Homocystinuria

Some people with homocystinuria have intellectual problems and some of them do not. There is no way to know if someone will have an intellectual disability. There is no way to prevent it. Early treatment can reduce the risk. It is important for the individual with homocystinuria to be started on treatment as soon as possible. Talk to a doctor about treatment options available for homocystinuria. A medical geneticist is the type of doctor who treats homocystinuria. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website.

Homocystinuria occurs when an enzyme called cystathionine beta-synthase (CBS) does not work correctly. This enzyme is responsible for breaking down certain building blocks in the body. People who are B6-responsive have enzymes that still work a little bit. The enzymes do not work as well as they should, but still do some work. This can prevent some of the symptoms of the disorder. People who are B6-non-responsive have enzymes that do not work at all. Contact a genetic counselor to learn more about homocystinuria. To find a genetic counselor near you, use the Find a Genetic Counselor tool on the National Society of Genetic Counselors’ website.

The formula that your doctor prescribes is an amino acid mixture. Amino acids are building blocks for the body. People with homocystinuria need a special diet. This diet is low in amino acids that their bodies can’t process. Unfortunately, these diets are also low in amino acids that their bodies need. The medical formula has the missing amino acids that they need. Other medicines are also used to help process the amino acids that are harmful in this disorder. These medicines include Betaine, vitamin B12, folic acid, and vitamin B6. Talk to your doctor about which medicines you need. A medical geneticist is a doctor who treats homocystinuria. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website.

To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

Siblings of people with homocystinuria have a 25% chance to have homocystinuria. Siblings should be tested to see if they are affected. The parents of affected people are carriers (have one gene change). Carriers will not have symptoms. It is possible that one parent is affected with homocystinuria, but has only mild symptoms. The parents of an affected person should have a physical exam and blood work. If a person with homocystinuria has children with a carrier, they have a 50% chance to have an affected child. Partners of affected people should have carrier testing. If the partner of an affected person is not a carrier, then their children will be carriers. If two people with homocystinuria have children, then all of their children will also be affected. Their children should see a doctor for diagnosis and treatment. Talk with a genetic counselor to find out the risk to your family members. To find a genetic counselor near you, use the Find a Genetic Counselor tool on the National Society of Genetic Counselors’ website.

Below is a list of websites where you can find other people with homocystinuria:

Baby’s First Test
The Genetic and Rare Diseases Information Center

A medical geneticist, genetic counselor, dietician, and ophthalmologist (eye doctor) should be part of your medical team. Medical geneticists are doctors with special training in genetics. They can diagnose and treat homocystinuria. They will work with a dietician to help affected people plan the best diet. Other medical specialists may be needed to treat certain symptoms. An ophthalmologist treats eye problems that are sometimes seen in homocystinuria. A genetic counselor is trained in genetics and can assist in genetic testing and counseling. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website. To find a genetic counselor near you, use the Find a Genetic Counselor tool on the National Society of Genetic Counselors’ website.

A genetic counselor can discuss homocystinuria with you and provide the information you need. To find a genetic counselor near you, use the Find a Genetic Counselor tool on the National Society of Genetic Counselors’ website. If there are no genetic counselors in your area, you may be able to talk with one over the phone. Some genetic counselors are available for phone consults. Medical geneticists are doctors who specialize in genetic disorders. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website. If your doctor is not familiar with homocystinuria, provide them with contact information to these specialists.

Homocystinuria is sometimes shortened to HCY or HCU. HCY can also be used for the amino acid homocysteine. Be sure to check for a sentence that says they are shortening homocystinuria to HCY in any document you are reading.

People with homocystinuria can live a normal life span if they are treated. However, blood clots (thromboembolism) are the major cause of early death. Blood clots can block blood flow to the body’s organs leading to a risk of death. To learn more about the risks of homocystinuria, talk to your doctor or find a genetic counselor near you using the Find a Genetic Counselor Tool on the National Society of Genetic Counselors website.

