Hereditary Angioedema

Hereditary angioedema (HAE) is a genetic condition and there is no cure. A person will not outgrow the disorder. People with HAE will receive periodic evaluations (screenings) to track the progress of the disorder. Although there is no cure, people who receive appropriate treatment of episodes and have developed an individual treatment and care plan with their doctors have a favorable prognosis and can have a normal or near-normal life expectancy. However, risks associated with the disorder, such as a life-threatening episode, will always exist.

In a family with hereditary angioedema (HAE), tests can be done to see whether other family members have the disorder. If one parent is affected, then all children and siblings of that parent should be tested. This involves running blood tests. The first test will be to detect levels of a protein called C4 complement. Another blood test is performed to detect low levels of C1 inhibitor. For patients with HAE type I (85% of patients), the C4 level and C1 inhibitor levels are typically low. For patients with HAE type II (15% of patients) the C4 level is typically low, however, the C1 inhibitor level may be normal or high, but it is not functioning correctly.

If the specific changes in the SERPING1 gene are known then molecular genetic testing can be used. These tests look for changes in the SERPING1 gene. However, such testing is usually not necessary.

Support groups can put you in contact with other people or families that have hereditary angioedema (HAE). Support groups for HAE include the U.S. Hereditary Angioedema Association, HAE Canada, and HAEi – International Patient Organization for C1 Inhibitor Deficiencies.

There are also online communities for rare disorders such as RareConnect, RareShare, or Inspire, which allow individuals and parents to share experiences and advice about dealing with rare disorders.

The medical cost of hereditary angioedema (HAE) can be significant. Some families lack the resources necessary to provide for a chronically ill family member. There are several organizations that provide financial assistance.

Support groups for HAE provide advice, guidance, and resources for handling the financial costs associated with a diagnosis of HAE. These support groups include the U.S. Hereditary Angioedema Association, HAE Canada, and HAEi – International Patient Organization for C1 Inhibitor Deficiencies.

The National Organization for Rare Disorders (NORD) has links to organizations that can provide financial assistance.

The National Human Genome Research Institute has extensive information on finding financial aid for medical treatment and services.

Hereditary angioedema is a variable disorder. Therefore, the symptoms that an individual experiences and the age of onset can be very different from person to person. Experiencing an episode prior to age 2 is rare. Roughly 40% of patients will experience an episode by age 5 and 75% will experience an episode by age 15. The frequency of episodes usually increases after puberty.

A doctor may suspect a diagnosis of hereditary angioedema (HAE) because of certain symptoms. HAE may be suspected because of recurrent episodes of severe swelling that are not accompanied by a rash or itching and do not respond to treatment with antihistamines or corticosteroids the way an allergic reaction does. Because of the rarity of HAE, a diagnosis is often delayed. Some estimates suggest that many individuals have a delay in diagnosis of about 10 years. Initial episodes may be mistaken for an allergic reaction.

If doctors suspect someone of having HAE, they will perform blood tests to measure C4 and C1 inhibitor. The first test will be to detect levels of a protein called C4 complement. Another blood test is performed to detect low levels of C1 inhibitor. For patients with HAE type I (85% of patients), the C4 level and C1 inhibitor levels are typically low. For patients with HAE type II (15% of patients), the C4 level is typically low; however, the C1 inhibitor level may be normal or high, but it is not functioning correctly.

A diagnosis can be confirmed by molecular genetic testing. These tests involve studying the SERPING1 gene for changes that cause the disorder. However, this type of test is not always necessary to make a diagnosis.

Hereditary angioedema (HAE) can be very different in one person compared to another. Therefore, the severity and frequency of episodes can vary dramatically. In addition, it is difficult to make predictions about how the disease will progress for an individual. Advances in treating acute episodes have greatly improved the outlook of this disorder in the last several years.

Overall, the prognosis for people with HAE who have access to treatments and have developed an individualized treatment plan with their doctors and medical team is very good and they can have fulfilling lives with a normal lifespan. The risk of throat and airway swelling, however, does remain throughout the lifespan and can cause life-threatening respiratory arrest. About 50% of people with HAE will have at least one episode involving life threatening throat and airway swelling. Talk to your doctor and entire medical team about you or your child’s diagnosis and individual prognosis.

