Hemophilia is not one disease but rather one of a group of inherited bleeding disorders that cause abnormal or exaggerated bleeding and poor blood clotting. The term is most commonly used to refer to two specific conditions known as hemophilia A and hemophilia B, which will be the main subjects of this article. Hemophilia A and B are distinguished by the specific gene that is mutated (altered to become defective) and codes for a defective clotting factor (protein) in each disease. Rarely, hemophilia C (a deficiency of Factor XI) is encountered, but its effect on clotting is far less pronounced than A or B.Hemophilia A and B are inherited in an X-linked recessive genetic pattern and are therefore much more common in males. This pattern of inheritance means that a given gene on the X chromosome expresses itself only when there is no normal gene present. For example, a boy has only one X chromosome, so a boy with hemophilia has the defective gene on his sole X chromosome (and so is said to be hemizygous for hemophilia). Hemophilia is the most common X-linked genetic disease.Although it is much rarer, a girl can have hemophilia, but she would have to have the defective gene on both of her X chromosomes or have one hemophilia gene plus a lost or defective copy of the second X chromosome that should be carrying the normal genes. If a girl has one copy of the defective gene on one of her X chromosomes and a normal second X chromosome, she does not have hemophilia but is said to be heterozygous for hemophilia (a carrier). Her male children have a 50% chance of inheriting the one mutated X gene and thus have a 50% chance of inheriting hemophilia from their carrier mother.Hemophilia A occurs in about 1 out of every 5000 live male births. Hemophilia A and B occurs in all racial groups. Hemophilia A is about four times more common than B. B occurs in about 1 out of 20- 30,000 live male births.Hemophilia has been called the Royal Disease because Queen Victoria, Queen of England from 1837 to 1901, was a carrier. Her daughters passed the mutated gene on to members of the royal families of Germany, Spain, and Russia. Alexandra, Queen Victoria's granddaughter, who became Tsarina of Russia in the early 20th century when she married Tsar Nicholas II, was a carrier. Their son, the Tsarevich Alexei, suffered from hemophilia.

Since men with the genetic mutation will have hemophilia, a man who does not have the condition cannot be a carrier of the disease. A woman who has a son with known hemophilia is termed an obligate carrier, and no testing is needed to establish that she is a carrier of hemophilia. Women whose carrier status is unknown can be evaluated either by testing for the clotting factors or by methods to characterize the mutation in the DNA. The DNA screening methods are generally the most reliable. Prenatal diagnosis is also possible with DNA-based tests performed on a sample obtained through amniocentesis or chorionic villus sampling. Most individuals are seen and tested by consultants who specialize in genetically linked diseases.

A major complication of treatment is the development of so-called inhibitors to the clotting factors. Inhibitors (antibodies) are produced because the body sees the factor concentrates used to treat patients to reduce or prevent bleeding, as foreign and activates an immune response in the patient to destroy the foreign substances (factor VIII or factor IX). Inhibitors to factor VIII are the most common and occur in about one-third of those with severe hemophilia A and about 1 out of every 50 people with mild or moderate hemophilia A. They typically develop in childhood in those with severe hemophilia A and later in life in milder cases. Inhibitors destroy both the replacement factor VIII concentrates as well as any factor VIII that is present in the body. This is a serious complication of treatment because the factor concentrates are no longer effective in treating the condition. The action of inhibitors to destroy factor VIII concentrates shows different degrees of severity among individuals and can even vary over time in the same individual. In about two-thirds of cases, the inhibitors disappear on their own or with treatment known as immune tolerance therapy (ITT) or immune tolerance induction (ITI). In cases of severe hemophilia A with persistence of inhibitors, other factor concentrates, such as activated prothrombin complex concentrate or recombinant factor VIIa, are administered to attempt to help control bleeding. The development of inhibitors to factor IX is much less common and occurs in about 1% of those with hemophilia B. However, these can cause a very serious allergic reaction when factor IX concentrates are given. Immune tolerance therapy to eliminate inhibitors is less successful than with hemophilia A.

