Alpha-mannosidosis

Teenagers with alpha-mannosidosis are not known to have any health problems that cause differences in stages of puberty.

Some people with alpha-mannosidosis have medical problems that can prevent them from living independently. However, alpha-mannosidosis is a variable disease and there may be some people who can live somewhat independently without help from others. Mental capacity based on the severity of disease is another factor that plays a big role in whether or not a person with alpha-mannosidosis may be able to live on their own.

Due to the buildup of complex sugars, or oligosaccharides, in the body of people with alpha-mannosidosis, thickening of the ligaments in the body puts pressure on various nerves. This pressure on the nerves in the hands can cause nerve damage and pain in the wrist called carpal tunnel syndrome.

Because of the skeletal problems that people with alpha-mannosidosis have, it is usually easy to tell if one of your family members could have this genetic condition; however, some people with alpha-mannosidosis may not have any signs or symptoms at birth. If anyone in your family has signs of alpha-mannosidosis or is a new full sibling to someone with alpha-mannosidosis, genetic testing may be helpful for them. Other people in the family could be carriers of alpha-mannosidosis, and a genetic counseling consultation might benefit them. Genetic counselors can be found on the National Society of Genetic Counselors website.

If you or a family member are diagnosed with alpha-mannosidosis, and genetic testing has confirmed your diagnosis, it is helpful to share your results with your family. A detailed family history can also provide information about which family members are at risk for developing alpha-mannosidosis.

You can find other people with alpha-mannosidosis online through different support groups like The National MPS Society, which provides support for people and families affected by mucopolysaccharidosis and other lysosomal storage disorders like alpha-mannosidosis. The MPS Society-UK also provides similar support. The International Society for Mannosidosis and Related Diseases is an international support resource for alpha-mannosidosis that can help connect patients together.

If you are interested in meeting other people with alpha-mannosidosis in person, this may be difficult since it is a rare genetic condition. However, if you see doctors that are familiar with mucopolysaccharidoses or other Lysosomal Storage Diseases, they may know other people with alpha-mannosidosis in your area that they can put you in contact with.

Pictures of people with alpha-mannosidosis can be often be found via support and information materials found on advocacy group websites. To see a few examples of these materials please visit ISMD, MPS Society, or MSP Society UK.

Caring for people with any long term condition can be tiring and challenging. This is no different for parents or other caregivers of people with alpha-mannosidosis. If you are a caregiver in need of support, try to take time for yourself, set aside time for personal counseling, or look for other resources at Caregiver Action.

Everyone with alpha-mannosidosis has some degree of intellectual disability, usually mild to moderate. There are some special services that can help these people with the learning problems associated with this condition. Many people with alpha-mannosidosis use sign language to help with educational and social learning for those with hearing loss, early educational intervention to help with social skills, speech therapy, and special education classes.

Because alpha-mannosidosis is a condition that affects various parts of the body, people with alpha-mannosidosis may need to see many specialists for their medical care. Some of these types of specialists can include orthopedists, medical geneticists, ophthalmologists, audiologists, otolaryngologists (or ENTs), neurologists, and surgeons. A center of excellence for lysosomal storage diseases may offer many specialists in one location. To find a doctor or center that specializes in metabolic genetic conditions or lysosomal storage disorders like alpha-mannosidosis in the United States, you can access the list of centers compiled by the National Mucopolysaccharidosis Society by visiting MPS Society resources and clicking the "MPS Genetic Centers." Even though this list is on a website focused on mucopolysaccharidoses, these doctors often specialize in many different types of lysosomal storage diseases, including alpha-mannosidosis.

Physical therapy including hydrotherapy can be used to decrease the strain on the joints of people with alpha-mannosidosis. Anti-inflammatory medications like ibuprofen can also be used to reduce some of the joint pain that people with alpha-mannosidosis may have. There are certain orthopedic surgeries that can be done to correct other skeletal problems, like knock knees, if necessary. Other interventions like special shoes for support or the use of a wheelchair can be considered. If a person with alpha-mannosidosis has osteopenia or osteoporosis found on imaging, the use of certain medications like palmidronate or zoledronic acid may be helpful. Talking with an orthopedic doctor or a physical therapist may be helpful in figuring out what management is best for you or your child with alpha-mannosidosis.

Hydrocephalus, or a blockage in fluid in the brain that causes pressure, can happen in people with alpha-mannosidosis at any age. If a person has symptoms of hydrocephalus like headaches or nausea and vomiting, an imaging scan called a CT scan can be done to look at the fluid in the brain. If this scan shows that someone with alpha-Mannosidosis has hydrocephalus, a thin tube called a shunt can be inserted so that it drains the blocked fluid from the brain. To learn more, you can talk to your doctor about the signs and symptoms of hydrocephalus and what to do should you see symptoms.

Some of the hearing problems associated with alpha-mannosidosis are made worse by frequent ear infections. There are medications people can take early to prevent and treat these types of infections. For people with alpha-mannosidosis that have conductive hearing loss, there are a few types of ear tubes that can be inserted surgically to remove fluid and improve hearing. For people with this condition that have sensorineural, or nerve, hearing loss, hearing aids can be used to improve hearing.

People with alpha-mannosidosis should have an eye doctor called an ophthalmologist who can check them regularly for vision and other eye problems. Corrective lenses can also help some of the vision problems associated with this condition. Medication or corneal transplants may help improve vision in people who have scarring of their corneas, or opacities, that can cause vision loss. If a person with alpha-mannosidosis has a cataract that is causing visual impairment, this may also be surgically removed. Most eye problems do not cause severe vision loss for people with alpha-mannosidosis but this can vary from person to person with this condition.

Historically, treatment for alpha-mannosidosis has mostly been based on treating and managing the different symptoms that people with the condition have.