Hereditary angioedema or HAE is a genetic disorder, in which affected individuals have a problem in a specific gene. People have about 20,000-25,000 genes in their bodies. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. Because of a change in the SERPING1 gene, people with HAE are deficient in a protein called C1 inhibitor (HAE type 1), or have normal or elevated levels of this protein, but the protein does not function properly (HAE type II). Because they lack enough functional levels of this protein, people with HAE have repeated episodes of inflammation and swelling. This swelling is like the swelling seen in an allergic reaction. However, unlike an allergic reaction, there is usually no skin rash or itching. Swelling can occur in the face, hands, feet, eyelids, lips, tongue, and the mucous membrane lining the gastrointestinal tract. Less often, swelling can also affect the throat or upper airways; these episodes can sometimes cause life-threatening complications. The specific symptoms depend upon what areas of the body are affected during an episode. The disorder can affect people very differently. Some people may only have very few episodes or symptoms, while others have repeated, severe episodes of swelling. Episodes usually last 2-5 days and go away on their own without treatment. However, there are several drugs available to treat rapid, severe episodes of HAE, and some people may need preventive treatment. Specific treatments for people with HAE differ. People with HAE should work with their physicians and entire medical team to develop an individualized treatment plan that is best for them.

Most people with hereditary angioedema (HAE) have a change in the SERPING1 gene. People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA. Genes are segments of DNA found on chromosomes that are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. Genes produce specific proteins that the body needs to grow and work properly. When there is an unexpected change in a gene, the protein that the gene produces may be absent, not work properly, or be overproduced.

Because of a change in the SERPING1 gene, people with HAE are deficient in a protein called C1 inhibitor (HAE type 1), or have normal or elevated levels of this protein, but the protein does not function properly (HAE type II). Because they lack enough functional levels of this protein, people with HAE have repeated episodes of inflammation and swelling.

To find a medical professional nearby who can discuss information about gene changes in HAE, a listing of medical geneticists can be found at the American College of Medical Geneticists website. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Rare diseases that affect multiple organ systems like hereditary angioedema (HAE), can benefit from a multidisciplinary approach. This approach involves healthcare professionals with specialized skills and expertise. The specialized professionals work together to make treatment recommendations and to provide quality care for individuals and families. Depending upon the specific symptoms, in an individual multidisciplinary team may require a specialist who can assess and treat problems of the immune system (immunologist); an ear, nose and throat specialist (otolaryngologist) who can assess and treat disorders of the ear, nose and throat; a specialist in digestive disorders (gastroenterologist) who can treat problems of the gastrointestinal system; a genetic counselor who can help people understand the disease and the implications for the person and other family members; a child behavior specialist; and a metabolic disease specialist.

Talk to your doctor about the best specialists in your area to follow an individual with hereditary angioedema.

There are several different things that can trigger an episode of swelling in people with hereditary angioedema (HAE). Common triggers are surgery, dental procedures, trauma, mental or physical stress, and infection. Women can have an episode triggered by taking oral contraceptives, pregnancy, or menstruation. Sometimes, no trigger can be identified. The triggers in one person may not cause an episode in another person.

When infants and children have a chronic disorder like hereditary angioedema (HAE), it can demand a lot of time and focus from parents. As with similar disorders, it is easy for healthy siblings to feel as if they have been pushed aside. Although studies have shown that siblings of children with chronic illness tend to develop strong levels of compassion and empathy, these studies have also shown that siblings can develop feelings of jealousy, anger, and high levels of anxiety. Parents can work with siblings by having clearly defined roles and responsibilities within the family structure. Parents are encouraged to make time for activities, especially for healthy siblings, and to talk with and encourage healthy siblings to address their concerns and feelings. Some children may benefit from support outside of the immediate family including therapists or doctors. The Sibling Support Project is a nonprofit organization that serves the concerns and needs of siblings of people with special health, developmental, and mental health needs.