Some people with homocystinuria show improvement when taking Vitamin B6 (pyridoxine). If testing shows that someone has homocystinuria, a pyridoxine test can be done. This is called a pyridoxine challenge. This test is done by measuring the levels of certain building blocks (amino acids) in the blood. The patient is then given a dose of pyridoxine. Amino acid levels are then measured again to see if they have gotten lower. If they have, then the patient is a responder. Responders are given pyridoxine as a treatment to reduce their symptoms. Some non-responders are also given pyridoxine. It is unclear if this treatment helps non-responders. Since the treatment is not harmful, it may be given anyway in case it is useful. Talk to your doctor to see if pyridoxine treatment is appropriate. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website.

Homocystinuria is an inherited disorder. In this disorder, the body is unable to process some of the building blocks of the body. These building blocks, called amino acids, make up proteins. Proteins perform many of the body’s functions and make up its structure. In homocystinuria, an enzyme called cystathionine beta-synthase (CBS) is needed to break down amino acids called methionine and homocysteine. When CBS is missing, these amino acids are not broken down correctly and build up in the body. High homocysteine levels can lead to health problems. Multiple forms of homocystinuria exist. They have different signs, symptoms and genetic causes. Symptoms include problems with the eyes, skeletal system, blood, and brain. Symptoms can vary and not all affected people have all of the findings. The severity of the symptoms can also vary. Some people with a mild form may not show symptoms until childhood or adulthood. People with severe forms can show symptoms as babies.

Symptoms of Homocystinuria can include:

Betaine is a medicine that helps change the amino acid homocysteine back to methionine. High levels of these amino acids cause the symptoms of homocystinuria. Betaine will lower homocysteine levels, but raise methionine levels. It is often given to people who do not follow their diet. It is also given to B6-non-responders who do not improve on the diet alone. Talk to your doctor to see if Betaine is needed. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website.

When there is a change (mutation) in the CBS gene, the enzyme cystathionine beta-synthase (CBS) is not produced correctly by the body. Enzymes are needed to process the building blocks of the body. The CBS enzyme is responsible for the breakdown of certain amino acids. These amino acids are called methionine and homocysteine. When CBS enzyme is absent, these amino acids build up in the body. High levels of these amino acids causes damage to the body. You can ask your doctor or genetic counselor about testing for high levels of these amino acids. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

There are different forms of homocystinuria. Different types have different causes. Homocystinuria can be caused by mutations in the CBS, MTHFR, MTR, MTRR, and MMADHC genes. Mutations in the MTHFR, MTR, MTRR, and MMADHC genes are rare.

Changes in the CBS gene cause the most common type of homocystinuria. This gene provides instructions for making an enzyme called cystathionine beta-synthase (CBS). Enzymes process the proteins in the body. Certain proteins cannot be broken down when CBS is not working. This is the only gene that is known to cause classic homocystinuria. People with homocystinuria can ask their doctor or genetic counselor about being tested for mutations in the genes that cause homocystinuria. To find a genetic counselor near you, visit the Find a Genetic Counselor tool on the National Society of Genetic Counselors website.

The protein we eat is one of the main sources of an amino acid called methionine. Amino acids are building blocks of proteins. The more protein we eat, the more methionine we have in our body. Methionine is broken down by the body into another amino acid called homocysteine. Enzymes are needed to break down amino acids. In homocystinuria, this amino acid cannot be broken down because the enzyme that is needed is not made correctly. Because the homocysteine cannot be broken down, it builds up in the body. The extra homocysteine causes damage to the body. Dieticians that work in metabolic clinics can help you plan a diet low in protein. To find a metabolic clinic near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

A variant is a change that is found in the gene for homocystinuria, but there is not a lot of information about that change. They can also be called "variants of uncertain significance" or a "VUS". Not all gene changes cause disorders. Some gene changes are normal variations. Sometimes, a variant is a change that has not been seen before in this gene. When this happens, the lab is not sure whether or not this change is part of normal human genetic variation or if it is a change that will cause homocystinuria. A genetic counselor can explain genetic test results and variants. To find a genetic counselor, use the Find a Genetic Counselor Tool on the National Society of Genetic Counselors’ website.

