1|PageMENDELIAN DISORDERS : INTRODUCTION Mendelian disorder is a category of Genetic disorder. They are mainly determined by alteration or mutation in the single gene .These disorders are transmitted to the offspring on the same lines as in the principle of inheritance.The pattern of inheritance of such mendelian disorders can be traced in a family by pedigree analysis.most common and prevalent mendelian disorders are Haemophilia, Cystic Fibrosis, Sickle-cell anemia, and Thalassemia. Such mendelian disorders may be dominant or recessive. By pedigree analysis one can esily understand whwther the trait is dominant or recessive. Similarly the trait may also be linked to the sex chromosome as in case of Haemophilia. It is evident that this X-linked recessive trait shows transmission from carrier female to male progeny. SICKLE CELL ANEMIA What Is Sickle Cell Anemia? Sickle cell anemia is the most common form of sickle cell disease (SCD). SCD is a serious disorder in which the body makes sickle-shaped red blood cells. “Sickle- shaped” means that the red blood cells are shaped like a crescent. Normal red blood cells are disc-shaped and look like doughnuts without holes in the center. They move easily through your blood vessels. Red blood cells contain an iron-rich protein called hemoglobin. This protein carries oxygen from the lungs to the rest of the body.Sickle cells contain abnormal hemoglobin called sickle hemoglobin or hemoglobin S. Sickle hemoglobin causes the cells to develop a sickle, or crescent, shape. Sickle cells are stiff and sticky. They tend to block blood flow in the blood vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage. It can also raise the risk for infection. 2|Page Normal Red Blood Cells and Sickle Cells Figure A shows normal red blood cells flowing freely in a blood vessel. The inset image shows a cross-section of a normal red blood cell with normal hemoglobin. Figure B shows abnormal, sickled red blood cells blocking blood flow in a blood vessel. The inset image shows a cross-section of a sickle cell with abnormal (sickle) hemoglobin forming abnormal strands. Overview Sickle cell anemia is one type of anemia. Anemia is a condition in which your blood has a lower than normal number of red blood cells. This condition also can occur if your red blood cells don't contain enough hemoglobin. Red blood cells are made in the spongy marrow inside the larger bones of the body. Bone marrow is always making new red blood cells to replace old ones. Normal red blood cells live about 120 days in the bloodstream and then die. They carry oxygen and remove carbon dioxide (a waste product) from your body. 3|Page In sickle cell anemia, the abnormal sickle cells usually die after only about 10 to 20 days. The bone marrow can't make new red blood cells fast enough to replace the dying ones. Sickle cell anemia is an inherited, lifelong disease. People who have the disease are born with it. They inherit two genes for sickle hemoglobin—one from each parent. People who inherit a sickle hemoglobin gene from one parent and a normal gene from the other parent have a condition called sickle cell trait. Sickle cell trait is different than sickle cell anemia. People who have sickle cell trait don't have the disease. Like people who have sickle cell anemia, people who have sickle cell trait can pass the sickle hemoglobin gene to their children. SICKLE CELL MUTATION Outlook Sickle cell anemia has no widely available cure. However, treatments to improve the anemia and lower complications can help with the symptoms and complications of the disease in both children and adults. Blood and marrow stem cell transplants may offer a cure for a small number of people. 4|Page symptoms and lead normal lives. doctors have learned a great deal about sickle cell anemia. People who have the disease inherit two genes for sickle hemoglobin—one from each parent. They tend to block blood flow in the blood vessels of the limbs and organs. many people who have the disease can have improved quality of life and reasonable health much of the time. with proper care and treatment. Because of improved treatments and care. However. They know its causes. Sickle cell anemia varies from person to person. However. how it affects the body. People who have sickle cell trait usually have few. people who have sickle cell anemia are now living into their forties or fifties. Some people who have the disease have chronic (long-term) pain or fatigue (tiredness). 5|Page . What Causes Sickle Cell Anemia? Sickle cell anemia is an inherited disease. Sickle hemoglobin causes red blood cells to develop a sickle. Over the past 100 years. or crescent. It can also raise the risk for infection. Blocked blood flow can cause pain and organ damage. People who have sickle cell trait can pass the sickle hemoglobin gene to their children. or longer. if any. Sickle Cell Trait People who inherit a sickle hemoglobin gene from one parent and a normal gene from the other parent have sickle cell trait. shape. The following image shows an example of an inheritance pattern for sickle cell trait. and how to treat many of its complications. some people may have medical complications. Sickle cells are stiff and sticky. Their bodies make both sickle hemoglobin and normal hemoglobin. A person inherits two hemoglobin genes—one from each parent.Example of an Inheritance Pattern for Sickle Cell Trait The image shows how sickle hemoglobin genes are inherited. When both parents have a normal gene and an abnormal gene. A normal gene will make normal hemoglobin (A). Others have very severe symptoms and often are hospitalized for treatment. but many infants don't show any signs until after 4 months of age. The most common signs and symptoms are linked to anemia and pain. Sickle cell anemia is present at birth. each child has a 25 percent chance of inheriting two normal genes. A sickle hemoglobin gene will make abnormal hemoglobin (S). Some people have mild symptoms. 6|Page . a 50 percent chance of inheriting one normal gene and one abnormal What Are the Signs and Symptoms of Sickle Cell Anemia? The signs and symptoms of sickle cell anemia vary. Other signs and symptoms are linked to the disease's complications. Other signs and symptoms of anemia include: Shortness of breath Dizziness Headaches Coldness in the hands and feet Paler than normal skin or mucous membranes (the tissue that lines your nose. 7|Page . a second blood test is done to confirm the diagnosis. all States mandate testing for sickle cell anemia as part of their newborn screening programs. lungs. This allows the baby's doctor to get the test results as quickly as possible. In the United States. can detect whether he or she has sickle hemoglobin. Sickle cell crises often affect the bones. This doctor also can provide treatment for sickle cell disease if needed.Test results are sent to the doctor who ordered the test and to the baby's primary care doctor. abdomen. and other organs and body cavities) Jaundice (a yellowish color of the skin or whites of the eyes) Signs and Symptoms Related to Pain Sudden