Anyone can get hepatitis A, but those more likely to are people who <ul> <li>travel to developing countries</li> <li>live with someone who currently has an active hepatitis A infection</li> <li>use illegal drugs, including noninjection drugs</li> <li>have unprotected sex with an infected person</li> <li>provide child care</li> </ul> Also, men who have sex with men are more likely to get hepatitis A.

<ul> <li> Readers Comments 2 </li> <li> Share Your Story </li> </ul> Most people do not have any symptoms of hepatitis A. If symptoms of hepatitis A occur, they include <ul> <li>feeling tired</li> <li>muscle soreness</li> <li>upset stomach</li> <li>fever</li> <li>loss of appetite</li> <li>stomach pain</li> <li>diarrhea</li> <li>dark-yellow urine</li> <li>light-colored stools</li> <li>yellowish eyes and skin, called jaundice</li> </ul> Symptoms of hepatitis A can occur 2 to 7 weeks after coming into contact with the virus. Children younger than age 6 may have no symptoms. Older children and adults often get mild, flulike symptoms. See a doctor right away if you or a child in your care has symptoms of hepatitis A.

<ul> <li> Readers Comments 1 </li> <li> Share Your Story </li> </ul> Hepatitis A usually gets better in a few weeks without treatment. However, some people can have symptoms for up to 6 months. Your doctor may suggest medicines to help relieve your symptoms. Talk with your doctor before taking prescription and over-the-counter medicines. See your doctor regularly to make sure your body has fully recovered. If symptoms persist after 6 months, then you should see your doctor again. When you recover, your body will have learned to fight off a future hepatitis A infection. However, you can still get other kinds of hepatitis.

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) supports basic and clinical research into many digestive disorders, including hepatitis A. Researchers are studying new ways to prevent hepatitis A. Participants in clinical trials can play a more active role in their own health care, gain access to new research treatments before they are widely available, and help others by contributing to medical research. For information about current studies, visit www.ClinicalTrials.gov.

Publications produced by the Clearinghouse are carefully reviewed by both NIDDK scientists and outside experts. The NDDIC would like to thank the following individuals for providing scientific and editorial review or facilitating field-testing of the original version of this publication: Bruce Bacon, M.D. American Liver Foundation New York, NY Theo Heller, M.D. NIDDK, National Institutes of Health Bethesda, MD Luby Garza-Abijaoude, M.S., R.D., L.D. Texas Department of Health Austin, TX Thelma Thiel, R.N. Hepatitis Foundation International Cedar Grove, NJ

<ul> <li> Readers Comments 51 </li> <li> Share Your Story </li> </ul> An aneurysm is an area of a localized widening (dilation) of a blood vessel. The word "aneurysm" is borrowed from the Greek "aneurysma" meaning "a widening." An aortic aneurysm involves the aorta, the major artery that leaves the heart to supply blood to the body. An aortic aneurysm is a dilation or bulging of the aorta.Aortic aneurysms can develop anywhere along the length of the aorta but the majority are located in the abdominal aorta. Most of these abdominal aneurysms are located below the level of the renal arteries, the vessels that provide blood to the kidneys. Abdominal aortic aneurysms can extend into the iliac arteries.The inside walls of aneurysms are often lined with a blood clot that forms because there is stagnant blood. The wall of an aneurysm is layered, like a piece of plywood.What are the thoracic and abdominal aorta?The aorta is the large artery that exits the heart and delivers blood to the body. It begins at the aortic valve that separates the left ventricle of the heart from the aorta and prevents blood from leaking back into the heart after a contraction, when the heart pumps blood. The various sections of the aorta are named based upon the relation to the heart and the location in the body. Thus, the beginning of the aorta is referred to as the ascending aorta, followed by the arch of the aorta, then the descending aorta. The portion of the aorta that is located in the chest (thorax) is referred to as the thoracic aorta, while the abdominal aorta is located in the abdomen. The abdominal aorta extends from the diaphragm to the mid-abdomen where it splits into the iliac arteries that supply the legs with blood.