Early signs of an episode of hereditary angioedema (HAE) affecting the throat can include changes in voice, difficulty swallowing, the feeling of the throat tightening or the feeling of a lump in the throat. This may be followed by labored or difficult breathing. These episodes can go away on their own without any treatment. However, they can potentially cause life-threatening breathing problems and should be treated as a medical emergency. Individuals with HAE should have a plan, developed with their doctors, on how to treat these episodes and where to go to find appropriate medical care.

People with hereditary angioedema (HAE) experience recurrent episodes of severe swelling (angioedema) that, if untreated, usually last between 2-5 days. These episodes usually start in childhood or adolescence. They often become more frequent after puberty. The frequency and severity of these episodes can be very different among people with the disorder, even among people in the same family. Some people have episodes weekly, while others may only have one or two a year.

The most common areas affected are the skin, particularly the hands and feet. The lips, tongue, and genitals can be affected. The gastrointestinal tract and the airways including the throat can also be affected and cause disabling symptoms. The symptoms that develop will depend on the part of the body affected. Often, the swelling will go away (subside) without lasting effects. However, there is a risk for severe, disabling or life-threatening complications.

If the gastrointestinal tract is involved, then there may be abdominal pain, nausea, vomiting, diarrhea, and abdominal swelling. Sometimes, people may have rapid, severe (acute) pain in the abdomen, which can be debilitating and often mistaken for other conditions. Sometimes, people undergo unnecessary surgery to try and determine the cause of gastrointestinal problems because HAE is not considered for the diagnosis. Some people can be bedridden for a few days during and just after a painful episode. In severe instances, people may faint because of a significant loss of blood.

If the throat or respiratory tract is involved, people may have difficulty swallowing or speaking, and in severe instances the airways may be blocked and people can die from a lack of oxygen (asphyxiation). An episode affecting the throat or upper airways is a medical emergency and requires prompt treatment. People with HAE should be educated to identify the signs and symptoms of an episode that involves these areas. Such signs include tightening in the throat, the feeling of a lump in the throat, or difficulty speaking or swallowing.

Sometimes, people with HAE will develop nonspecific symptoms just before an episode happens. This can be a feeling of being unwell, muscle pain, a rash, fatigue or nausea. Sometimes, these symptoms occur and an episode does not follow.

To find a medical genetics clinic near you use the Find a Medical Geneticist tool on the American College of Medical Genetics and Genomics website. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

The frequency and severity of episodes of swelling in hereditary angioedema (HAE) can be very different among people. Some people may have one episode per week, while others may have one episode per year. The severity is unpredictable even among people in the same family. The frequency may also change for people at different times during their lives.

After an initial diagnosis of hereditary angioedema (HAE), your doctor will take a comprehensive medical history. People with HAE should receive information about their disorder, work with doctors to develop a plan for acute episodes and an overall treatment plan, and work to identify and avoid triggers. Doctors may recommend testing family members to see whether they also have the disorder.

The best way to obtain the most accurate, current, clear, and comprehensive information is to be seen at a center or clinic that specializes in hereditary angioedema (HAE). There is a center in the United States that specializes in the treatment of patients with HAE: the Angioedema Center at UC San Diego. This center-of-excellence offers comprehensive care for patients with angioedema, state-of-the-art diagnostic tests and techniques, the latest available therapeutic modalities, a full range of patient support programs, and cutting-edge translational research in angioedema. The Angioedema Center, in partnership with the US Hereditary Angioedema Association, aspires to improve the lives of angioedema patients throughout the world.

Support groups may have information on doctors who are experienced in treating hereditary angioedema. These support groups include the U.S. Hereditary Angioedema Association, HAE Canada, and HAEi – International Patient Organization for C1 Inhibitor Deficiencies.

Estrogen-containing oral contraceptives and hormone replacement therapy can trigger an episode and also increase the frequency of episodes in hereditary angioedema (HAE). A group of medications, called angiotensin-converting enzyme (ACE) inhibitors, which are used to treat a variety of conditions including high blood pressure, can also increase the frequency or trigger an HAE episode. People with HAE should talk to their physicians before beginning any new medication to see whether it is safe for people with HAE.