pain throughout the body is a common symptom of sickle cell anemia. A hematologist is a doctor who specializes in blood diseases and disorders. and joints. It's important to give the correct contact information to the hospital. The test can show whether a newborn infant has sickle hemoglobin.Signs and Symptoms Related to Anemia The most common symptom of anemia is fatigue (feeling tired or weak). The second test should be done as soon as possible and within the first few months of life. Health providers from a newborn screening followup program may contact you directly to make sure you're aware of the test results. How Is Sickle Cell Anemia Diagnosed? A simple blood test. The primary care doctor may send you to a hematologist for a second blood test. early diagnosis is very important.If the test shows some sickle hemoglobin. This pain is called a sickle cell crisis. mouth. However. The test uses blood from the same blood samples used for other routine newborn screening tests. done at any time during a person's lifespan. Doctors also can diagnose sickle cell disease before birth.)Testing before birth can be done as early as 10 weeks into the pregnancy. 8|Page . This testing looks for the sickle hemoglobin gene. rather than the abnormal hemoglobin that the gene makes. (Amniotic fluid is the fluid in the sac surrounding a growing embryo. This is done using a sample of amniotic fluid or tissue taken from the placenta. The placenta is the organ that attaches the umbilical cord to the mother's womb. andoxygen therapy (if the oxygen level is low). 9|Page . The goals of treating sickle cell anemia are to relieve pain. Blood and marrow stem cell transplants may offer a cure for a small number of people who have sickle cell anemia.How Is Sickle Cell Anemia Treated? Sickle cell anemia has no widely available cure. emergency room. and plenty of fluids. Treating Pain Medicines and Fluids Mild pain often is treated at home with over-the-counter pain medicines. These initial treatment steps have greatly improved the outcome for children who have sickle cell anemia. or hemoglobin F. or hospital. heating pads. Researchers continue to look for new treatments for the disease. Hydroxyurea Severe sickle cell anemia can be treated with a medicine called hydroxyurea. Fetal hemoglobin. Fluids help prevent dehydration. medicines. fetal hemoglobin helps prevent red blood cells from sickling and improves anemia. Hematologists specialize in treating adults and children who have blood diseases or disorders.Infants who have been diagnosed with sickle cell anemia through newborn screening are treated with antibiotics to prevent infections and receive needed vaccinations. The usual treatments for acute (rapid-onset) pain are fluids. More severe pain may need to be treated in a day clinic. Their parents are educated about the disease and how to manage it. Specialists Involved People who have sickle cell anemia need regular medical care. rest. organ damage. treatments can help relieve symptoms and treat complications. This medicine prompts your body to make fetal hemoglobin. Some doctors and clinics specialize in treating people who have the disease. However. prevent infections.In people who have sickle cell anemia. is the type of hemoglobin that newborns have. and strokes and control complications (if they occur). Fluids are given either by mouth or through a vein. a condition in which your body doesn't have enough fluids. Many people taking hydroxyurea also need fewerblood transfusions and have fewer hospital visits. such as stroke. Regular Health Care for Children Children who have sickle cell anemia need routine health care (just like children who don't have the disease). After age 2. Examples include allergic reactions and a dangerous buildup of iron in the body (which must be treated). Talk with your child's 10 | P a g e . Preventing Complications Blood transfusions are commonly used to treat worsening anemia and sickle cell complications. hydroxyurea reduces how often painful sickle cell crises and acute chest syndrome occur. All routine vaccinations (including a yearly flu shot). Some. but not all. Children who have sickle cell anemia may need even more checkups. the blood supply is fairly safe from infections such as hepatitis and HIV. people who have sickle cell anemia need regular blood transfusions to prevent life-threatening problems. Taken daily by mouth. They need to have their growth checked regularly. but they usually still need checkups at least every 6 months. All children younger than 2 years old should see their doctors often. Treatment may begin as early as 2 months of age and continue until the child is at least 5 years old. A sudden worsening of anemia due to an infection or enlarged spleen is a common reason for a blood transfusion. plus the pneumococcal vaccine. or acute chest syndrome. They also need to get the routine shots that all children get. Often. spleen problems. Infections Infections can be a major complication of sickle cell anemia throughout life. infections can be prevented or treated.These visits are a time for parents to talk with their child's doctor and ask questions about the child's care. Having routine blood transfusions can cause side effects. To prevent infections in babies and young children. children who have sickle cell anemia may not need to see their doctors as often. but especially during childhood. In general. treatments include: Daily doses of antibiotics. Until age 5. blood from babies' umbilical cords. Researchers want to know whether a normal gene can be put into the bone marrow stem cells of a person who has sickle cell anemia.Young children who have sickle cell anemia should have regular checkups with a hematologist (a blood specialist).doctor about eye checkups and whether your child needs an ultrasound scan of the brain. This treatment may even offer a cure for a small number of people. daily penicillin is given to most children who have sickle cell anemia. However. Researchers continue to look for sources of bone marrow stem cells—for example. Researchers also are looking for a way to predict the severity of the disease. the decision to give this treatment is made on a case-by-case basis. New Treatments Research on blood and marrow stem cell transplants. Doctors also give many children a vitamin called folic acid (folate) to help boost red blood cell production. gene therapy. The hope is that these studies will provide better treatments for the disease. This would cause the body to make normal red blood cells. This limits the number of people who may have a donor.The stem cells used for a transplant must come from a closely matched donor. Gene Therapy Gene therapy is being studied as a possible treatment for sickle cell anemia. They also continue to look for ways to reduce the risks of this procedure. and new medicines for sickle cell anemia is ongoing. The donor usually is a close family member who doesn't have sickle cell anemia. The transplant process is risky and can lead to serious side effects or even death. However.Blood and marrow stem cell transplants usually are used for young patients who have severe sickle cell anemia. Blood and Marrow Stem Cell Transplant A blood and marrow stem cell transplant can work well for treating sickle cell anemia. new transplant approaches may improve treatment for people who have sickle cell anemia and involve less risk. 11 | P a g e . People who are at high risk of having a child with sickle cell anemia and are planning to have children may want to consider genetic counseling. many people who have sickle cell anemia can live productive lives. Adenosine A2a receptor agonists: These medicines may reduce pain-related complications in people who have sickle cell anemia. and clinics that care for people who have sickle cell anemia. Fetal hemoglobin helps prevent red blood cells from sickling and improves anemia. Many people who have sickle cell anemia now live into their forties or fifties. If you have sickle cell anemia. They include: Decitabine: Like hydroxyurea. 