The risk factors for aortic aneurysm are the same as those for atherosclerotic heart disease, stroke, and peripheral artery disease and include:<ul><li>Cigarette smoking: This not only increases the risk of developing an abdominal aortic aneurysm, but also increases the risk of aneurysm rupture. Aortic rupture is a life-threatening event where blood escapes the aorta and the patient can quickly bleed to death.</li><li>High blood pressure</li><li>Elevated blood cholesterol levels</li><li>Diabetes mellitus</li></ul>

Abdominal aortic aneurysms gradually expand over time. The larger the aneurysm, the greater the risk of rupture and death. Small aneurysms can be observed and followed with repeated ultrasounds or other imaging.Guidelines for following an aneurysm are as follows:<ul><li>A normal aorta measures up to 1.7 cm in a male and 1.5 cm in a female.</li><li>Aneurysms that are found incidentally or by accident that are less than 3.0 cm do not need to be re-evaluated or followed.</li><li>Aneurysms measuring 3.0 to 4.0 cm should be rechecked by ultrasound every year to monitor for potential enlargement and dilation.</li><li>Aneurysms measuring 4.0 to 4.5 cm should be monitored every 6 months by ultrasound.</li><li>Aneurysms measuring greater than 4.5 cm should be evaluated by a surgeon for potential repair.</li></ul>

Once an aneurysm is detected, the goal is to try to prevent it from enlarging. Life-long control of risk factors is a must and includes the following:<ul><li>Stopping cigarette smoking.</li><li>Controlling high blood pressure: Beta blocker medications may be used to control both blood pressure and to decrease the pressure within the aneurysm.</li><li>Controlling blood cholesterol.</li><li>Keeping diabetes under control.</li><li>Routine monitoring of the size of the aneurysm:<ul><li>A normal aorta measures up to 1.7 cm in a male and 1.5 cm in a female.</li><li>Aneurysms that are found incidentally or by accident that are less than 3.0 cm do not need to be re-evaluated or followed.</li><li>Aneurysms measuring 3.0 to 4.0 cm should be rechecked by ultrasound every year to monitor for potential enlargement and dilation.</li><li>Aneurysms measuring 4.0 to 4.5 cm should be monitored every 6 months by ultrasound.</li><li>Aneurysms measuring greater than 4.5 cm should be evaluated by a surgeon for potential repair.</li></ul></li></ul>

*Facts medically reviewed by Charles P. Patrick, MD, PhD<ul><li>Alpha1 antitrypsin deficiency (AATD, antitrypsin deficiency, or alpha 1 antitrypsin deficiency) is a disorder (disease) that causes the alpha-1 antitrypsin (AAT) protein to be reduced or missing from the blood. This protein is necessary for healthy lungs, and the body uses it to protect the lungs from damage. If a person has low or no levels of AAT their lungs may be damaged.</li><li>Statistically, the disorder affects about one in 1500 to 3500 individuals with European ancestry. It is uncommon in Asians.</li><li>The signs and symptoms most people experience with this deficiency are:<ul><li>Chronic cough</li><li>Emphysema</li><li>COPD</li><li>Liver failure</li><li>Hepatitis</li><li>Hepatomegaly (enlarged liver)</li><li>Jaundice</li><li>Cirrhosis</li></ul></li><li>Mutations in the gene termed SERPNA1 cause alpha –1 antitrypsin deficiency.</li><li>A patient with lung or liver disease like COPD (chronic obstructive pulmonary disease) with no obvious cause maybe AATD deficient.</li><li>Doctors can confirm the diagnosis of this deficiency with blood tests or liver biopsy.</li><li>How doctors treat AATD depends on the patient’s signs and symptoms. Examples of treatments include:</li><li>Bronchodilators and inhaled steroids can help lung problems.</li><li>Intravenous use of purified human ATT (Prolastin) raise the level of ATT in the blood and lungs (augmentation therapy) - end stage lung and liver disease may need transplantation of these organs as a definitive treatment.</li><li>Management of AATD involves pulmonary function tests, liver function monitoring and yearly vaccinations against influenza. Moreover, doctors recommend that patient’s with the deficiency be vaccinated against hepatitis A and B, and pneumococcus.<ul><li>Stop smoking or reduce exposure to secondhand smoke.</li><li>Reduce exposure to environmental pollutants.</li></ul></li><li>The prognosis for someone with this problem is quite variable, and is related to the development and progression of severity of the symptoms. However, many people have a somewhat shortened lifespan. If the symptoms are severe, the prognosis can be very poor.</li><li>Medical professionals refer to alpha-1 antitrypsin deficiency.<ul><li>AAT</li><li>AATD</li><li>Alpha-1 proteinase inhibitor</li><li>Alpha-1 related emphysema</li><li>Genetic emphysema</li><li>Hereditary pulmonary emphysema</li><li>Inherited emphysema</li></ul></li></ul>