Hereditary angioedema is not one of the disorders that is screened for at birth. The disorder rarely causes symptoms in infancy. If a baby appears to have health problems that could be caused by HAE, the easiest way to begin testing for the disorder is to discuss it with a pediatrician or primary care doctor. Referral to a metabolic genetic specialist may be necessary. Testing information in your area can also be obtained through a genetic counselor. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

There are currently many clinical trials related to hereditary angioedema listed on clinicaltrials.gov, a government website that provides regularly updated information about federally and privately supported clinical trials. This may not be an exhaustive list of current research. Current studies are looking at ways to screen for certain symptoms of HAE, various new treatments such as new drug therapies, further studies into approved therapies, studies on how to best treat acute episodes of swelling, and studies to assess treatment in children.

For the most up-to-date list, contact clinical trials.gov and search for hereditary angioedema.

Although there is no cure for hereditary angioedema (HAE), there are effective treatments. Every person with HAE needs a comprehensive treatment plan, especially a plan that details how to handle acute episodes. This plan should be developed with a physician who has experience in treating and HAE and should include where and how a person will receive treatment, especially when having an acute episode.

People with HAE are encouraged to carry a wallet card or ID bracelet that explains their condition. They should carry written instructions in case they are in an emergency room setting since most physicians will be unfamiliar with this disorder. Many people with HAE have learned how to treat themselves when undergoing an acute episode. This is called self-administration. People should also understand what may trigger an episode so they can try to avoid such triggers. All people with HAE should be taught to identify the early signs or symptoms of an episode affecting the throat or upper airways, which is a medical emergency. Anyone experiencing an episode involving the throat should seek immediate medical care, even if they have self-administered treatment.

The treatment for HAE is highly individualized. The U.S. Food and Drug Administration has approved several different medications for the treatment of HAE. The Hereditary Angioedema Association has information on these medications. Most of these medications act by replacing the deficient or dysfunctional C1 inhibitor protein, or by limiting the production of bradykinin, the hormone that is overproduced in HAE.

Some people may need preventative therapy (prophylaxis). Treatment plans for affected individuals may focus on long-term preventative treatment and short-term preventative treatment. Long-term therapy is given to individuals with frequent or severe episodes and can include synthetic versions of androgens to help increase the level of C1 inhibitor and antifibrinolytics, which are medications that slow the breakdown of clotting factors in the blood. Patients may also be given C1 inhibitor replacement therapy to replace the deficient or dysfunctional C1 inhibitor that is present in affected individuals. Short-term preventative treatment may be considered for patients who will be exposed to known episodic triggers.

Women with hereditary angioedema (HAE) can have children. Sometimes, the frequency and severity of HAE episodes increase during pregnancy and other times there is no change or increase in episodes. This remains true for individual women who have multiple pregnancies. Generally, abdominal episodes tend to occur more often during pregnancy.

Women who have HAE and are planning on having children should discuss a treatment plan with their HAE-treating physicians, their obstetricians, and entire medical team. A plan should be developed on whether preventive treatment is necessary, how to treat an acute episode if it occurs during the pregnancy, and how to monitor and treat the mother after the pregnancy is over.

HAE is a genetic disorder. If one parent has a gene change in the SERPING1 gene that causes the disorder, then there is a 50% chance for each pregnancy that the child will have HAE. Parents should talk to a genetic counselor about the genetics of HAE before becoming pregnant.

Hereditary angioedema (HAE) is a genetic disorder. It is most commonly caused by changes to the SERPING1 gene (HAE types I and II). These genes produce a protein called C1 inhibitor. Some people may think of HAE as a blood disorder because the protein, C1inhibitor, produced by the SERPING1 gene is found in the blood. However, C1 inhibitor is part of the body’s immune system, so HAE is more correctly thought of as an immunologic disorder and not a blood disorder.