A hematopoietic stem cell transplant (HSCT) can also be used to treat some of the symptoms of alpha-mannosidosis. These transplants can improve the levels of alpha-mannosidase in the body to treat some of the symptoms of the condition. A HSCT does not usually improve the problems with the bones, problems with the eyes, or the problems that people with alpha-mannosidosis can have with their mental development and the brain. HCST has significant risks to the person undergoing the procedure and is not done on a routine basis. The risks and benefits of HSCT should be discussed with your doctor.

Treatment options for alpha-mannosidosis using enzyme replacement therapy emerged in January 2018. The European Medicines Agency (EMA) granted a marketing authorization under exceptional circumstances in the European Union for Lamzede (velmanase alfa, Chiesi Farmaceutici S.p.A.) to treat alpha-mannosidosis. Lamzede is a long-term intravenous enzyme replacement therapy for adults, adolescents, and children with mild to moderate forms of alpha-mannosidosis. Details available from European Medicines Agency announcement.

In September 2022, Chiesi Global Rare Diseases announced that the U.S. Food and Drug Administration (FDA) accepted a Biologics License Application for velmanase alpha, Chiesi’s enzyme replacement therapy, for treating alpha-mannosidosis. Velmanase alpha was granted priority review, with the FDA setting an action date in the first half of 2023 under the Prescription Drug User Fee Act. The FDA gives priority review to therapies with the potential to provide important improvements in the diagnosis, prevention, or treatment of serious conditions. With this designation, the review period required by the FDA is shortened. To view more detailed information see the Chiesi Global Rare Diseases announcement.

People with alpha-mannosidosis can have ear problems including frequent ear infections and hearing loss. Medications can be given to treat ear infections and hearing aids or the insertion of ear tubes may help with some hearing loss depending on the cause. People with alpha-mannosidosis can also have frequent coughs, colds, and other throat infections. Vaccinations to prevent the flu and other respiratory infections can help avoid these problems. If breathing is made difficult by enlarged tonsils or adenoids, these can be surgically removed. As different people can have varying severity of disease, people with alpha-mannosidosis may have varying symptoms.

Alpha-mannosidosis is not usually abbreviated and is typically written as alpha-mannosidosis.

Gene therapy is a type of treatment for several genetic conditions where genetic instructions are used to treat or prevent disease. In the case of alpha-mannosidosis, gene therapy would potentially involve changing or blocking the incorrect genetic instructions of the MAN2B1 gene that are causing the disease of alpha-mannosidosis. Currently, gene therapy is not yet available as a treatment for people with alpha-mannosidosis. However, gene therapy for alpha-mannosidosis is something that is currently being researched.

Alpha-mannosidosis is a genetic condition that causes a progressive storage disorder in the body’s organs. Genetic changes or mutations in the MAN2B1 gene cause complex sugar molecules, called oligosaccharides, to build up in different parts of the body. This buildup of oligosaccharides causes health problems for people with alpha-mannosidosis, which is why it is called a storage disorder or, more specifically, a lysosomal storage disorder. The main health problems that result from the buildup of oligosaccharides in people with alpha-mannosidosis include intellectual disability, pronounced or "coarse" facial features, and skeletal issues like abnormally shaped back bones (vertebrae), thickened bones at the top of the skull, reduced bone density (osteopenia), bowed legs, and knock-knee abnormalities. People with alpha-mannosidosis can also have medical problems such as frequent infections, hearing loss, vision loss from cloudy corneas, enlargement of the liver and spleen, muscle weakness, and difficulties coordinating movement (ataxia).

The buildup of oligosaccharides in the body’s cells causes alpha-mannosidosis symptoms. The main symptoms of alpha-mannosidosis include intellectual disability, pronounced or "coarse" facial features, and skeletal problems like abnormally shaped back bones (vertebrae), thickened bones at the top of the skull, reduced bone density (osteopenia), bowed legs, and knock-knee abnormalities. People with alpha-mannosidosis can also have medical problems such as frequent infections, hearing loss, vision loss from cloudy corneas, enlargement of the liver and spleen, muscle weakness, and(issues coordinating movement (ataxia).

Genetic changes in the MAN2B1 gene prevent the normal production of the alpha-mannosidase enzyme. This lack of alpha-mannosidase causes the buildup of complex sugars, or oligosaccharides, in different parts of the body. The buildup of oligosaccharides can cause intellectual disability, pronounced or "coarse" facial features, and skeletal problems like abnormally shaped back bones (vertebrae), thickened bones at the top of the skull, reduced bone density (osteopenia), bowed legs, and knock-knee abnormalities. People with alpha-mannosidosis can also have medical problems such as frequent infections, hearing loss, vision loss from cloudy corneas, enlargement of the liver and spleen, muscle weakness, and difficulties coordinating movement (ataxia).

Alpha-mannosidosis is caused by a change (also called a mutation or a variant) in the MAN2B1 gene, which causes the gene not to work correctly. The MAN2B1 gene carries the instructions for making the alpha-mannosidase enzyme, which is essential for breaking down large sugar molecules in lysosomes within the body’s cells. We normally have two working copies of MAN2B1 in our cells, and we inherit one copy from our biological mother and the other from our biological father. To develop symptoms of alpha-mannosidosis, both copies of MAN2B1 are not working correctly. This is also called autosomal recessive inheritance, which means that both parents of someone with alpha-mannosidosis are carriers of one working and one non-working copy of the MAN2B1 gene. Since each parent has one working copy, they don’t have symptoms of alpha-mannosidosis themselves. However, when they have children, they each have a 1 in 2 or 50% chance of passing on the non-working copy to their child. When both parents are carriers, there is a 1 in 4 or 25% chance of both passing on the non-working copy and having a child with alpha-mannosidosis.

Alpha-mannosidosis is caused by a change (variant) in the MAN2B1 gene. Not all changes in a gene necessarily cause disease. If a change is known to cause a disorder, it is known as a pathogenic or disease-causing variant. However, sometimes gene changes are found, and scientists are unsure what it means, either because it has not been found before or has only been found in a few people. This is known as a variant of unknown significance. If you have a variant of unknown significance in the MAN2B1 gene, talk to your doctor about further testing that may help find out whether the gene change is pathogenic or not. A genetic counselor may also be able to help you review your test results. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website.