<ul> <li> Readers Comments 11 </li> <li> Share Your Story </li> </ul> The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies.Signs and Symptoms of Alpha-1 Antitrypsin DeficiencySigns and SymptomsApproximate number of patients (when available)EmphysemaVery frequent (present in 80%-90% of cases)Hepatic failure (liver failure)Very frequent (present in 80%-90% of cases)Hepatitis (liver inflammation or infection)Frequent (present in 30%-79% of cases)An abnormally enlarged liver (hepatomegaly)Frequent (present in 30%-79% of cases)Jaundice (signs of a liver problem)Frequent (present in 30%-79% of cases)Cirrhosis (a complication of liver disease)Occasional (present in 5%-29% of cases)Autosomal recessive inheritanceCOPD (chronic obstructive pulmonary disease)Shortness of breath (Dyspnea)Elevated hepatic transaminasesLiver cancer (hepatocellular carcinoma)

<ul> <li> Readers Comments 2 </li> <li> Share Your Story </li> </ul> Mutations in the SERPINA1 gene cause alpha-1 antitrypsin deficiency.The SERPINA1 gene provides instructions for making a protein called alpha-1 antitrypsin. This protein protects the body from being damaged by a powerful enzyme called neutrophil elastase. Neutrophil elastase is released from white blood cells to fight infection, but it can attack normal tissues (such as lung tissue) if not carefully controlled by alpha-1 antitrypsin. Mutations in the SERPINA1 gene can lead to a shortage (deficiency) of alpha-1 antitrypsin protein or an abnormal form of the protein that cannot control neutrophil elastase. Uncontrolled, neutrophil elastase destroys alveoli, which can lead to emphysema. The abnormal form of alpha-1 antitrypsin can also accumulate in the liver and may damage this organ.

Treatment of alpha-1 antitrypsin deficiency (AATD) depends on the symptoms and severity in each person. COPD and other related lung diseases are typically treated with standard therapy.[3][4] Bronchodilators and inhaled steroids can help open the airways and make breathing easier.[4]Intravenous augmentation therapy (regular infusion of purified, human AAT to increase AAT concentrations) has been recommended for people with established fixed airflow obstruction (determined by a specific lung function test).[3] This therapy raises the level of the AAT protein in the blood and lungs.[4]Lung transplantation may be an appropriate option for people with end-stage lung disease. Liver transplantation is the definitive treatment for advanced liver disease.[3]When present, panniculitis may resolve on its own or after dapsone or doxycycline therapy. When this therapy does not help, it has responded to intravenous augmentation therapy in higher than usual doses.[3]All people with severe AATD should have pulmonary function tests every 6 to 12 months. Those with ATT serum concentrations 10% to 20% of normal should have periodic evaluation of liver function to detect liver disease. People with established liver disease should have periodic ultrasounds of the liver to monitor for fibrotic changes and liver cancer (hepatocellular carcinoma).[3]Yearly vaccinations against influenza and pneumococcus are recommended to lessen the progression of lung disease. Vaccination against hepatitis A and B is recommended to lessen the risk of liver disease. People with AATD should avoid smoking and occupations with exposure to environmental pollutants.[3]Parents, older and younger siblings, and children of a person with severe AATD should be evaluated to identify as early as possible those who would benefit from treatment and preventive measures.[3]Management guidelines<ul><li>GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.</li><li>Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition</li></ul>