5-HMF: This natural compound binds to red blood cells and increases their oxygen. How Can Sickle Cell Anemia Be Prevented? You can’t prevent sickle cell anemia. it's important to: Adopt or maintain a healthy lifestyle Take steps to prevent and control complications 12 | P a g e . this medicine prompts the body to make fetal hemoglobin. neighborhood health centers. steps should be taken to reduce complications. Decitabine might be used instead of hydroxyurea or added to hydroxyurea. Living With Sickle Cell Anemia With good health care. A counselor can explain the risk (likelihood) of having a child who has the disease. because it’s an inherited disease. If a person is born with it. They also can have reasonably good health much of the time and live longer today than in the past. This helps prevent the red blood cells from sickling. He or she also can help explain the choices that are available. You can find information about genetic counseling from health departments. medical centers. New Medicines Researchers are studying several medicines for sickle cell anemia. or longer. Researchers also are studying whether they can "turn off" the sickle hemoglobin gene or "turn on" a gene that makes red blood cells behave normally. About 8 out of 10 people who have hemophilia have type A. and elbows. you're missing or have low levels of clotting factor IX (9). clotting factors help platelets stick together to plug cuts and breaks on the vessels and stop bleeding. "Acquired” means you aren't born with the disorder. There are several types of clotting factors. ankles. you're missing or have low levels of clotting factor VIII (8). The antibodies can prevent the clotting factors from working. If you have hemophilia B. hemophilia can be acquired. If you have hemophilia A. you may bleed for a longer time than others after an injury. When blood vessels are injured. Learn ways to cope with pain. Clotting factor is a protein needed for normal blood clotting. Overview Hemophilia usually is inherited. These proteins work with platelets to help the blood clot. Platelets are small blood cell fragments that form in the bone marrow—a sponge-like tissue in the bones.People born with hemophilia have little or no clotting factor. Platelets play a major role in blood clotting. This can happen if your body forms antibodies (proteins) that attack the clotting factors in your bloodstream. You also may bleed inside your body (internally). but you develop it during your lifetime.The two main types of hemophilia are A and B. especially in your knees. 13 | P a g e . HEMOPHILIA What Is Hemophilia? Hemophilia is a rare bleeding disorder in which the blood doesn't clot normally. Rarely. If you have hemophilia. This bleeding can damage your organs and tissues and may be life threatening. "Inherited” means that the disorder is passed from parents to children through genes. you're born with the disorder. while males have one X and one Y chromosome.What Causes Hemophilia? If you have inherited hemophilia. These genes are located on the X chromosomes. A male who has a faulty hemophilia gene on his X chromosome will have hemophilia. It's caused by a defect in one of the genes that determine how the body makes blood clotting factor VIII or IX. If a female has the faulty gene on only one of her 14 | P a g e . A female must have the faulty gene on both of her X chromosomes to have hemophilia. which is very rare. Only the X chromosome carries the genes related to clotting factors. Chromosomes come in pairs. Females have two X chromosomes. Below are two examples of how the hemophilia gene is inherited. he has two normal chromosomes —X and Y). The mother is a carrier of hemophilia (that is.” Carriers don't have hemophilia. but they can pass the faulty gene to their children. the father doesn't have hemophilia (that is. she is a "hemophilia carrier. Inheritance Pattern for Hemophilia— Example 1 The image shows one example of how the hemophilia gene is inherited.X chromosomes. Each daughter has a 50 percent chance of inheriting the faulty gene from her mother and being a carrier. In this example. 15 | P a g e . Each son has a 50 percent chance of inheriting the faulty gene from his mother and having hemophilia. she has one faulty X chromosome and one normal X chromosome). However. 16 | P a g e . the father has hemophilia (that is. The mother isn't a hemophilia carrier (that is. Very rarely. Some males who have the disorder are born to mothers who aren't carriers. she has two normal X chromosomes). a girl is born with hemophilia. In these cases. In this example. thus. This can happen if her father has hemophilia and her mother is a carrier. Each daughter will inherit the faulty gene from her father and be a carrier. up to 50 percent of carriers may have an increased risk of bleeding. None of the sons will inherit the faulty gene from their father. Females who are hemophilia carriers usually have enough clotting factors from their one normal X chromosome to prevent serious bleeding problems. none will have hemophilia. a mutation occurs in the gene as it is passed to the child.Inheritance Pattern for Hemophilia—Example 2 The image shows one example of how the hemophilia gene is inherited. his X chromosome is faulty). Signs of external bleeding may include: Bleeding in the mouth from a cut or bite or from cutting or losing a tooth Nosebleeds for no obvious reason Heavy bleeding from a minor cut Bleeding from a cut that resumes after stopping for a short time Signs of internal bleeding may include: Blood in the urine (from bleeding in the kidneys or bladder) Blood in the stool (from bleeding in the intestines or stomach) Large bruises (from bleeding into the large muscles of the body) Bleeding in the Joints Bleeding in the knees. Pain can be severe. the bleeding causes tightness in the joint with no real pain or any visible signs of bleeding.What Are the Signs and Symptoms of Hemophilia? The major signs and symptoms of hemophilia are excessive bleeding and easy bruising. an accident. elbows. or other joints is another common form of internal bleeding in people who have hemophilia. hot to touch. 