Some people who have a change in the SERPING1 gene that causes hereditary angioedema (HAE) type I or II will not develop symptoms. Some people may go through their entire life without knowing they have the disorder. Other times, people find out they have HAE because they are screened for the disorder because a family member has it, but they do not have any symptoms. It is possible, in these people, that symptoms will develop at some point. Penetrance is a term that refers to the proportion of people with a particular genetic variant (or gene mutation) who exhibit signs and symptoms of a genetic disorder. "Complete penetrance" means that all people with gene changes/mutations will have clinical features of the condition. "Reduced penetrance" means that not everyone who has a gene change/mutation will have clinical features. There can be many factors that determine if someone is more likely to show clinical features than others; however, sometimes the cause for this is unknown.

In general, the symptoms and severity of HAE will differ greatly among people. This is even true of people in the same family or people who have the same change in the SERPING1 gene. Most genetic conditions, including hereditary angioedema, have symptoms that differ among affected individuals. Variable expressivity refers to the range of symptoms that can occur in different people with the same genetic condition.

We each get two copies of most of our genes from our parents. One copy comes from our mother and the other copy comes from our father. Hereditary angioedema (HAE) is caused when the SERPING1 gene is altered (mutated). In HAE, only one parent must pass along a nonworking copy of the altered gene to cause the disorder. Because of this, HAE is inherited in what is called an autosomal dominant pattern. This means a person only needs one altered gene to have the disorder. In most families with HAE, one parent will have an alteration in one of these genes, which causes their disease. So, each of their children will have a 50% chance of inheriting that mutation and developing the disease.

About 25% of the time, a child will develop HAE and be the first person in the family with the disorder. This occurs because of a de novo mutation, which means that the altered gene occurs randomly, most likely after fertilization. The child who carries the altered gene will pass on the alteration in an autosomal dominant manner. In families with a child with a de novo mutation, the likelihood of having another child with HAE is extremely low.

To find a medical genetics clinic near you use the Find a Medical Geneticist tool on the American College of Medical Genetics and Genomics website. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Hereditary angioedema (HAE) is inherited in an autosomal dominant manner. This is one way a disorder or trait can be passed down through a family. The first word, "autosomal," means on a chromosome that both males and females carry. Therefore, HAE can affect either gender. The second word, "dominant," means a gene change in one copy of an HAE gene is enough to develop the disease. We have two copies of every gene – one from our mother and one from our father. In dominant conditions, only one gene needs to have the problem for the condition to be expressed. This means that if a parent carries an altered SERPING1 gene, they have a 50% chance to pass the affected gene to each of their offspring, regardless of gender. This also means that there is a 50% chance that an affected parent would not pass this on to their children.

About 25% of the time, there is no previous history of HAE in the family. The altered gene occurs randomly, most likely after fertilization. This is called a de novo mutation. The altered gene in the child will be passed on as an autosomal dominant trait. In families with a child with a de novo mutation, the likelihood of having another child with the disorder is extremely low.

If you have a family member with HAE and you would like to know if you are a carrier or learn more about the genetics of the disorder, finding a genetic counselor in your area may be helpful. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

Most people with hereditary angioedema (HAE) have a change in the SERPING1 gene. People have about 20,000-25,000 genes in their bodies. Our genes contain our body’s genetic information, called DNA; genes are segments of DNA found on chromosomes. Genes are inherited from our parents and passed on to our children. Genes are like our body’s instruction manual – they control the growth, development and normal function of the body. Genes produce specific proteins that the body needs to grow and work properly. When there is an unexpected change in a gene, the protein that the gene produces may be absent, not work properly or be overproduced.

Because of a change in the SERPING1 gene, people with HAE are deficient in a protein called C1 inhibitor (HAE type 1), or have normal or elevated levels of this protein, but the protein does not function properly (HAE type II). Because they lack enough functional levels of this protein, people with HAE have repeated episodes of inflammation and swelling.

C1 inhibitor has several functions in the body including blocking the activity of certain proteins involved in inflammation. It is part of the body’s immune system. The lack of functional C1 inhibitor eventually leads to an overproduction of a peptide hormone called bradykinin. Bradykinin has several roles in the body including regulating the widening (dilation) and permeability of blood vessels. Increased permeability means that fluids can leak out of blood vessels; the buildup of these fluids contributes to the swelling seen in HAE.

