape (poikilocytosis) Be nucleated - normal, mature RBCs do not have a nucleus Have uneven hemoglobin distribution (producing target cells that look like a bulls-eye under the microscope). The greater the percentage of abnormal looking red blood cells the greater the likelihood of an underlying disorder and of impaired oxygen-carrying capability.

IRON STUDIES. These tests measure different aspects of the bodys iron storage and usage. They are ordered to help determine whether an iron deficiency is causing and/or exacerbating patients anemia. One or more of them may also be ordered to help monitor the degree of iron overload in a patient with thalassemia. These may include: Iron Ferritin Unsaturated iron binding capacity (UIBC) Total iron binding capacity (TIBC), and Percent saturation of transferrin.

HEMOGLOBINOPATHY (Hb) EVALUATION. This test measures the type and relative amounts of hemoglobin present in the red blood cells. Hemoglobin A, composed of both alpha and beta globin, is the normal type of hemoglobin found in adults. A greater percentage of Hb A2 and/or F is usually seen in beta thalassemia trait. Hb H may be seen in alpha thalassemia due to Hb H disease.

DNA ANALYSIS. This test is used to investigate deletions and mutations in the alpha and beta globin producing genes. Family studies can be done to evaluate carrier status and the types of mutations present in other family members. DNA testing is not routinely done but can be used to help diagnose thalassemia and to determine carrier status.

Iron Deficiency M V RDW RBC MI (MCV x RBC) Ferritin Ferritin Saturation Hemoglobin electrophoresis Response to Iron Therapy Other Lo High Lo > 13 Lo Lo Normal Lo

Beta-thalassemia Minor Low Normal Normal High < 13 Normal Normal Increased HbA2 (48%); Increased HbF (2-5%) No change Presence of basophilic stipling in peripheral blood film examination

Alpha-thalassemia Major Lo Normal High Normal High < 13 Normal Normal Normal

Iron Deficiency + Thalassemia Minor Lo High Normal Lo < 13 Lo Lo Lo Normal

Improves

No Change

Improves

LEPTOCYTOSIS: The presence of leptocytes in the circulating blood, as in thalassemia.x LEPTOCYTES: An abnormally thin erythrocyte. Such an erythrocyte is thinner than normal. It is commonly observed in iron deficiency anemia, thalassemias, chronic inflammatory disorders, and other conditions.

MICROCYTIC, HYPOCHROMIC ANEMIA: Characterized by abnormally small erythrocytes and reduced hemoglobin concentrations. This type of anemia results from deficiency of iron and impaired production of hemoglobin

Serum Fe measures the amount of circulating iron that is bound to

transferrin

TIBC Total iron-binding capacity measures the blood's capacity to bind iron with transferrin. To

assess the body's ability to transport iron in the blood.

Transferrin: A beta globulin in blood serum that combines with and

transports iron

Ferritin: Test to assess a person's iron stores in the body.

Transferrin saturation: Measures the amount of iron bound to transferrin in the blood. It is the ratio of serum iron and total iron-binding capacity,

multiplied by 100.

Formula: TIBC ( g/dL) = transferrin (mg/dL) x 1.25DATA: Lab result #2 Transferrin: 360mg/dl

TIBC ( g/dL) = 360 (mg/dl) x 1.25 = 450 g/dLREFERENCE UNITS: TIBC: 250-450 g/dL

Formula: Transferrin Sat% = Serum Fe ( g/dL) x 100% TIBC ( g/dL) = 180 g/dL x 100 450 g/dL = 0.4 x 100% = 40 %REFERENCE UNITS: Tranferrin Sat : 15-50%

characterized

by reduced synthesis of the hemoglobin subunit beta (hemoglobin beta chain) that results in microcytic hypochromic anemia, and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. disorder that reduces the production of hemoglobin. Hemoglobin is the iron-containing protein in red

blood

blood cells that carries oxygen to cells throughout the body.

Family

History

Thalassemias are inheritedthat is, they're

passed from parents to children through the genes. If your parents have missing or altered hemoglobin-making genes, you may have thalassemia. Ancestry

Beta thalassemias most often affect people of

Mediterranean (Greek, Italian, and Middle Eastern), Asian, or African origin or ancestry.

YES. RGs lab results suggest that she has anemia and yet, she is asymptomatic. She does not manifest signs of anemia. Also, the iron supplements given to her were no good which clearly suggests that the patients condition is THALASSEMIA.

Thalassemia minor has

only one copy of the beta thalassemia gene (together with one perfectly normal beta-chain gene) have (at most) mild anemia (with slight lowering of the hemoglobin level in the blood) heterozygous for beta thalassemia. No treatment is necessary

has

two genes for beta thalassemia and no normal beta-chain gene. homozygous for beta thalassemia Has a striking deficiency in beta chain production and in the production of hemoglobin A. Begins in the first months after birth.

Treatment includes: chronic

blood transfusion therapy iron chelation splenectomy allogeneic hematopoietic transplantation

Anemia is a decrease in the number of circulating red blood cells or in the overall hemoglobin concentration of the blood. Anemias can be classified according to red cell morphology and by pathophysiologic mechanism. TABLE

THALASSEMIA MINOR

IRON DEFICIENCY

Congenital, familial disorder of hemoglobin production Asymptomatic do not require any specific treatment

(acquired) Caused by loss of blood or faulty diet. symptoms include fatigue, loss of stamina, shortness of breath, weakness, dizziness, and pallor Oral supplemental iron

Iron supplementation will neither correct nor improve anemia due to thalassemia. Iron supplements IRON OVERLOAD

WHY?