Homocystinuria does not appear to cause problems for the baby during pregnancy. Treatment should be continued during pregnancy. People with homocystinuria are at higher risk for blood clots. These risks may be higher during pregnancy and after delivery. A blood thinner may be prescribed to lower the risk of blood clots. A common blood thinner is Heparin. Aspirin may also be prescribed to reduce the risk of blood clots. Always consult your doctor before taking any medications in pregnancy. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

Body odor is a side effect of betaine. Betaine can cause levels of an amino acid called methionine to increase. Very high methionine levels can cause swelling in the brain (cerebral edema). The side effects reverse when betaine is stopped. Talk to your doctor to learn more about the risk of these side effects. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website.

High levels of homocysteine in the body can lead to many different health problems. There are several forms of homocystinuria. They can be told apart by their signs, symptoms and genetic causes. Symptoms of Homocystinuria can include:

Folate and B12 help change homocysteine back into methionine. This helps lower homocysteine levels in the body. High levels of homocysteine cause the symptoms of homocystinuria. Talk to your doctor to see which medications are right for you. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website.

The symptoms of homocystinuria are can vary a lot from person to person. Some people only have very mild signs of the disorder. Some people may have many health problems. In severe cases, the health problems may be life threatening. There are two types of classic homocystinuria: B6-responsive and B6-non-responsive. B6-responsive is usually milder. B6-non-responsive type can be more severe. Homocysteine levels can be lowered in people with the B6-responsive type when they take vitamin B6 (pyridoxine). The best results for both types are seen in people who are diagnosed early and treated from birth. The severity of symptoms is related to which gene change, or mutation, a person has. It can also be related to their diet or other factors. To find out more about the symptoms of homocystinuria, ask your doctor or a genetic counselor. A genetic counselor near you can be located using the Find a Genetic Counselor Tool on the National Society of Genetic Counselor’s website.

A licensed dietician can help you with a low protein diet. They can make sure that you follow it correctly. Dieticians that work in metabolic clinics have experience with diets needed by people with homocystinuria. To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage. To find a metabolic clinic near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

Homocystinuria can be diagnosed when the levels of two amino acids (the building blocks of proteins) are higher than normal. These amino acids are called homocysteine and methionine. They are measured in a blood sample. Homocysteine levels are also high in the urine. There is not a symptom that is only seen in this disorder. The combination of certain symptoms can be suspicious for the disorder, but are not used for a definite diagnosis. Additional tests are needed. Contact your doctor or a genetic counselor to find out more about the symptoms of homocystinuria. A genetic counselor near you can be located using the Find a Genetic Counselor Tool on the National Society of Genetic Counselor’s website.

Homocystinuria is one of the disorders that can be seen on newborn screening. Newborn screening is done by pricking the heel of the baby. The blood is then blotted on special paper. The levels of certain building blocks of the body (amino acids) are then measured. In homocystinuria, the amino acid methionine is usually measured. If levels are high, then the baby is sent for more testing. This is called testing positive. Testing positive on newborn screening does not mean that the baby has homocystinuria. Additional testing must be done to confirm the disorder. If your baby tests positive for homocystinuria on the newborn screen, talk to your doctor. Your doctor can order other testing to confirm the disorder. They may send you to a special doctor called a medical geneticist. To find a geneticist near you, use the Genetic Services Search Engine on the American College of Medical Genetics website.

Symptoms of homocystinuria can vary from person to person. Some people have a mild form and other people have a severe form. There are two types of classic homocystinuria: B6-responsive and B6-non-responsive. B6-responsive is usually milder. B6-non-responsive type can be more severe. Homocysteine levels can be lowered in people with the B6-responsive type when they take vitamin B6 (pyridoxine). The best results for both types are seen in people who are diagnosed early and treated from birth. A medical geneticist can help arrange for testing and treatment. To find a medical geneticist near you, visit the Genetic Services Search Engine on the America College of Medical Genetics website.