17 | P a g e . Excessive Bleeding The extent of bleeding depends on how severe the hemophilia is. Joint bleeding that isn't treated quickly can damage the joint. Swelling continues as bleeding continues. The joint then becomes swollen. or surgery. Eventually. movement in the joint is temporarily lost.At first. Children who have mild hemophilia may not have signs unless they have excessive bleeding from a dental procedure. and painful to bend. This bleeding can occur without obvious injury. Bleeding can occur on the body's surface (external bleeding) or inside the body (internal bleeding). painful headaches or neck pain or stiffness Repeated vomiting Sleepiness or changes in behavior Sudden weakness or clumsiness of the arms or legs or problems walking Double vision Convulsions or seizures How Is Hemophilia Diagnosed? If you appear to have a bleeding problem. and how severe it is. or severe. including women and girls.Bleeding in the Brain Internal bleeding in the brain is a very serious complication of hemophilia. Mild hemophilia 5–40 percent of normal clotting factor Moderate hemophilia 1–5 percent of normal clotting factor Severe hemophilia Less than 1 percent of normal clotting factor 18 | P a g e . However. what type of hemophilia you have. It can happen after a simple bump on the head or a more serious injury. depending on the amount of clotting factor VIII or IX in the blood. some people who have hemophilia have no recent family history of the disease. have bleeding problems. your doctor will ask about your personal and family medical histories. Blood tests are used to find out: How long it takes for your blood to clot Whether your blood has low levels of any clotting factors Whether any clotting factors are completely missing from your blood The test results will show whether you have hemophilia. The signs and symptoms of bleeding in the brain include: Long-lasting. Hemophilia A and B are classified as mild. You or also will likely have a physical exam and blood tests to diagnose hemophilia. moderate. This will reveal whether you or your family members. Von Willebrand factor carries and binds factor VIII. The blood is treated to prevent the spread of diseases. such as hepatitis. which can then stay in the bloodstream longer. Concentrates of clotting factor VIII (for hemophilia A) or clotting factor IX (for hemophilia B) are slowly dripped or injected into a vein. 19 | P a g e . DDAVP isn't used to treat hemophilia B or severe hemophilia A. With the current methods of screening and treating donated blood. muscles. Clotting factor concentrates can be made from human blood. DDAVP stimulates the release of stored factor VIII and von Willebrand factor.How Is Hemophilia Treated? Treatment With Replacement Therapy The main treatment for hemophilia is called replacement therapy. These infusions help replace the clotting factor that's missing or low. Complications of Replacement Therapy Complications of replacement therapy include: Developing antibodies (proteins) that attack the clotting factor Developing viral infections from human clotting factors Damage to joints. the risk of getting an infectious disease from human clotting factors is very small. or other parts of the body resulting from delays in treatment Other Types of Treatment Desmopressin Desmopressin (DDAVP) is a man-made hormone used to treat people who have mild hemophilia A. it also increases the level of these proteins in your blood. DDAVP usually is given by injection or as nasal spray. For example. the medicine is given only in certain situations. you may take this medicine prior to dental work or before playing certain sports to prevent or reduce bleeding. Because the effect of this medicine wears off if it's used often. you'll need care if you have: 20 | P a g e . Know the signs and symptoms of bleeding in joints and other parts of the body. steroids. gym trainer. Talk with your doctor or pharmacist about which medicines are safe for you to take. These medicines most often are used before dental work or to treat bleeding from the mouth or nose or mild intestinal bleeding. They're usually given as a pill. Gene Therapy Researchers are trying to find ways to correct the faulty genes that cause hemophilia. and sports coach about your condition.Antifibrinolytic Medicines Antifibrinolytic medicines (including tranexamic acid and epsilon aminocaproic acid) may be used with replacement therapy. Tell all of your health care providers—such as your doctor. Dentists at the HTCs are experts in providing dental care for people who have hemophilia. and pharmacist—that you have hemophilia. However. Know when to call your doctor or go to the emergency room. If you see another dentist. The dentist can provide medicine that will reduce bleeding during dental work. For example: Follow your treatment plan exactly as your doctor prescribes. Have regular checkups and vaccinations as recommended. dentist. you can take steps to avoid complications. tell him or her that you have hemophilia. Ongoing Care If you have hemophilia. Treatment of a Specific Bleeding Site Pain medicines. researchers continue to test gene therapy in clinical trial. For example. You also may want to tell people like your employee health nurse. and physical therapy may be used to reduce pain and swelling in an affected joint. Gene therapy hasn't yet developed to the point that it's an accepted treatment for hemophilia. Have regular dental care. and they help keep blood clots from breaking down. watery substance. sinuses.)The buildup of mucus makes it easy for bacteria to grow. serious lung infections. As a result. o Heavy bleeding that can't be stopped or a wound that continues to ooze blood. People who have CF inherit two faulty genes for the disease—one from each parent. The thick. your mucus becomes thick and sticky. The parents likely don't have the disease themselves. It's a good idea to keep a record of all previous treatments. Overview Mucus is a substance made by tissues that line some organs and body cavities. such as the lungs and nose. pancreas. Such bleeding is life threatening and requires emergency care. CF mainly affects the lungs. It keeps the linings of certain organs moist and prevents them from drying out or getting infected. This leads to repeated. and sex organs. the digestive enzymes that your pancreas makes can't reach your small intestine. in your pancreas (an organ in your abdomen). 