A doctor may suspect a diagnosis of hereditary angioedema (HAE) because of certain symptoms. HAE may be suspected because of recurrent episodes of severe swelling that are not accompanied by a rash or itching. Because of the rarity of HAE, a diagnosis is often delayed. Some estimates suggest that many individuals have a delay in diagnosis of about ten years. Initial episodes may be mistaken for an allergic reaction.

If doctors suspect someone of having HAE, they will perform blood tests to measure C4 and C1 inhibitor. The first test will be to detect levels of a protein called C4 complement. Another blood test is performed to detect low levels of C1 inhibitor. For patients with HAE type I (85% of patients), the C4 level and C1 inhibitor levels are typically low. For patients with HAE type II (15% of patients), the C4 level is typically low; however, the C1 inhibitor level may be normal or high, but it is not functioning correctly.

A doctor can recommend genetic testing to confirm a diagnosis of HAE. These tests involve studying the SERPING1 gene for changes (mutations).

If you believe that you or someone in your family has HAE, you can request or seek out a referral to a genetics clinic that may be more familiar with these disorders. The Hereditary Angioedema Association provides information on how to find healthcare professionals or medical centers with experience in with HAE. In addition, to find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

To learn about ongoing clinical research into hereditary angioedema (HAE) ask a physician who specializes in the disorder. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Genetics and Genomics website. Genetic counselors can be found on the National Society of Genetic Counselors website.

Ongoing studies for HAE can also be found on clinicaltrials.gov, a service of the U.S. National Institutes of Health. In Europe, the EU Clinical Trial Register performs a similar service.

Support groups also have information about ongoing clinical trials as well as information and advice about participating in clinical trials. Support groups for HAE include the Hereditary Angioedema Association and HAE Canada. HAEi – International Patient Organization for C1 Inhibitor Deficiencies, is an international umbrella organization for the world’s Hereditary Angioedema (HAE) patient groups..

The best way to obtain the most accurate, current, clear, and comprehensive information is to be seen at a center or clinic that specializes in hereditary angioedema (HAE). There is a center in the United States that specializes in the treatment of patients with HAE: the Angioedema Center at UC San Diego. This center-of-excellence offers comprehensive care for patients with angioedema, state-of-the-art diagnostic tests and techniques, the latest available therapeutic modalities, a full range of patient support programs, and cutting-edge translational research in angioedema. The Angioedema Center, in partnership with the US Hereditary Angioedema Association, aspires to improve the lives of angioedema patients throughout the world.

Support groups may have information on doctors who are experienced in treating hereditary angioedema. These support groups include the U.S. Hereditary Angioedema Association, HAE Canada, and HAEi – International Patient Organization for C1 Inhibitor Deficiencies.

Children with hereditary angioedema should have an individualized treatment plan that is put together with physicians who have experience treating this disorder. In the United States, there is an HAE treatment center in San Diego. These specialists can work with a patient to develop a treatment plan and help educate local doctors about HAE. When children grow up, and their care transitions to a new set of doctors, some challenges may arise. Transitioning care to a new medical team is less challenging with good communication among the specialists and with the patient. While it may also be challenging as a child becomes an adult and must bear a greater responsibility for their health, many hospitals and specialty clinics have programs to help children with chronic diseases transition to adult care services.

Children with hereditary angioedema (HAE) can attend regular school. Children should have an individualized treatment plan devised by their doctors. They should also have access to medications in case of an acute episode of swelling. Because of some issues, they may need special accommodations in school. They may qualify for an individual education plan (IEP) or a 504 plan. A 504 plan ensures that students with disabilities can fully participate in school and have access to the same educational opportunities as all children. Parents are encouraged to provide a school with a packet of information on HAE and to work with school officials including teachers, nurses, psychologists, the principal, and other professionals.

The U.S. Department of Education has information on individualized education plans and 504 plans. The Hereditary Angioedema Association has information on how to advocate for a child with HAE, 504 plans, and how to address issues in school. Global Genes, a rare disease advocacy organization, has a RARE Toolkit that advises parents on advocating for their children at their school.