As of May 27, 2016, there are two clinical trials being conducted in the U.S. for homocystinuria. These trials include studies that monitor the effect of medications or that monitor how the disease progresses. To find up to date information on clinical trials, visit www.clinicaltrials.gov and search for homocystinuria. For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:www.centerwatch.com

There is no cure for homocystinuria. Some medications and a special diet can help keep symptoms from getting worse. People with this disorder should eat a special diet. People who are B6-responsive are typically put on a low-protein diet. They will also be given pyridoxine (Vitamin B6) therapy. Pyridoxine helps to lower the levels of harmful products that build up in the body. These products are called methionine and homocysteine. People who are B6-non-responsive are put on a low methionine diet and a low-protein diet. These diets may be missing certain important amino acids (building blocks of the body), so a medical formula is also prescribed to provide what is missing. A medication called Betaine can be used to help keep homocysteine levels low. Vitamin B12 and folate may also be used. These vitamins can help keep homocysteine levels low. Talk to your doctor about available treatments for homocystinuria. Homocystinuria is usually treated by a metabolic geneticist. To find a geneticist near you, use the Genetic Services Search Engine on the American College of Medical Genetics website.

To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

A positive newborn screen does not mean that a baby has homocystinuria. A screening test tells you who is at risk for having the disorder. Babies with homocystinuria have positive screening results. However, healthy babies can also have positive screening results. Healthy babies may have a positive result for many reasons. For example, if the blood sample was too small or was taken too early. Follow up testing is always needed for positive screening tests. Contact your doctor if your baby had a positive newborn screen. Your doctor will arrange for more testing to confirm the disorder. To find a medical geneticist near you, visit the Genetic Services Search Engine on the America College of Medical Genetics website.

Starting a low-protein diet as soon as possible is very important. It will help manage the symptoms of homocystinuria. Seeing a dietician is needed to make sure that the low-protein diet is being managed properly. Follow-up with the patient should include blood work to check levels of an amino acid called homocysteine in the blood. High levels of homocysteine cause the symptoms seen in this disorder. Follow-up for symptoms should be handled as needed. Women should avoid hormonal birth control, as it increases the risk for blood clots. Surgery should be avoided as it increases the risk for blood clots to block a blood vessel. Your doctor can arrange your care with a medical geneticist. They specialize in treating genetic disorders like homocystinuria. You can find a medical geneticist near you by using the Genetic Services Search Engine on the American College of Medical Genetics website. To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

Women with homocystinuria have a greater risk for blood clots. Blood thinners (anticoagulants) are recommended. Blood thinners can lower the risk for blood clots. They should be taken during the third trimester and after delivery. Do not take any medications without talking with your doctor first.

Homocystinuria occurs when a gene called CBS is not working correctly. Everyone has two copies of the CBS gene. You get one copy from your mother and one copy from your father. Homocystinuria occurs when both copies have changes, or mutations. This is called autosomal recessive inheritance. If only one copy of the gene has a change that person is a carrier for homocystinuria. Carriers do not have the disorder. When both parents are carriers:

Some people with homocystinuria improve when taking Vitamin B6 (pyridoxine). If testing shows that someone has the disorder, a pyridoxine test can be done. This is called a pyridoxine challenge. This test is done by measuring certain amino acid levels in the blood to find the usual level. Some amino acid levels are high in homocystinuria. These amino acids are called methionine and homocysteine. After the usual level is measured, the patient is given a dose of pyridoxine. Amino acid levels are then measured again after 24 hours. If they have gotten lower, the patient is a responder. If amino acid levels are still high, then your doctor will give you a higher dose of pyridoxine and remeasure the levels after 24 hours. If you still do not respond, this process is repeated one more time. Talk to your doctor to see if you need this test. To find a medical geneticist near you, visit the Genetic Services Search Engine on the American College of Medical Genetics website.

As of May 27, 2016, The HCU Network Australia is the only professional organization that is taking donations for homocystinuria specifically.

Children Living with Inherited Metabolic Diseases (CLIMB) takes donations from people in the UK for research on inherited metabolic disease.