A "variant" is another word for a change in a gene. Sometimes these changes are not associated with causing a genetic disease or condition; other times, they are. Variants can be benign (not disease-causing), pathogenic (disease-causing), or of unknown significance (possibly disease-causing). Looking at a person’s genetic testing report can be helpful to know what type of variant or genetic change someone has inherited for alpha-mannosidosis. If a person has alpha-mannosidosis, they have two different disease-causing (pathogenic) variants in their MAN2B1 genes.

Alpha-mannosidosis is caused by a change (variant) in the MAN2B1 gene. Not all changes in a gene necessarily cause disease. If a change is known to cause a disorder, it is known as a pathogenic or disease-causing variant. However, sometimes gene changes are found, and scientists are unsure what it means, either because it has not been found before or it has only been found in a few people. This is known as a variant of unknown significance. If you have a variant of unknown significance in the MAN2B1 gene, talk to your doctor about further testing that may help find out whether the gene change is pathogenic or not. A genetic counselor may also be able to help you review your test results. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website.

If your child with alpha-mannosidosis is exhibiting behavioral problems, signs of depression, or other signs of a mental illness that could be related to having a long term illness, there are a few different resources that may be helpful for them. For behavioral problems, counseling or behavioral therapy may be useful. For depression or other mental illnesses, counseling by a psychologist or being treated by a psychiatrist may be helpful. If you are concerned about your child having behavioral problems, depression, or other signs of a mental illness, ask for a referral to a specialist who can help pinpoint the issue.

The buildup of oligosaccharides can cause individuals with alpha-mannosidosis to have many health problems, including intellectual disability, pronounced or "coarse" facial features, and skeletal issues like abnormally shaped back bones (vertebrae), thickened bones at the top of the skull, reduced bone density (osteopenia), bowed legs, and knock-knee abnormalities. People with alpha-mannosidosis can also have medical problems such as frequent infections, hearing loss, vision loss from cloudy corneas, enlargement of the liver and spleen, muscle weakness, and issues coordinating movement (ataxia).

People with alpha-mannosidosis can have abnormally shaped back bones, or vertebrae, that can cause a curve in the spine. They can also have thickened bones at the top of the skull. People with alpha-Mannosidosis can also have reduced bone density (osteopenia) or weakened bones (osteoporosis). Some people with alpha-mannosidosis have bowed legs and others have knock knee abnormalities, also called genu valgum.

People with alpha-mannosidosis can have ear problems, including frequent ear infections and hearing loss. People with this condition can also have frequent coughs, colds, and other throat infections. The tonsils, or the adenoids, can become enlarged in people with alpha-mannosidosis. Enlargement of the tonsils plus the buildup of storage material in the airway can cause problems with breathing.

If you and your partner are both carriers of alpha-mannosidosis, there is a 25% (1 in 4) chance for each of your children to be affected with alpha-mannosidosis. If you would like to have a more in depth discussion about inheritance, it may be helpful for you to speak with a genetic counselor. Genetic counselors can be found on the National Society of Genetic Counselors website.

Dysostosis multiplex is a medical term for a typical pattern of bone problems in people with mucopolysaccharidoses. These bone problems include abnormally shaped back bones (vertebrae) and ribs (spatulate), enlarged skull, too small and too thick leg bones (hypoplastic epiphyses and thickened diaphyses), and bullet-shaped finger and toe bones (metacarpals). Most people with alpha-mannosidosis have some mild to moderate dysostosis multiplex.

Not everyone with alpha-mannosidosis will have the same symptoms, the same age of onset, or the same severity of the disease. The symptoms of alpha-mannosidosis can be very different from one person to the next. This wide range of symptoms that can occur in other people with the same genetic condition is called variable expressivity. Even members of the same family with the same genetic change can have different features or disease severity.

Variable expressivity can be caused by differences in the genetic changes or mutations found in a gene. Depending on how the gene is changed, some mutations can be mild, and others can be very severe. A combination of other unknown factors, including other modifier genes, environmental influences, and lifestyle choices, also cause variable expressivity.

Newborn screening is a state-run program that screens babies for certain severe medical conditions at birth. Newborn screening is not currently being performed for alpha-mannosidosis. To learn about what conditions are being screened for in different states, visit: http://www.babysfirsttest.org/newborn-screening/states.

More information about newborn screening available in each state is available from the NewSTEPs Newborn Screening Status site, or the U.S. Centers for Disease Control and Prevention in Atlanta, Georgia.

There are different types of tests available to diagnose alpha-mannosidosis. One type of test looks at the levels of the alpha-mannosidase enzyme in the blood or skin cells and can determine if someone may have alpha-mannosidosis. Another way to test for alpha-mannosidosis is by doing a genetic test that looks for specific changes in the MAN2B1 gene in the blood.

Currently, enzyme replacement therapy (ERT) is clinically available for people with alpha-mannosidosis in Europe. Chiesi Global Rare Diseases is working with the FDA (Food and Drug Administration) for this therapy to become available in the United States.

In January 2018, the European Medicines Agency (EMA) granted a marketing authorization under exceptional circumstances in the European Union for Lamzede (velmanase alfa, Chiesi Farmaceutici S.p.A.) to treat alpha-mannosidosis. Lamzede is a long-term intravenous enzyme replacement therapy for adults, adolescents, and children with mild to moderate forms of alpha-mannosidosis. Details available from European Medicines Agency Announcement.

In September 2022, Chiesi Global Rare Diseases announced that the U.S. Food and Drug Administration (FDA) accepted a Biologics License Application for velmanase alpha, Chiesi’s enzyme replacement therapy, for treating alpha-mannosidosis. Velmanase alpha was granted priority review, with the FDA setting an action date in the first half of 2023 under the Prescription Drug User Fee Act. The FDA gives priority review to therapies with the potential to provide important improvements in the diagnosis, prevention, or treatment of serious conditions. With this designation, the review period required by the FDA is shortened. To view more detailed information see the Chiesi Global Rare Diseases announcement.