Hereditary angioedema (HAE) is a rare disorder. Rare disorders often go unrecognized or misdiagnosed and the incidence and prevalence of individual rare disorders is often unclear or unknown. Prevalence is the measurement of all individuals affected by the disease at a particular time. Incidence is the number of new people with a disorder or newly diagnosed. Most estimates suggest that HAE affects 1 in 50,000 to 100,000 people in the general population. Both men and women are affected by this disorder and it occurs in all racial and ethnic groups.

Generally, the frequency of episodes in hereditary angioedema increases after puberty. For many people, a diagnosis of hereditary angioedema will not be made until after puberty.

Hereditary angioedema does not cause intellectual disability. The disorder is characterized by repeated episodes of inflammation and swelling. This swelling is similar to an allergic reaction, but usually does not cause a skin rash or itching. Swelling can occur in the face, hands, feet, eyelids, lips, tongue, and the mucous membrane lining the gastrointestinal tract. Swelling can also affect the throat or upper airways; these episodes can cause life-threatening complications.

Episodes of significant swelling in hereditary angioedema that affect the skin can be disfiguring. The face, arms, legs and genitals are often involved. However, this swelling is usually not dangerous and goes away without any lasting disability or disfigurement.

Hereditary angioedema (HAE) can significantly affect quality of life. The disorder can be effectively treated, but it is a lifelong condition. Episodes that affect the gastrointestinal tract can cause significant pain and cause people to be bedridden during and after the episode. If the throat or airways are affected, HAE can cause life-threatening complications. Fatigue and temporary disfigurement can also occur during episodes. HAE can disrupt a person’s daily activities and cause them to miss work. The frequency and severity of episodes can be very different among people, and the impact of the disorder on a person’s life can differ too. Support groups for HAE are important sources of support and information and help with managing the disorder. These groups include the Hereditary Angioedema Association and the Hereditary Angioedema Canada.

Hereditary angioedema can have an impact on an individual’s mental health. One study showed that people with hereditary angioedema (HAE) may be more likely to suffer from depression or anxiety. This may be due to dealing with the disorder itself, but also may be due to the effects of the disorder on the immune system. Children and adults with HAE should receive treatment that addresses their psychosocial well-being and mental health.

The medications commonly used to treat an allergic reaction, like corticosteroids or antihistamines, do not work for people with HAE. While the symptoms of hereditary angioedema are very similar to those diagnosed with an allergic reaction they are not treated with the same medication. It is important that HAE is promptly diagnosed so treatment with the therapies that do work for HAE can be started.

Hereditary angioedema (HAE) does not affect fertility. Both men and women can have children. For affected individuals, there is a 50% risk for each pregnancy that the child will also have HAE. Affected women need to have a specific HAE treatment plan for their pregnancy.

Because it is a genetic disorder, families affected by HAE should discuss family planning options with a genetic counselor before becoming pregnant. To find a genetic counselor in your area, use the National Society of Genetic Counselors Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

People with hereditary angioedema can travel, but they do need to plan and take some precautions. If you are bringing medication with you, make sure to keep it in your carry on bag. You can request a doctor’s note or prescription to take with you as well. People with HAE are advised to carry a wallet card or written information about their condition and appropriate medical treatment in case of an episode or emergency. Support groups often offer advice on how best to travel with a rare disorder. The Hereditary Angioedema Association provides travel information to people with HAE.

Women with HAE can breastfeed, but sometimes lactation can cause episodes to occur more often. Doctors recommend treating these episodes with C1 inhibitor concentrate rather than other options (i.e. androgens or tranexamic acid) because the effects of androgens or tranexamic acid on infants are unknown.

People with hereditary angioedema can sometimes tell that an episode is about to develop. There are several signs that can occur, including significant fatigue, discomfort near where the swelling will appear, and a skin condition called erythema marginatum, in which a pinkish or reddish rash appears on affected areas. Sometimes, muscle pains, flu-like symptoms or nausea and other gastrointestinal symptoms may occur. Symptoms that indicate the onset of a disorder or illness are called prodromal symptoms. In hereditary angioedema, they usually develop within 24 hours of an episode of swelling. However, sometimes these symptoms occur and are not followed by an episode.