21 | P a g e . pain. Normally. CYSTIC FIBROSIS What Is Cystic Fibrosis? Cystic fibrosis is an inherited disease of the secretory glands. "Inherited" means the disease is passed from parents to children through genes. or ducts. It builds up in your lungs and blocks your airways. o Limited motion. sticky mucus also can block tubes. Over time. intestines. o Any signs or symptoms of bleeding in the brain. liver. mucus is a slippery. If you have CF. (Airways are tubes that carry air in and out of your lungs. Be sure to take this information with you to medical appointments and to the hospital or emergency room. Secretory glands include glands that make mucus and sweat. these infections can severely damage your lungs. or swelling of any joint. This gene makes a protein that controls the movement of salt and water in and out of your body's cells. when you sweat. fatigue (tiredness). death. If you or your child has the disease. a swollen belly from severe constipation. Sometimes you'll have few symptoms. Today. you'll have more severe symptoms more often. Examples of these problems include dehydration (a lack of fluid in your body). exercise. In 22 | P a g e . some people who have CF are living into their forties or fifties. your symptoms may become more severe. you're also at higher risk for diabetes or two bone- thinning conditions called osteoporosis and osteopenia. you may have serious lung and digestive problems. and the disease can make it harder for women to get pregnant. CF also causes your sweat to become very salty. heat stroke. symptoms may not show up until the teen or adult years. As the disease gets worse. Treatments may include nutritional and respiratory therapies. If you or your child has CF. you lose large amounts of salt. If the disease is mild. Without them. rarely. Outlook The symptoms and severity of CF vary.CF also causes infertility in men. intestinal gas. Lung function often starts to decline in early childhood in people who have CF. You also may have bulky stools. and other treatments. This can upset the balance of minerals in your blood and cause many health problems. and.Your doctor also may recommend pulmonary rehabilitation (PR). Thus. medicines. or longer. What Causes Cystic Fibrosis? A defect in the CFTR gene causes cystic fibrosis (CF). weakness. decreased blood pressure. so does life expectancy for those who have the disease. increased heart rate.As treatments for CF continue to improve. This can cause vitamin deficiency and malnutrition because nutrients pass through your body without being used. Other times. The symptoms and severity of CF also vary over time. your intestines can't fully absorb fats and proteins. and pain or discomfort. Respiratory failure is the most common cause of death in people who have CF. Over time. damage to the lungs can cause severe breathing problems. PR is a broad program that helps improve the well-being of people who have chronic breathing problems. Early treatment for CF can improve your quality of life and increase your lifespan. These enzymes help break down food. Children who inherit one faulty CFTR gene and one normal CFTR gene are "CF carriers. sticky mucus and very salty sweat.More than a thousand known defects can affect the CFTR gene. Other genes also may play a role in the severity of the disease. This causes thick. Children who inherit a faulty CFTR gene from each parent will have CF. the gene makes a protein that doesn't work well. This may help explain other symptoms and complications of CF. they can pass the faulty CFTR gene to their children. The type of defect you or your child has may affect the severity of CF. 23 | P a g e . How Is Cystic Fibrosis Inherited? Every person inherits two CFTR genes—one from each parent.people who have CF." CF carriers usually have no symptoms of CF and live normal lives. However. Research suggests that the CFTR protein also affects the body in other ways. A person inherits two copies of the CFTR gene—one from each parent. Who Is at Risk for Cystic Fibrosis? Cystic fibrosis (CF) affects both males and females and people from all racial and ethnic groups. The image below shows how two parents who are both CF carriers can pass the faulty CFTR gene to their children. a 50 percent chance of inheriting one normal gene and one faulty gene. 24 | P a g e . If each parent has a normal CFTR gene and a faulty CFTR gene. and a 25 percent chance of inheriting two faulty genes. The disease is less common among African Americans and Asian Americans. However. the disease is most common among Caucasians of Northern European descent. Example of an Inheritance Pattern for Cystic Fibrosis The image shows how CFTR genes are inherited. each child has a 25 percent chance of inheriting two normal genes. CF also is common among Latinos and American Indians. especially the Pueblo and Zuni. Many of them don't know that they're CF carriers. or the baby doesn't pass stool when first born. One of the first signs of CF that parents may notice is that their baby's skin tastes salty when kissed. Cystic Fibrosis Figure A shows the organs that cystic fibrosis can affect. Other times. The widened airway is blocked by thick. digestive. your symptoms may become more severe. What Are the Signs and Symptoms of Cystic Fibrosis? The signs and symptoms of cystic fibrosis (CF) vary from person to person and over time. sticky mucus that contains blood and bacteria. 25 | P a g e .More than 10 million Americans are carriers of a faulty CF gene. Sometimes you'll have few symptoms. Figure B shows a cross- section of a normal airway. They're related to how CF affects the respiratory. or reproductive systems of the body. Most of the other signs and symptoms of CF happen later. Figure C shows an airway with cystic fibrosis. Infections can block the airways and cause frequent coughing that brings up thick sputum (spit) or mucus that's sometimes bloody. sticky mucus that builds up in their airways. High salt levels confirm a diagnosis of CF. The blood test shows whether a newborn's pancreas is working properly. He or she rubs the skin with a sweat-producing chemical and then uses an electrode to provide a mild electrical current. It can lead to bone-thinning disorders called osteoporosis and osteopenia. CF also can cause clubbing and low bone density. A sweat test measures the amount of salt in sweat. a doctor will confirm the diagnosis using a sweat test. For this test. the doctor triggers sweating on a small patch of skin on an arm or leg. Sweat Test If a genetic test or blood test suggests CF. Newborn Screening All States screen newborns for CF using a genetic test or a blood test. The genetic test shows whether a newborn has faulty CFTR genes. This test is the most useful test for diagnosing CF. This buildup of mucus makes it easier for bacteria to grow and cause infections. This sign develops late in CF because your lungs aren't moving enough oxygen into your bloodstream. The goals of CF treatment include: Preventing and controlling lung infections 26 | P a g e . treatments have greatly improved in recent years.Respiratory system signs and symptoms People who have CF have thick. Sweat is collected on a pad or paper and then analyzed. How Is Cystic Fibrosis Treated? Cystic fibrosis (CF) has no cure. How Is Cystic Fibrosis Diagnosed? Doctors diagnose cystic fibrosis (CF) based on the results from various tests. This may cause a tingling or warm feeling.Low bone density also tends to occur late in CF. Clubbing is the widening and rounding of the tips of your fingers and toes. The sweat test usually is done twice. However. If you exercise regularly. CF causes your sweat to become very salty. bronchodilators. 