Currently, there is clinical research studying the usefulness of certain drugs in people with alpha-mannosidosis, as well as long-term information about the natural history of the disease in people with alpha-mannosidosis. For up-to-date information on clinical trials, visit clinicalgrials.gov and search for alpha-mannosidosis.

Treatment for alpha-mannosidosis is mainly based on treating the different symptoms that people with the condition have. A hematopoietic stem cell transplant (HSCT) can also treat some of the symptoms of alpha-mannosidosis. These transplants can improve alpha-mannosidase levels in the body to treat some of the symptoms of the condition. A HSCT does not usually improve the problems with the bones, problems with the eyes, or the problems that people with alpha-mannosidosis can have with their mental development and the brain. HCST has significant risks to the person undergoing the procedure and is not done on a routine basis. The risks and benefits of HSCT should be discussed with your doctor.

Treatment options for alpha-mannosidosis using enzyme replacement therapy emerged in January 2018.The European Medicines Agency (EMA) granted marketing authorization under exceptional circumstances in the European Union for Lamzede (velmanase alfa, Chiesi Farmaceutici S.p.A.) to treat alpha-mannosidosis. Lamzede is a long-term intravenous enzyme replacement therapy for adults, adolescents, and children with mild to moderate forms of alpha-mannosidosis. Details available from European Medicines Agency announcement.

In September 2022, Chiesi Global Rare Diseases announced that the U.S. Food and Drug Administration (FDA) accepted a Biologics License Application for velmanase alpha, Chiesi’s enzyme replacement therapy, for treating alpha-mannosidosis. Velmanase alpha was granted priority review, with the FDA setting an action date in the first half of 2023 under the Prescription Drug User Fee Act. The FDA gives priority review to therapies with the potential to provide important improvements in the diagnosis, prevention, or treatment of serious conditions. With this designation, the review period required by the FDA is shortened. To view more detailed information see the Chiesi Global Rare Diseases announcement.

Currently, there are no specific diets recommended for people with alpha-mannosidosis. Dieticians, nutritionists, and other doctors can help determine if specific diet changes may be helpful for people with alpha-mannosidosis depending on their individual symptoms.

Genetic changes in the MAN2B1 gene are the cause of alpha-mannosidosis.

Currently, there is no gene therapy available to treat people with alpha-mannosidosis. However, gene therapy done in humans with alpha-mannosidosis may be a possibility for treatment in the near future. Some research studies show that gene therapy helped treat alpha-mannosidosis in cats with this condition.

Some animals, such as cats and guinea pigs, can also have a condition like alpha-mannosidosis caused by low levels of the alpha-mannosidase enzyme.

Currently, there are no case reports in the literature of a woman with alpha-mannosidosis reproducing. In theory, however, if two people with alpha-mannosidosis have a child, all of their children will also have alpha-mannosidosis. This is because the parents do not have genetic instructions for the working alpha-mannosidase enzyme for their children to inherit.

Genetic changes in the MAN2B1 gene associated with alpha-mannosidosis cause alpha-mannosidosis. MAN2B1 is not a predisposition gene for alpha-mannosidosis.

Alpha-mannosidosis affects different people differently and not all children with alpha-mannosidosis will show signs of the condition before birth. There are 3 different types of alpha-mannosidosis. Alpha-mannosidosis types 1 and 2 do not usually cause medical problems for the affected person before birth. In the case of people who have alpha-mannosidosis type 3, the most severe type of the condition, skeletal abnormalities, muscle weakness, and problems with the brain and nervous system can be present before or shortly after birth. This is the main reason why people with alpha-mannosidosis Type 3 can pass away before birth or shortly after birth.

If more than one person in the same family has alpha-mannosidosis and the same genetic changes that cause the condition, that does not necessarily mean that they will all have the same symptoms or severity of the condition. This is because alpha-mannosidosis is a variable condition that affects different people differently.

If you have alpha-mannosidosis, your doctor should know that this is a progressive condition affecting multiple body organ systems. Your doctor should also know that alpha-mannosidosis is a genetic condition that is inherited in an autosomal recessive pattern. This information can help your doctor learn how to best care for you and who else in your family may need to be tested for alpha-mannosidosis.

If you are concerned about having a baby with alpha-mannosidosis, there are certain procedures a person can have during or before their pregnancy to find out if their baby is at risk for alpha-mannosidosis. In general, genetic testing is only available during a pregnancy when the genetic changes have already been found in the family. Some of these include vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD), chorionic villus sampling (CVS), or an amniocentesis. A medical geneticist or a genetic counselor can help talk to you about these options and what information may be needed before you can have a procedure like one of these. Genetic counselors can be found on the National Society of Genetic Counselors website.

If you are a carrier of alpha-mannosidosis, your future children will each have a 25% (1 in 4) chance to have alpha-mannosidosis only if your partner is also a carrier of the condition. Your partner can have testing to determine if they are a carrier of alpha-mannosidosis and, therefore, if any children you have together could have this condition.

If you are a carrier of alpha-mannosidosis and your partner is not, your children would each have a 50% (1 in 2) chance to be a carrier of this condition just like you. If one of your children is a carrier and their partner is also a carrier, each of their children will have a 25% (1 in 4) chance to have alpha-mannosidosis.

There are three different forms of alpha-mannosidosis. Alpha-mannosidosis type 1 is a mild form of the condition where people usually show signs after 10 years of age. Alpha-mannosidosis type 2 is a moderate form of the condition where people usually show signs before age 10. Alpha-mannosidosis type 3 is the most severe form of the condition where people usually die before birth or at a very young age. Because different people with alpha-mannosidosis have differences in the severity of their disease, it is difficult to know exactly at which point of early childhood a person may start showing signs of this condition if they have alpha-mannosidosis type 1 or type 2.