Hereditary angioedema (HAE) is the most commonly used name for this disorder. Sometimes, people may refer to the disorder as C1 inhibitor deficiency. However, C1 inhibitor deficiency can refer to an acquired condition, while hereditary angioedema is a genetic disorder that is caused by changes to the SERPING1 gene. There are at least two other types of hereditary angioedema that have normal C1 inhibitor. Hereditary angioedema type III is caused by a gene change in the factor XII (FXII) gene. Some people have HAE with normal C1 inhibitor, but no identifiable gene change.

There are also some older names for HAE that sometimes appear in the medical literature including familial angioneurotic edema, hereditary angioneurotic edema, or hereditary non-histamine-induced angioedema.

There are support groups and organizations for hereditary angioedema (HAE) that provide support, information, advice, referrals to physicians and medical centers, and up-to-date information on research and treatments. Support groups for HAE include the U.S. Hereditary Angioedema Association and HAE Canada. HAEi – International Patient Organization for C1 Inhibitor Deficiencies, is an international umbrella organization for the world’s Hereditary Angioedema (HAE) patient groups.

There are several forms of hereditary angioedema (HAE). The main two forms, HAE type I and HAE type II are caused by changes in the SERPING1 gene. In type I, changes to this gene leads to a deficiency of a protein called C1 inhibitor. In type II, C1 inhibitor is not deficient (there may even be elevated levels), but the protein does not function properly.

There are other forms of HAE as well. One form was formerly called HAE type III, but is more often called HAE with normal C1 inhibitor. This form of HAE is caused by changes in the factor XII (FXII) gene. Other people have HAE despite normal C1 inhibitor, but the causative gene is not known.

Hereditary angioedema (HAE) can be mistaken for many other disorders or conditions. A diagnosis is often delayed by as much as ten years in some people. Allergic disorders and severe allergic reactions (anaphylaxis) are important to distinguish from HAE. These conditions cause swelling similar to that seen in HAE. However, the treatments for these more common conditions such as corticosteroids, antihistamines or epinephrine, do not work for HAE. Usually, allergic conditions have a rash, are itchy, or cause wheezing-symptoms that do not occur in HAE.

An episode of swelling in the gastrointestinal tract can be similar to an obstruction in the gastrointestinal tract. Some people with HAE may undergo unnecessary surgery because doctors may mistakenly think that an obstruction is present rather than HAE. Sometimes, people with HAE are misdiagnosed with appendicitis, stomach ulcers, or irritation or inflammation of the gastrointestinal system (gastroenteritis).

There are various autoimmune disorders that can mimic HAE. An autoimmune disorder is one in which the body’s immune system mistakenly attacks healthy tissue. Lupus is an example of an autoimmune disorder in which swelling may occur. Others include Sjogren syndrome, dermatomyositis or polymyositis.

Angioedema can also be acquired, meaning that the condition is not genetic. Acquired angioedema can occur because of the use of certain drugs or because of a type of disorder known as a lymphoproliferative disorder. Lymphoproliferative disorders are a group of disorders where white blood cells called lymphocytes grow out of control. Sometimes, a person with a lymphoproliferative disorder is deficient in the C1 inhibitor. This is caused by the underlying disease and is not genetic, although the swelling episodes are very much like those seen in HAE.

Hereditary angioedema type III is very similar to types I and II. However, HAE type III is caused by a change in the factor XII (FXII) gene, while HAE types I and II are caused by changes in the SERPING1 gene. HAE type III is also called hereditary angioedema with normal C1 inhibitor. C1 inhibitor is the protein that is deficient or does not function properly in HAE types I and II.

There are people with HAE that do not have changes in either the FXII or the SERPING1 genes, which means that at least one more genes can cause a form of HAE.

A characteristic and important feature of hereditary angioedema (HAE) is that when people have an episode of swelling, they usually do not have itching, a rash, or hives. This helps to distinguish HAE from an allergic reaction where swelling also occurs, but also is usually accompanied by itching and a rash or hives.