27 | P a g e . and thin mucus. your doctor may prescribe antibiotics. anti-inflammatory medicines. Chest Physical Therapy CPT also is called chest clapping or percussion. As a result. Your doctor also may recommend apulmonary rehabilitation (PR) program. Treatment for Lung Problems The main treatments for lung problems in people who have CF are chest physical therapy (CPT). sticky mucus from the lungs Preventing or treating blockages in the intestines Providing enough nutrition Preventing dehydration (a lack of fluid in the body) Depending on the severity of CF. you should check with your doctor first. you or your child may be treated in a hospital. you may be able to cut back on your CPT. reduce swelling and open up the airways. or medicines to help clear the mucus. Exercise Aerobic exercise that makes you breathe harder can help loosen the mucus in your airways so you can cough it up. which occurs in about 5 percent of people who have CF. your body loses large amounts of salt when you sweat. your doctor may recommend a high- salt diet or salt supplements to maintain the balance of minerals in your blood. exercise. However. However. These medicines help treat or prevent lung infections. It involves pounding your chest and back over and over with your hands or a device to loosen the mucus from your lungs so that you can cough it up. your doctor may prescribe the oral medicine ivacaftor (approved for people with CF who are 6 years of age and older). and medicines. If you have mutations in a gene called G551D. Thus. Loosening and removing thick. Exercise also helps improve your overall physical condition. Medicines If you have CF. It can improve your ability to function and your quality of life. Even if you have advanced lung disease. you can still benefit from PR. inhaled. severe constipation. 28 | P a g e . Antibiotics are the main treatment to prevent or treat lung infections. Oxygen usually is given through nasal prongs or a mask. Digestive problems also can lead to poor growth and development in children. such as bulky stools. PR doesn't replace medical therapy. you may need oxygen therapy. it's used with medical therapy and may include: Exercise training Nutritional counseling Education on your lung disease or condition and how to manage it Energy-conserving techniques Breathing strategies Psychological counseling and/or group support PR has many benefits. If other treatments haven't worked. Instead. a lung transplant may be an option if you have severe lung disease. Your doctor may prescribe oral. a swollen belly. PR is a broad program that helps improve the well-being of people who have chronic (ongoing) breathing problems. A lung transplant is surgery to remove a person's diseased lung and replace it with a healthy lung from a deceased donor. Pulmonary Rehabilitation Your doctor may recommend PR as part of your treatment plan. Treatments for Advanced Lung Disease If you have advanced lung disease. The program also may help relieve your breathing problems. and pain or discomfort. or intravenous (IV) antibiotics. intestinal gas. Treatment for Digestive Problems CF can cause many digestive problems. A healthy diet includes a variety of fruits. Work closely with your doctors to learn how to manage CF. Living With Cystic Fibrosis If you or your child has cystic fibrosis (CF). Your doctor may prescribe medicines that prevent your bones from losing their density. Another common CF complication is the bone-thinning disorder osteoporosis. you can practice good self-care and follow a healthy lifestyle. For example. and whole grains. vegetables. Other lifestyle changes include: Not smoking and avoiding tobacco smoke Washing your hands often to lower your risk of infection Exercising regularly and drinking lots of fluids Doing chest physical therapy (as your doctor recommends) 29 | P a g e . you should learn as much as you can about the disease. Talk with your doctor about what types and amounts of foods you should include in your diet. follow a healthy diet.Treatments for Cystic Fibrosis Complications A common complication of CF is diabetes. The type of diabetes associated with CF often requires different treatment than other types of diabetes. Lifestyle Changes In between medical checkups. If more than two genes are missing. The severity of beta thalassemia depends on how much one or both genes are affected. It carries oxygen to all parts of the body. also called hemoglobin A. "Inherited" means that the disorder is passed from parents to children through genes. Doctors diagnose thalassemias using blood tests. Greek. Overview Normal hemoglobin. has four protein chains—two alpha globin and two beta globin. alpha and beta. Anemia is caused by a lower than normal number of red blood cells or not enough hemoglobin in the red blood cells. Hemoglobin is an iron-rich protein in red blood cells. The two major types of thalassemia. The severe form of beta thalassemia is known as thalassemia major or Cooley's anemia. Thalassemias cause the body to make fewer healthy red blood cells and less hemoglobin than normal.THALASSEMIA What Are Thalassemias? Thalassemias are inherited blood disorders. and African descent. Thalassemias affect males and females. Babies who have this disorder usually die before or shortly after birth. The disorders are treated withblood transfusions. Severe forms usually are diagnosed in early childhood and are lifelong conditions. Two genes (one from each parent) are needed to make enough beta globin protein chains. Southern Asian. People who have thalassemias can have mild or severe anemia. Middle Eastern. where it's exhaled. Hemoglobin also carries carbon dioxide (a waste gas) from the body to the lungs. Beta thalassemia occurs if one or both genes are altered. The most severe form of alpha thalassemia is called alpha thalassemia major or hydrops fetalis. moderate to severe anemia occurs. are named after defects in these protein chains. Four genes (two from each parent) are needed to make enough alpha globin protein chains. The disorders occur most often among people of Italian. Alpha thalassemia trait occurs if one or two of the four genes are missing. medicines. Outlook 30 | P a g e . the result is moderate to severe anemia. and other procedures. If both genes are affected. People who have moderate to severe forms of thalassemia have inherited faulty genes from both parents. an iron-rich protein that carries oxygen from your lungs to all parts of your body. Thalassemias are inherited disorders—that is. Hemoglobin has two kinds of protein chains: alpha globin and beta globin. 