The average cost of a hematopoietic stem cell transplant (HSCT) is between $350,000- 800,000 in the United States. This is the estimated cost if a person did not have insurance, but depending on the health insurance plan that a person with alpha-mannosidosis has, the cost may be much less. To learn more about the cost of this procedure, call your insurance company to discuss coverage and cost.

Normal levels of alpha-mannosidase in the body is determined by an accepted range at certain laboratories that perform this testing. The number for the normal "cutoff" may be different at different labs because of this and can also be different depending on what type of tissue is used for the testing (white blood cells, cultured skin cells, etc.). The "cutoff" should be listed on the testing result no matter what type of sample was used. For instance, the Mayo Clinic Mayo Medical Laboratories quotes the normal range to be anything more than 0.54 nanomoles per milligram of protein in cultured skin cells. Regardless of the "cutoff" number, alpha-mannosidase testing would tell if a person’s enzyme levels are below the normal range enough to be concerning for alpha-mannosidosis.

It is estimated that about 1 in every 500,000 people have alpha-mannosidosis.

There are three different forms of alpha-mannosidosis. Alpha-mannosidosis type 1 is a mild form of the condition where people usually show signs after 10 years of age with a slow progression of the disease. alpha-mannosidosis type 2 is a moderate form of the condition where people usually show signs before age 10 with a slow progression of disease. Alpha-mannosidosis type 3 is the most severe form of the condition. People with alpha-mannosidosis type 3 usually die before birth or at a young age because of significant and progressive problems with the brain and other parts of the nervous system. People with type 1 or 2 alpha-mannosidosis can have a reasonably normal lifespan with good medical care depending on the severity of their medical problems from the condition. Many adults with alpha-mannosidosis type 1 or type 2 are over 50 years of age. As lifespan and the severity of disease can vary from person to person, people can ask their physician for more personalized information.

Alpha-mannosidosis is inherited in an autosomal recessive inheritance pattern. We have two copies of the MAN2B1 gene, one from each parent. Both parents of a child with alpha-mannosidosis must pass a nonworking copy of the MAN2B1 to that child. People with one working copy and one nonworking copy of the MAN2B1 gene are carriers of alpha-mannosidosis and do not have the condition. If two carriers have a child, there is a 1 in 4 chance that the child will have alpha-mannosidosis. If you have questions about the family members in your family who might be at risk of having alpha-mannosidosis or be a carrier for alpha-mannosidosis, you may contact a genetic counselor near you by looking at the National Society of Genetic Counselors home page. You may contact a genetic counselor by using the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

If you are unable to find a support group in your area or online that is helpful to you, you can start your own support group. First, talk to other support group leaders and see if they have helpful information. You also may want to look for resources that your group may need before you start your support group. If you want to start a support group online, you may be interested in using social media platforms such as Yahoo!, Groups, or Facebook to connect with others. If you want to start a support group in person for alpha-mannosidosis, this may be challenging since this is a rare genetic condition.

People with alpha-mannosidosis usually get their two genetic changes in the MAN2B1 gene that causes this condition from their parents. One of these genetic changes comes from each of their parents and this makes their parents "carriers" of alpha-mannosidosis. Carriers of a condition usually don’t have medical problems, but can have a child with the condition if both parents are carriers. To find out if you are a carrier, you can talk to a doctor or a genetic counselor about carrier testing for alpha-mannosidosis and other genetic conditions. If you are found to be a carrier of alpha-mannosidosis, you have a 25% chance (1 in 4) to have a child with alpha-mannosidosis if your partner is also a carrier of alpha-mannosidosis. Genetic counselors can be found on the National Society of Genetic Counselors website.

Donations that go towards research for cures for mucopolysaccharidoses and other lysosomal storage diseases, including alpha-mannosidosis, can be submitted online or by mail to the Mucopolysaccharidosis (MPS) Society. You can also donate to the MPS Society-UK. The International Society for Mannosidosis and Related Diseases also accepts donations. Money for research in a particular group of conditions that includes mucopolysaccharidosis through. You can also donate money for research in a specific group of diseases that includes mucopolysaccharidosis through the National Organization for Rare Disorders.

To get tested for alpha-mannosidosis, visit a doctor or a genetic counselor near you. Let your doctor or genetic counselor know you are concerned about a genetic condition like alpha-mannosidosis. A physician or genetic counselor can help decide if testing for alpha-mannosidosis is right for you. To find a medical genetics professional near you to discuss genetic testing visit the Find a Medical Geneticist/Clinic Tool. on the American College of Medical Genetics and Genomics website. To find a genetic counselor near you, visit the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website.

You can find clinical research opportunities in alpha-mannosidosis online by going to www.clinicaltrials.gov and searching for "alpha-mannosidosis" in the search box on the home page. This will show you ongoing clinical trials and those currently recruiting people to participate, in addition to recently completed trials.

There are not centers of excellence specifically for alpha-mannosidosis, but there are several centers of excellence in the United States and other countries for lysosomal storage disorders, including alpha-mannosidosis. To find a doctor or center that specializes in metabolic genetic conditions, or lysosomal storage disorders like alpha-mannosidosis in the United States, you can access the list of centers compiled by the National Mucopolysaccharidosis Society by visiting MPS Society resources and clicking the "MPS Genetic Centers." Even though this list is on a website focused on mucopolysaccharidoses, these doctors often specialize in many different types of lysosomal storage diseases, including alpha-mannosidosis.

To find a doctor or center that specializes in metabolic genetic conditions or lysosomal storage disorders like alpha-mannosidosis in the United States, you can access the list of centers compiled by the National Mucopolysaccharidosis Society by visiting MPS Society-Resources and clicking the "MPS Genetic Centers." Even though this list is on a website focused on mucopolysaccharidoses, these doctors often specialize in many different types of lysosomal storage diseases, including alpha-mannosidosis.

You can provide your doctor with education materials such as the information booklets on alpha-mannosidosis found at Orphanet Journal of Rare Diseases, NORD-Alpha mannosidosis, or National Library of Medicine. If you would like to see or speak to a professional who has experience with alpha-mannosidosis, ask your doctor to help you locate an expert. To find a medical genetics professional near you visit the Find a Medical Geneticist/Clinic Tool on the American College of Medical Genetics and Genomics website. To find a genetic counselor near you visit the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website.

Hydrotherapy is the use of water to treat or prevent a disease. Performing physical exercises in water may reduce some of the strain on the joints that people with alpha-mannosidosis can have. The use of steam to reduce mucus in the chest is another form of hydrotherapy that can be helpful for people with alpha-mannosidosis.

An amniocentesis is a procedure during pregnancy where some of the amniotic fluid is removed from around the baby and is tested. This fluid can be tested for alpha-mannosidase enzyme levels to see if the baby has a problem with their enzyme levels and, therefore, could have alpha-mannosidosis. If there are known genetic changes for alpha-mannosidosis in the family, genetic testing could also be done on the amniotic fluid to see if the baby has two changes for alpha-mannosidosis, meaning that they have this condition. Talk to a doctor or a genetic counselor about the possibility of this testing if it is something you are interested in learning more about. Genetic counselors can be found on the National Society of Genetic Counselors website.

A hematopoietic stem cell transplant, or HSCT, replaces the missing alpha-mannosidase enzyme in people with alpha-mannosidosis. This can improve some of the symptoms of alpha-mannosidosis like a large liver and spleen, frequency of infections, and hearing loss. A HSCT does not usually improve the problems with the bones, problems with the eyes, or the problems with mental development and the brain. Since alpha-mannosidosis is a progressive condition, having a HSCT is considered to be most beneficial early on in life. HSCT is not done routinely and is a risky procedure. There are some reports of people with alpha-mannosidosis having successful HCST and other reports of people with this condition not having a successful HCST. HCST has significant risks to the person undergoing the procedure. The risks and benefits of HSCT should be discussed with your doctor.

A chorionic villus sampling, or CVS, is a procedure during pregnancy where some of the finger-like pieces, or villi, of the placenta are removed and tested. If there are known genetic changes for alpha-mannosidosis in the family, genetic testing could be done on these villi to see if the baby has two changes for alpha-mannosidosis, meaning that they have this condition. Talk to a doctor or a genetic counselor about the possibility of this testing if it is something you are interested in learning more about.

There are some specific genetic changes that are associated with the more severe form of alpha-mannosidosis, but other genetic changes have been found in both people with the severe form of alpha-mannosidosis and people with the mild form of alpha-mannosidosis. Because of this, it is hard to know what form of the condition or what symptoms of alpha-mannosidosis a person might have by just looking at their genetic changes. If you have a genetic testing result for the MAN2B1 gene and want to know more information about what those changes mean, talk to a genetic counselor. Genetic counselors can be found on the National Society of Genetic Counselors website.

Because most people with alpha-mannosidosis have two genetic changes in their MAN2B1 genes in all of the cells of their body, they would have the same genetic testing results on blood, saliva, or other body tissue from a biopsy. However, most genetic tests for alpha-mannosidosis are done on the blood.

Many people with alpha-mannosidosis have an enlarged liver or spleen because of the build up of complex sugars, called oligosaccharides. Having an enlarged liver or spleen usually does not cause medical problems, but can sometimes cause issues with eating or breathing. People with an enlarged spleen may be encouraged to avoid contact sports or other activities where their spleen could be injured.

Alpha-mannosidosis is a condition that affects different people differently. However, almost everyone with alpha-mannosidosis has some skeletal problems that affects the way that their bones form. The most common skeletal problems that people with alpha-mannosidosis have are abnormally shaped back bones (vertebrae), thickened bones at the top of the skull, reduced bone density (osteopenia), bowed legs, and knock-knee abnormalities.

Different people with alpha-mannosidosis will have different symptoms of this condition. One research study in 2007 found that about 25% (1 in 4) of people with alpha-mannosidosis had some type of psychiatric medical concern. The most common psychiatric problems that people with alpha-mannosidosis have are confusion, delusions, hallucinations, anxiety, and depression. For those people with psychiatric concerns, the usual age of onset was late puberty to early adolescence.

Hydrocephalus is something that can happen when the fluid in the brain and the spinal cord becomes blocked and causes increased pressure on the head. Hydrocephalus can occur in some people with alpha-mannosidosis at any age, but this is not something that all people with alpha-mannosidosis will have. There are scans, called CT scans, that can look at the fluid in the brain to see if a person with alpha-mannosidosis has hydrocephalus.

Moderate to severe hearing loss is common in people with alpha-mannosidosis, but there may be people with this condition who do not have hearing loss. This is because different people with alpha-mannosidosis may have different symptoms of this condition. In order to learn more about hearing loss and evaluations for hearing loss, contact an audiologist or request a referral to a hearing specialist from your physician.

When people with alpha-mannosidosis are born, they may be larger than other children their age or growth faster than other children in the first few years of life. However, as people with alpha-mannosidosis get older, they may have growth restriction, or not grow as much as others. A person with alpha-mannosidosis will have their growth checked at every visit with their physician. The physician will monitor for delayed or abnormal growth. If you have a concern about abnormal growth, ask you or your child’s physician to discuss growth progress .

Eye problems that cause vision loss are common for people with alpha-mannosidosis, but there are some people with this condition who will not have vision loss. The most common eye problems in alpha-mannosidosis are scarring of the corneas, called opacities and cataracts. These eye problems can cause problems with vision. Vision loss is usually not severe in people with alpha-mannosidosis, but vision can be somewhat impaired from these eye problems. Many vision problems in people with alpha-mannosidosis can be treated or managed. To learn more about these vision concerns and treatments, it may be useful to speak with a vision specialist, or ophthalmologist.

Alpha-mannosidosis is caused by changes in the MAN2B1 gene which results in a buildup of complex sugars, called oligosaccharides. Most people with alpha-mannosidosis have an enlarged liver and spleen because of the buildup of oligosaccharides. Having an enlarged liver and spleen is called hepatosplenomegaly. Even though most people with alpha-mannosidosis will have an enlarged liver and spleen, there may be some affected individuals with this condition who do not have this medical issue.

Currently, there are no known environmental, pharmaceutical, or other factors that may make this condition more severe.

A hematopoietic stem cell transplant (HSCT) can improve the levels of alpha-mannosidase in the body to treat some of the symptoms of alpha-mannosidosis. A HSCT does not usually improve the problems with the bones, problems with the eyes, or the problems with mental development and the brain. While a HCST can improve some of the medical problems and quality of life issues for people with alpha-mannosidosis, a HCST has significant risks to the person undergoing the procedure, including the possibility of death. For this reason, it is difficult to say whether or not having an HSCT would extend the lifespan of a person with alpha-mannosidosis. This is complicated more by the fact that different people with alpha-mannosidosis have different severities of symptoms. Currently, there is no research about the effect of HSCT on lifespan in people with this condition. The risks and benefits of HSCT should be discussed with your doctor.

People with alpha-mannosidosis can have a buildup of complex sugars, called oligosaccharides, in different parts of the body, including the brain. As a result of this buildup, everyone with alpha-mannosidosis will have some degree of intellectual disability. There is a range, or spectrum, of intellectual disability in people with this condition depending on how severely they are affected. People with alpha-mannosidosis type 1 and type 2 usually have mild to moderate intellectual disability. The first signs of delays in people with alpha-mannosidosis are usually speech and motor delays, but development may vary in different people with this condition. In order to learn more about alpha-mannosidosis and intellectual disability, it may be helpful for people to speak with a developmental specialist or ask their physician for a referral to a specialist.

Many children with alpha-mannosidosis have problems with speech or do not speak at the same time that other children usually start speaking. For this reason, speech therapy may be helpful for some of people with this condition early on in their development. Talking with a doctor or speech therapist can give you more information about whether speech therapy may be helpful for your family member with alpha-mannosidosis.

Physical therapy can help with some of the joint pain and stiffness that people with alpha-mannosidosis can experience. A physical therapist can also help a person with alpha-mannosidosis be as active as possible without causing joint pain so they can improve their joint function and overall health.

There are currently no clinical trials or published research articles describing the use of growth hormone for people with alpha-mannosidosis. Growth hormone is usually not part of the standard management for people with alpha-mannosidosis, but talk with your doctor if this is something you would like more information about.

Alpha-mannosidosis does not affect a person’s ability to get pregnant or have a child. However, since people with alpha-mannosidosis may have severe medical problems, and all have some degree of intellectual disability, it is not very common for people with alpha-mannosidosis to have children of their own.

Occupational therapy may not directly improve the symptoms of alpha-mannosidosis; however, it can help some people with this condition learn developmental skills or other adaptive techniques. Talk with a doctor or occupational therapist to see if occupational therapy could be helpful to improve the day-to-day life of your family members with alpha-mannosidosis.

Determining if someone is a carrier of alpha-mannosidosis by looking at their alpha-mannosidase enzyme levels in the blood or in skin cells is possible, but can be unreliable. However, another form of carrier testing for alpha-mannosidosis is done by genetic testing that looks for changes in a person’s MAN2B1 genes. This is a more reliable and conclusive test to determine if someone is a carrier for alpha-mannosidosis.

A bone marrow transplant is a type of hematopoietic stem cell transplant or HSCT. A HSCT replaces the missing alpha-mannosidase enzyme in people with alpha-mannosidosis. This can improve some of the symptoms of alpha-mannosidosis, like a large liver and spleen, frequency of infections, and hearing loss. A HSCT does not usually improve the problems with the bones, problems with the eyes, or the problems that people with alpha-mannosidosis can have with their mental development and the brain. Since alpha-mannosidosis is a progressive condition, having a HSCT is considered the most beneficial early in life. There are some reports of people with alpha-mannosidosis having successful HCST and other reports of people with this condition not having a successful HCST. HCST also has significant risks to the person undergoing the procedure. The risks and benefits of HSCT should be discussed with your doctor.

The need to make modifications to the home of a person with alpha-mannosidosis is different from person to person with this condition. Some people with alpha-mannosidosis may be in wheelchairs and need specific home modifications related to this mobility restriction. People may wish to discuss special needs or home modifications with their child’s physician or request that they be referred to a specialist.

Children with alpha-mannosidosis may need specific and individualized resources in school, particularly related to their learning difficulties and intellectual disabilities. These may include special education, physically accessible modifications (depending on the person’s mobility), the use of sign language for hearing impaired students, or individual assistance for their school needs. It is important that your school and their staff know about your child’s needs so that they can make sure resources are made available.

Some children will need special accommodations in school. They are eligible for an individual education plan (IEP) or a 504 plan. An IEP is a document that helps to guide the education of a child with a disability or special needs. The plan is individualized for each student. A 504 plan ensures that students with disabilities can fully participate in school and access the same educational opportunities as all children. Parents are encouraged to provide a school with a packet of information on MPS IV and to work with school officials, including teachers, nurses, psychologists, the principal, and other professionals.

The U.S. Department of Education has information on individual education plans and on 504 plans. The National MPS Society also provides Education Strategies and Resources: A Guide for Parents to help children succeed at school.

Treatment for alpha-mannosidosis is mostly based on treating and managing the different symptoms that people with the condition have. However, in recent years, newer treatment options have arisen.

A hematopoietic stem cell transplant (HSCT) can also be used to treat some of the symptoms of alpha-mannosidosis. These transplants can improve the levels of alpha-mannosidase in the body to treat some of the symptoms of the condition. A HSCT does not usually improve the problems with the bones, problems with the eyes, or the problems that people with alpha-mannosidosis can have with their mental development and the brain. HCST has significant risks to the person undergoing the procedure and is not done on a routine basis. The risks and benefits of HSCT should be discussed with your doctor.