The prognosis of a genetic condition includes its likely course, duration, and outcome. When health professionals refer to the prognosis of a disease, they may also mean the chance of recovery; however, most genetic conditions are life-long and are managed rather than cured.Disease prognosis has multiple aspects, including:<ul><li>How long a person with the disorder is likely to live (life expectancy)</li><li>Whether the signs and symptoms worsen (and how quickly) or are stable over time</li><li>Quality of life, such as independence in daily activities</li><li>Potential for complications and associated health</li></ul>The prognosis of a genetic condition depends on many factors, including the specific diagnosis and an individual's particular signs and symptoms. Sometimes the associated genetic change, if known, can also give clues to the prognosis. Additionally, the course and outcome of a condition depends on the availability and effectiveness of treatment and management approaches. The prognosis of very rare diseases can be difficult to predict because so few affected individuals have been identified. Prognosis may also be difficult or impossible to establish if a person's diagnosis is unknown.The prognoses of genetic disorders vary widely, often even among people with the same condition. Some genetic disorders cause physical and developmental problems that are so severe they are incompatible with life. These conditions may cause a miscarriage of an affected embryo or fetus, or an affected infant may be stillborn or die shortly after birth. People with less severe genetic conditions may live into childhood or adulthood but have a shortened lifespan due to health problems related to their disorder. Genetic conditions with a milder course may be associated with a normal lifespan and few related health issues.The prognosis of a disease is based on probability, which means that it is likely but not certain that the disorder will follow a particular course. Your healthcare provider is the best resource for information about the prognosis of your specific genetic condition. He or she can assess your medical history and signs and symptoms to give you the most accurate estimate of your prognosis.

*Facts medically reviewed by Charles P. Patrick, MD, PhD<ul><li>Alpha1 antitrypsin deficiency (AATD, antitrypsin deficiency, or alpha 1 antitrypsin deficiency) is a disorder (disease) that causes the alpha-1 antitrypsin (AAT) protein to be reduced or missing from the blood. This protein is necessary for healthy lungs, and the body uses it to protect the lungs from damage. If a person has low or no levels of AAT their lungs may be damaged.</li><li>Statistically, the disorder affects about one in 1500 to 3500 individuals with European ancestry. It is uncommon in Asians.</li><li>The signs and symptoms most people experience with this deficiency are:<ul><li>Chronic cough</li><li>Emphysema</li><li>COPD</li><li>Liver failure</li><li>Hepatitis</li><li>Hepatomegaly (enlarged liver)</li><li>Jaundice</li><li>Cirrhosis</li></ul></li><li>Mutations in the gene termed SERPNA1 cause alpha –1 antitrypsin deficiency.</li><li>A patient with lung or liver disease like COPD (chronic obstructive pulmonary disease) with no obvious cause maybe AATD deficient.</li><li>Doctors can confirm the diagnosis of this deficiency with blood tests or liver biopsy.</li><li>How doctors treat AATD depends on the patient’s signs and symptoms. Examples of treatments include:</li><li>Bronchodilators and inhaled steroids can help lung problems.</li><li>Intravenous use of purified human ATT (Prolastin) raise the level of ATT in the blood and lungs (augmentation therapy) - end stage lung and liver disease may need transplantation of these organs as a definitive treatment.</li><li>Management of AATD involves pulmonary function tests, liver function monitoring and yearly vaccinations against influenza. Moreover, doctors recommend that patient’s with the deficiency be vaccinated against hepatitis A and B, and pneumococcus.<ul><li>Stop smoking or reduce exposure to secondhand smoke.</li><li>Reduce exposure to environmental pollutants.</li></ul></li><li>The prognosis for someone with this problem is quite variable, and is related to the development and progression of severity of the symptoms. However, many people have a somewhat shortened lifespan. If the symptoms are severe, the prognosis can be very poor.</li><li>Medical professionals refer to alpha-1 antitrypsin deficiency.<ul><li>AAT</li><li>AATD</li><li>Alpha-1 proteinase inhibitor</li><li>Alpha-1 related emphysema</li><li>Genetic emphysema</li><li>Hereditary pulmonary emphysema</li><li>Inherited emphysema</li></ul></li></ul>