31 | P a g e . they're passed from parents to children through genes. This means you won't have any signs of illness. If you're only missing one gene. Carriers often have no signs of illness other than mild anemia. Red blood cells contain hemoglobin. complications from thalassemias and their treatments are frequent. If one or more of the genes is missing. However. and platelets. However. Your body won't work well if your red blood cells don't make enough healthy hemoglobin. thalassemias occur. They need to take care of themselves to remain as healthy as possible. where it's exhaled. Alpha Thalassemias You need four genes (two from each parent) to make enough alpha globin protein chains. People who have moderate or severe thalassemias must closely follow their treatment plans. This means that your body doesn't make enough alpha globin protein. Treatments for thalassemias have improved over the years. red blood cells won't form correctly or carry enough oxygen. you're a "silent" carrier. What Causes Thalassemias? Your body makes three types of blood cells: red blood cells. People who inherit faulty hemoglobin genes from one parent but normal genes from the other are called carriers. You may have mild anemia. they can pass the faulty genes on to their children. Hemoglobin also carries carbon dioxide (a waste gas) from your body to your lungs. white blood cells. If your body doesn't make enough of these protein chains or they're abnormal. you have alpha thalassemia trait (also called alpha thalassemia minor). When these genes are missing or altered. you'll have alpha thalassemia trait or disease. People who have moderate or severe thalassemias are now living longer and have better quality of life. If you're missing two genes. Genes control how the body makes hemoglobin protein chains. The alpha globin genes are located on chromosome 16. A child inherits four alpha globin genes (two from each parent). Each child has a 25 percent chance of inheriting two missing genes and two normal genes (thalassemia trait). you likely have hemoglobin H disease (which a blood test can detect). This form of thalassemia causes moderate to severe anemia. the father is missing two alpha globin genes and the mother is missing one alpha globin gene. This condition is called alpha thalassemia major or hydrops fetalis. Very rarely. three missing genes and one normal gene 32 | P a g e . Babies who have hydrops fetalis usually die before or shortly after birth. If you're missing three genes. In this example. Example of an Inheritance Pattern for Alpha Thalassemia The picture shows one example of how alpha thalassemia is inherited. a baby is missing all four genes. If both genes are altered. This condition is called beta thalassemia trait or beta thalassemia minor. you'll have beta thalassemia.(hemoglobin H disease). This means that your body won’t make enough beta globin protein. The beta globin gene is located on chromosome 11. Example of an Inheritance Pattern for Beta Thalassemia The picture shows one example of how beta thalassemia is inherited. four normal genes (no anemia). The intermedia form of the disorder causes moderate anemia. If you have one altered gene. A child inherits two beta globin genes (one from each parent). you're a carrier. It causes mild anemia. Beta Thalassemias You need two genes (one from each parent) to make enough beta globin protein chains. The major form causes severe anemia. each parent has one altered beta globin gene. In this example. 33 | P a g e . If one or both of these genes are altered. or one missing gene and three normal genes (silent carrier). you'll have beta thalassemia intermedia or beta thalassemia major (also called Cooley's anemia). If your parents have missing or altered hemoglobin-making genes. Each child has a 25 percent chance of inheriting two normal genes (no anemia). or a 25 percent chance of inheriting two altered genes (beta thalassemia major). you may have thalassemia. the genes for the disorders are passed from parents to their children. Ancestry 34 | P a g e . Who Is at Risk for Thalassemias? Family history and ancestry are the two risk factors for thalassemias. Family History Thalassemias are inherited—that is. a 50 percent chance of inheriting one altered gene and one normal gene (beta thalassemia trait). and African descent. Thalassemias occur most often among people of Italian. No Symptoms Alpha thalassemia silent carriers generally have no signs or symptoms of the disorder. The lack of oxygen occurs because the body doesn't make enough healthy red blood cells and hemoglobin. The lack of alpha globin protein is so minor that the body's hemoglobin works normally. 35 | P a g e . The severity of symptoms depends on the severity of the disorder. What Are the Signs and Symptoms of Thalassemias? A lack of oxygen in the bloodstream causes the signs and symptoms of thalassemias. Southern Asian. Middle Eastern. Greek. the spleen has to work very hard. They may become brittle and break easily. However.Mild anemia caused by alpha thalassemia trait might be mistaken for iron-deficiency anemia. it must be removed. An enlarged spleen. Bone marrow is the spongy substance inside bones that makes blood cells. The spleen is an organ that helps your body fight infection and remove unwanted material. the bones become wider than normal. This makes anemia worse. many people who have these types of thalassemia have no signs or symptoms. As a result.Mild Anemia People who have alpha or beta thalassemia trait can have mild anemia. . When bone marrow expands. such as: Slowed growth and delayed puberty. 36 | P a g e . They also may have other health problems. Bone problems. Mild anemia can make you feel tired. When a person has thalassemia. Thalassemia may cause bone marrow to expand. Anemia can slow down a child's growth and development. the spleen becomes larger than normal. If the spleen becomes too large. Mild to Moderate Anemia and Other Signs and Symptoms People who have beta thalassemia intermedia have mild to moderate anemia. arrhythmias (irregular heartbeats). Infection Among people who have thalassemias. Heart disease caused by iron overload is the main cause of death in people who have thalassemias. or heart Bone problems (especially with bones in the face) Complications of Thalassemias Better treatments now allow people who have moderate and severe thalassemias to live much longer. and heart attack. Transfusions can cause iron to build up in the blood (iron overload). such as: A pale and listless appearance Poor appetite Dark urine (a sign that red blood cells are breaking down) Slowed growth and delayed puberty Jaundice (a yellowish color of the skin or whites of the eyes) An enlarged spleen. infections are a key cause of illness and the second most common cause of death. Heart and Liver Diseases Regular blood transfusions are a standard treatment for thalassemias. People who have had their spleens removed are at even higher risk because they no longer have this infection-fighting organ. Heart disease includes heart failure.Severe Anemia and Other Signs and Symptoms People who have hemoglobin H disease or beta thalassemia major (also called Cooley's anemia) have severe thalassemia. especially the heart and liver. these people must cope with complications of these disorders that occur over time. liver. 