There are orthopedic surgeries that individuals with alpha-mannosidosis can have to relieve some of the pain and other complications from their bone problems. There are antibiotics and vaccinations available for people with alpha-mannosidosis that can prevent some of the infections that may be common for people with this condition. Hearing aids can be used to improve nerve related hearing loss, and glasses can be used to help with vision problems.

Depending on a person’s specific symptoms of Alpha-mannosidosis, there may be other treatment methods that they might find helpful.

Treatment options for alpha-mannosidosis using enzyme replacement therapy emerged in January 2018. The European Medicines Agency (EMA) granted a marketing authorization under exceptional circumstances in the European Union for Lamzede (velmanase alfa, Chiesi Farmaceutici S.p.A.) to treat alpha-mannosidosis. Lamzede is a long-term intravenous enzyme replacement therapy for adults, adolescents, and children with mild to moderate forms of alpha-mannosidosis. Details available from European Medicines Agency announcement.

In September 2022, Chiesi Global Rare Diseases announced that the U.S. Food and Drug Administration (FDA) accepted a Biologics License Application for velmanase alpha, Chiesi’s enzyme replacement therapy, for treating alpha-mannosidosis. Velmanase alpha was granted priority review, with the FDA setting an action date in the first half of 2023 under the Prescription Drug User Fee Act. The FDA gives priority review to therapies with the potential to provide important improvements in the diagnosis, prevention, or treatment of serious conditions. With this designation, the review period required by the FDA is shortened. To view more detailed information see the Chiesi Global Rare Diseases announcement.

Some of the other names for alpha-mannosidosis include alpha-mannosidase B Deficiency, and Lysosomal alpha-D-Mannosidase Deficiency.

In addition to corneal opacities, some people with alpha-mannosidosis can have cataracts. People with this condition that have had a corneal transplant can also have an astigmatism after the surgery. These eye problems are not usually associated with severe vision loss, but this can vary between different people with alpha-mannosidosis. Vision management and care is usually tailored to each person depending on their symptoms. If you have additional questions about vision treatments and management for alpha-mannosidosis, consider speaking to an ophthalmologist about how to best manage your or your child’s care.

Currently, there are no other genetic conditions known where a person has low levels of alpha-mannosidase besides alpha-mannosidosis. Because of this, a low level of alpha-mannosidase on a blood test is diagnostic for alpha-mannosidosis.

A few key features of people with alpha-mannosidosis distinguish them from those with other genetic conditions. People with alpha-mannosidosis have unique "coarse" facial features from the buildup of oligosaccharides caused by genetic changes in the MAN2B1 gene, which causes the face to look more pronounced and full than usual. The buildup of oligosaccharides can also cause corneal scarring, or opacities, in the eye and problems in the brain with learning and development. However, many of these symptoms of alpha-mannosidosis can be found in many lysosomal storage conditions.

There are several support groups available for people with alpha-mannosidosis online. The National MPS Society provides support for people and families affected by mucopolysaccharidosis and other lysosomal storage disorders like alpha-mannosidosis. The MPS Society-UK also provides similar support. The International Society for Mannosidosis and Related Diseases is an international support resource for alpha-mannosidosis. In addition, visit Discover Alpha-Mannosidosis for patient and caregiver resources.

There are three different forms of alpha-mannosidosis. Alpha mannosidosis type 1 is the mildest form of the condition and is characterized by onset after age ten, absence of skeletal abnormalities, and slow disease progression. Alpha-mannosidosis type 2 is a moderate form of the condition where people usually show signs of the condition before age ten, and symptoms include skeletal problems and muscle weakness, as well as a slowly progressing disease. Alpha-mannosidosis type 3 is the most severe form of the condition. Individuals affected with alpha-mannosidosis type 3 usually die before birth or at a young age because of progressive problems with the brain and other parts of the nervous system

The physical restrictions of people with alpha-mannosidosis are unique to each person’s symptoms and severity of disease. People with alpha-mannosidosis should avoid physical activities that cause them pain. Some people with an enlarged spleen or other medical complications may be encouraged to avoid contact sports.

Some people with alpha-mannosidosis have medical problems that may prevent them from being able to work. However, alpha-mannosidosis is a variable disease and there are some people with this condition that can work depending on their physical and mental capabilities. The Americans with Disabilities Act gives assistance to employers and employees so that people with alpha-mannosidosis can be successful in their work despite physical or intellectual disabilities. If you are interested in learning about work opportunities for yourself or your child with alpha-mannosidosis, it may be helpful to discuss options with a social worker.

Depending on the severity of symptoms of their condition, a doctor may recommend certain surgeries to a person with alpha-mannosidosis. Some people with alpha-mannosidosis have surgeries to treat some of their skeletal problems, to remove the tonsils or adenoids in the throat, to insert a tube (shunt) to remove the blockage of fluid around the brain and spinal cord, and for other reasons. Each surgery a person with alpha-mannosidosis has should be discussed with a doctor who is knowledgeable about their condition before they have the procedure.

Some of the features found in people with alpha-mannosidosis, such as skeletal changes, intellectual disability, pronounced or "coarse" facial features, and loss of control of body movements (ataxia), can also be found in some other genetic conditions. In particular, the symptoms of alpha-mannosidosis may be confused with mucopolysaccharidosis type I and other lysosomal storage diseases. However, alpha-mannosidosis can be distinguished from other storage disorders by enzyme or genetic testing done on the blood or other cells.

Fertility, or the ability to become pregnant, is not known to be affected in people with alpha-mannosidosis. However, most people with alpha-mannosidosis do not have children because of their medical problems or intellectual disability. Currently, there are no case reports in the literature of a woman with alpha-mannosidosis reproducing.

Recurring ear and sinus infections are common in people with alpha-mannosidosis. Because of the airway problems that some people with this condition can have, respiratory infections can also be common. For this reason, flu and other vaccines that protect against these types of infections should be considered for people with alpha-mannosidosis.