Iron

overload is an excess (too much) iron in the body. Excess iron in vital organs, even in mild cases of iron overload, increases the risk for liver disease (cirrhosis, cancer), heart attack or heart failure, diabetes mellitus, osteoarthritis, osteoporosis, metabolic syndrome, hypothyroidism, hypogonadism, numerous symptoms and in some cases premature death.

RGs doctor suspected thalassemia because she has anemia and is a member of an ethnic group thats at increased risk for thalassemia. Her doctor also tested on the amount of iron in the blood to find out whether the anemia is due to iron deficiency or thalassemia. Iron deficiency anemia occurs when the body doesnt have enough iron to make hemoglobin. The anemia in thalassemia occurs because of a problem with either the alpha globin chain or the beta globin chain of hemoglobin, not because of a lack of iron.

Iron is a mineral supplement that can be found over the counter from almost any store where supplements are available. Iron overload, or overdose, occurs when too much is taken, whether it is accidentally or intentionally. Iron overload usually happens to children when they ingest vitamins, either pediatric or adult, that contain iron. Intestinal Effects Iron is a direct irritant to your stomach, as it corrodes the lining of your intestines. Symptoms usually develop within six hours after a large amount of iron has been swallowed and can include severe vomiting, diarrhea, abdominal pain and dehydration. If the poisoning has occurred in a child, there may be blood in the vomit or stool. After proper medical attention, symptoms begin to subside within 6 to 24 hours after onset. Nervous System Effects If iron overload is severe enough and sufficient treatment is not provided, this can result in shock or even death. Also, if enough iron is ingested, a coma may occur within 30 minutes to one hour after overdose. Severe iron toxicity in an individual is equated with a person ingesting more than 50 mg/kg of body weight. Other nervous system effects include dizziness, convulsions, chills, fever and headache. Skin Effects If you have ingested too much iron, you may experience some effects on your skin; you may lose color from your skin or become pale (also known as pallor), develop a bluish color on your lips and fingernails and you may even experience flushing. If you know that you have overdosed on iron, it is important to seek medical attention right away whether you are experiencing symptoms or not.

SubjectiveNausea in the evening due to iron supplement intake

ObjectiveMedication/s taken: Ferrous sulfate tablets 325mg once daily

First set of Lab results CBC TEST Hgb Hct MCV MCH WBC % lymph WBC RBC MCHC RESULT 10 g/dL 30% 57 mcg3 19 pg/cell 5.2 103 / mcL 18% 5.3x106 / u 33 g/dL 32-36 g/dL NORMAL 10.3-14.9 g/dL 32-42% 82-98 mcg3 26-34 pg/cell 5-103 / mcL 20-40% of total 4.0-5.2x106 mm3

Second set of Lab results CBC TEST Serum Fe TIBC Transferrin Ferritin ng/mL Transferrin saturation RESULT 180 mcg/dL 450 mcg/dL 360 mg/dL 160 ng/mL 40% NORMAL 50-120 mcg/dL 250-450 mcg/dL 203-360 mg/dL 7-140 15-50%

Assessment

Patient RG was first suspected with anemia. Her first set of lab results showed that she was anemic but as she continue to take iron supplements, nausea results. RGs parents decided to ask for a second opinion to her regular physician who disagreed with the therapy given to her. The physician ruled out Beta thalassemia minor, which was proven by the second lab results. When RG was asked about her diet, it was found out that she didnt consume much meat and didnt take vitamins.

Plan

As for diet, avoid foods that contain iron. Some thalassemia patients must get regular blood transfusions. This causes an excess build up of iron in the body which can damage the heart and other organs. Proteins that are high in iron and should be avoided include liver, oysters, pork, beans, beef, peanut butter and tofu. Grains that are iron rich include flour tortillas, infant cereal, and cream of wheat. Fruits and vegetables that contain iron and should be avoided include prunes, watermelon, peas, broccoli, raisins, spinach, and leafy green vegetables. Eat plenty of foods that contain calcium. This is extremely important for keeping the bones strong and healthy. This is crucial for people who have thalassemia since frail and brittle bones can be a complication of the disease. Dairy products are a good source of calcium. An added benefit is that dairy products reduce the body's ability to absorb iron.

Include vitamin D in your diet. Vitamin D is needed so that the body can absorb calcium. Vitamin D is contained in eggs, dairy products and fish. It is of utmost importance for thassalemia patients to increase the intake of folic acid in the form of supplements or natural diet. A type Vitamin b-9, is necessary for cell replication and its growth. Folic acid is present in foods such as beans, beetroots, milk, leafy vegetables like spinach, fruits (oranges and bananas), whole wheat bread, meat and others. Depending upon the treatment and other factors, one must increase iron intake and Vitamin B considerably. Ideally, meat is the best diet for thalassemia patients. It can be red meat, lamb, beef, chicken, liver and pork. In spite of red meat, you could opt for soy proteins. If you like chicken, go in for white part of the chicken, which contains more iron. Besides meat products, it is essentially necessary to balance your diet with variety of dairy products, fruits, underground and leafy vegetables, eggs and cereals. In order, to make iron absorbable faster in the body, make sure that your diet includes a lot of milk or dairy products. Try to drink a glass of milk with your meals or use it while cooking your curries or snacks

Nutritional genomics, or nutrigenomics, is the study of how foods affect our genes and how individual genetic differences can affect the way we respond to nutrients (and other naturally occurring compounds) in the foods we eat. Nutrigenomics has received much attention recently because of its potential for preventing, mitigating, or treating chronic disease, and certain cancers, through small but highly informative dietary changes.