37 | P a g e . Signs and symptoms usually occur within the first 2 years of life. They may include severe anemia and other health problems. As a result. This can damage organs and tissues. They’ll likely need little or no treatment. including a complete blood count (CBC) and special hemoglobin tests. Doctors use three standard treatments for moderate and severe forms of thalassemia. A CBC measures the amount of hemoglobin and the different kinds of blood cells. in a sample of blood. such as red blood cells. including osteoporosis. These treatments include blood transfusions. enjoy normal activities. How Are Thalassemias Diagnosed? Doctors diagnose thalassemias using blood tests. People who have thalassemias have problems with the alpha or beta globin protein chains of hemoglobin. Hemoglobin tests measure the types of hemoglobin in a blood sample. How Are Thalassemias Treated? Treatments for thalassemias depend on the type and severity of the disorder. but it's expensive and carries a risk of 38 | P a g e . People who have alpha or beta thalassemia trait may have red blood cells that are smaller than normal. and live into adulthood. Other treatments have been developed or are being tested. but they're used much less often. People who have thalassemias have fewer healthy red blood cells and less hemoglobin than normal in their blood.Osteoporosis Many people who have thalassemias have bone problems. This treatment gives you healthy red blood cells with normal hemoglobin. iron chelation therapy. and folic acid supplements. Blood transfusions allow you to feel better. People who are carriers or who have alpha or beta thalassemia trait have mild or no symptoms. This is a condition in which bones are weak and brittle and break easily. Standard Treatments Blood Transfusions Transfusions of red blood cells are the main treatment for people who have moderate or severe thalassemias. This treatment is lifesaving. To prevent this damage. heart. diarrhea. the risk is very low in the United States because of careful blood screening. and tiredness. usually with a small portable pump used overnight. Folic Acid Supplements Folic acid is a B vitamin that helps build healthy red blood cells. Your doctor may recommend folic acid supplements in addition to treatment with blood transfusions and/or iron chelation therapy.transmitting infections and viruses (for example. but they're used much less often. Side effects include problems with vision and hearing. Two medicines are used for iron chelation therapy. A stem cell transplant is the only treatment that can cure thalassemia. But only a small number of people who have severe thalassemias are able to find a good donor match and have the risky procedure. This therapy takes time and can be mildly painful. joint pain. Stem cells are the cells inside bone marrow that make red blood cells and other types of blood cells. Blood and Marrow Stem Cell Transplant A blood and marrow stem cell transplant replaces faulty stem cells with healthy ones from another person (a donor). Iron Chelation Therapy The hemoglobin in red blood cells is an iron-rich protein. nausea (feeling sick to the stomach). This condition is called iron overload. regular blood transfusions can lead to a buildup of iron in the blood. It damages the liver. vomiting. hepatitis). Side effects include headache. 39 | P a g e . Thus. and other parts of the body. Deferasirox is a pill taken once daily. However. doctors use iron chelation therapy to remove excess iron from the body. Other Treatments Other treatments for thalassemias have been developed or are being tested. Deferoxamine is a liquid medicine that's given slowly under the skin. Living With Thalassemias Survival and quality of life have improved for people who have moderate or severe thalassemias. For example. However. However. Living with thalassemia can be challenging. Blood screening has reduced the number of infections from blood transfusions. This will allow people who have thalassemias to make their own healthy red blood cells and hemoglobin. After birth. Iron chelation treatments are available that are easier for some people to take. Making more fetal hemoglobin might make up for the lack of healthy adult hemoglobin. How Can Thalassemias Be Prevented? You can’t prevent thalassemias because they’re inherited (passed from parents to children through genes). it might be possible someday to insert a normal hemoglobin gene into stem cells in bone marrow. Follow Your Treatment Plan Following the treatment plan your doctor gives you is important. prenatal tests can detect these blood disorders before birth. don't stop taking your medicine.Possible Future Treatments Researchers are working to find new treatments for thalassemias. Some people have been cured through blood and marrow stem cell transplants. and take your iron chelation medicine as prescribed. Researchers also are studying ways to trigger a person's ability to make fetal hemoglobin after birth. This is because: More people are able to get blood transfusions now. but several approaches can help you cope. The leading cause of death among people who have 40 | P a g e . For example. treatments for other kinds of infections have improved. This type of hemoglobin is found in fetuses and newborns. Also. the body switches to making adult hemoglobin. get blood transfusions as your doctor recommends. Iron chelation treatment can take time and be mildly painful. and get any tests that your doctor recommends. genetic tests. Take Steps To Stay Healthy Take steps to stay as healthy as possible. talk with your doctor about whether you need other vitamin or mineral supplements. Follow a healthy eating plan and your doctor's instructions for taking iron supplements. such as vitamins A. liver. hepatitis B and C and HIV) Yearly tests to check for iron buildup in your liver Yearly vision and hearing tests Regular checkups to make sure blood transfusions are working Other tests as needed (such as lung function tests.thalassemias is heart disease caused by iron overload. C. The checkups include a physical exam. These tests may include: Monthly complete blood counts and tests for blood iron levels every 3 months Yearly tests for heart function. and tests to match your tissues with a possible donor if a stem cell transplant is being considered) Children who have thalassemias should receive yearly checkups to monitor their growth and development. 41 | P a g e . and any necessary tests. Get Ongoing Medical Care Keep your scheduled medical appointments. liver function. Also. or D or selenium. including a height and weight check. Folic acid is a B vitamin that helps build healthy red blood cells. Take folic acid supplements if your doctor prescribes them. Iron buildup can damage your heart. and viral infections (for example. and other organs. Watch for signs of infection (such as a fever) and take steps to lower your risk for infection (especially if you've had your spleen removed). Avoid crowds during cold and flu season. Call your doctor if a fever develops. Get vaccinations as needed. Your doctor will advise you about which vaccines you need. Keep the skin around the site where you get blood transfusions as clean as possible. You may need vaccines for the flu. hepatitis B. and meningitis. pneumonia. 42 | P a g e . For example: Wash your hands often. especially if you've had your spleen removed.
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