Testing for homocystinuria is done by performing a physical exam and doing some lab tests. The physical exam is done by a doctor to look for signs and symptoms of the disorder. If the disorder is suspected, additional tests are done. Testing is done by measuring the levels of certain amino acids in the body. Amino acids are the building blocks of proteins. If these amino acid levels are too high, they cause health problems. Urine testing is done to look for high levels of an amino acid called homocysteine. Blood testing is also done to look for high levels of amino acids called homocysteine and methionine. Homocystinuria occurs when the gene for an enzyme called Cystathionine Beta-Synthase (CBS) does not work correctly. A blood test can be done to check for changes in this gene that cause homocystinuria. A skin biopsy may also be performed. In a skin biopsy, a small piece of skin is removed. The activity levels of the CBS enzyme can be measured in these skin cells.

Some people with homocystinuria show improvement when taking Vitamin B6 (pyridoxine). If testing shows that someone has homocystinuria, a pyridoxine test can be done. This is called a pyridoxine challenge. This test is done by measuring amino acid levels in the blood and then giving the patient a dose of pyridoxine. Amino acid levels are then measured again to see if they have gotten lower. If levels have gone down, then the patient is a responder and treatment with pyridoxine is used.

Testing for homocystinuria is usually done by a medical geneticist. To find a medical geneticist in your area, use the Genetic Services Search Engine on the American College of Medical Genetics website.

Metabolic centers usually include a metabolic geneticists, genetic counselors, and a metabolic dietitians experienced in the care of patients with homocystinuria can be in most states in the United States.

To find a genetic professional near you who can discuss genetic testing, visit the following two sites: A listing of medical geneticists can be found at the American College of Medical Geneticists website (www.acmg.net) and genetic counselors can be found on the National Society of Genetic Counselors website: www.nsgc.org. To find a metabolic dietitian specializing in diets for people with metabolic conditions, visit the GMDI Find a Metabolic Dietitian webpage.

The number of people (prevalence) with homocystinuria has been estimated to be between 1 in 200,000 to 1 in 335,000. However, homocystinuria is thought to be more common than these numbers suggest. There are a few populations where homocystinuria occurs much more frequently.

Gene testing for homocystinuria can be done using blood or saliva. Blood is usually used. A skin biopsy may be done to measure the activity level of the cystathionine beta-synthase (CBS) enzyme. Enzyme activity cannot be measured on blood or saliva. Low CBS activity causes homocystinuria. Low enzyme activity causes the build up of certain amino acids in the body. The levels of these amino acids are measured in the blood and urine. Your doctor or a genetic counselor can arrange for testing. To find a genetic counselor near you, use the Find a Genetic Counselor tool on the National Society of Genetic Counselors’ website.

A high protein or high methionine diet can make homocystinuria worse. Foods high in methionine and protein include eggs, cheese, soy, fish, chicken, beef, and dairy. It is important to follow your diet as prescribed by your doctor. A nutritionist can help you develop a diet low in protein.

Carriers are people with only one gene change. Carriers do not have symptoms or show signs of homocystinuria. Carriers are healthy, but have a chance to have an affected child if they partner with another carrier. A genetic counselor can explain the risks to carriers. To find a genetic counselor near you, use the Find a Genetic Counselor tool on the National Society of Genetic Counselors’ website.

Some people with homocystinuria have skeletal defects or eye problems. Surgery may be needed to fix these problems. Care should be taken during surgery in people with this disorder. There is an increased risk of blood clots, which can cause complications. Talk to your doctor to determine your specific treatment needs. Homocystinuria is usually treated by a metabolic geneticist. To find a geneticist near you, use the Genetic Services Search Engine on the American College of Medical Genetics website.

Homocystinuria can also be called classical homocystinuria, homocystinemia, cystathionine beta-synthase deficiency, CBS deficiency, and homocystinuria caused by cystathionine beta-synthase deficiency. To find other names for homocystinuria, check a reliable website such as The National Organization for Rare Diseases.

There are several support groups for homocystinuria.

People with Marfan syndrome can have some of the same symptoms as people with homocystinuria. Some symptoms that can be the same in both disorders are: