General Condition Information
- Homocystinuria (cystathionine beta synthetase)
- Homocystinuria (cystathionine beta-synthase deficiency)
- Homocystinuria (cystathoinine beta synthetase)
- Homocystinuria or variant forms of hypermethioninemia
- The true prevalence of this condition is unknown, but it is estimated that less than 20 babies are born with this condition in the United States each year.
- It is more common in babies of Irish, German, Norwegian, or Qatari descent.
- Visit GeneReviews to learn more about how often this condition occurs.
What is Homocystinuria
Homocystinuria is an inherited (genetic) condition that prevents the body from processing proteins correctly. Your body breaks down the protein that you eat into parts called amino acids. Your body then uses those amino acids to make other proteins that it needs to function.
There are different forms of homocystinuria. All the forms result in high levels of amino acids called methionine or homocysteine in the body.
In the most common form of homocystinuria, you cannot make an enzyme called cystathionine beta-synthase (CBS) correctly. This enzyme uses vitamin B-6 to help change homocysteine into other amino acids that your body needs. This form of the condition is also called “homocystinuria due to CBS deficiency.” There are other, less-common forms of homocystinuria, but they are not well-understood.
There are two types of homocystinuria due to CBS deficiency.
- B-6 responsive homocystinuria: The CBS enzyme is damaged but can still use vitamin B-6 to work.
- B-6 nonresponsive homocystinuria: The CBS enzyme is damaged and cannot use vitamin B-6.
If your baby has any form of homocystinuria, their body has trouble getting rid of homocysteine. This results in a buildup of homocysteine and also methionine, which is made from homocysteine.
High levels of homocysteine and methionine can cause blood clots and damage to the brain and eyes. If untreated, this damage leads to the signs and symptoms of the condition.
Newborn Screening and Follow-Up
Newborn screening for homocystinuria is done using a small amount of blood collected from your baby’s heel. To learn more about this process, visit the Blood Spot Screening page.
During screening, a special machine measures how much of certain amino acids, including methionine and homocysteine, are in your baby’s blood. Amino acids are essential to almost all functions in the body. Babies with high levels of methionine, homocysteine, or both, might have homocystinuria
If your baby’s blood spot screening result for homocystinuria is out-of-range, your baby’s health care provider will contact you. Together, you will discuss next steps and follow-up plans.
An out-of-range screening result does not mean that your baby definitely has the condition. It does mean that your baby needs more follow-up testing. To learn more about screening results, visit the Blood Spot Screening Results page.
Your baby may need the following tests after an out-of-range screening result:
- Blood tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible.
False-positive newborn screening results for this condition are rare. Infants who were born early (premature) or infants on total parenteral nutrition (TPN) may also have out-of-range screening results.
False-negative newborn screening results for this condition can happen. Screening samples collected too early (before the baby is 24 hours old) may affect the results of screening. Some babies with homocystinuria do not have elevated methionine during the first days of life. These babies do not have an out-of-range result even though they have the condition.
Newborn screening helps babies lead healthier lives. If your baby has an out-of-range result, follow up with your health care provider quickly. It is important to follow their instructions. Your baby may need to get treatment right away, even if they are not showing signs or symptoms. In some cases, your baby’s health care provider may decide it is best to watch (monitor) your baby to decide next steps. Careful monitoring and early treatment will help your baby stay as healthy as possible.
Signs of homocystinuria can vary widely and usually start before your baby is 1 year old. Symptoms can result from eating protein-containing foods, including milk, that the body cannot break down or by going long periods without eating. Symptoms can also be brought on by illness or infection. Milder forms of homocystinuria may not appear until later in childhood or adulthood.
Signs of the condition may include the following:
- Poor growth
- Trouble gaining weight
- Nearsightedness (myopia)
- Dislocation of the lens in the eye (ectopia lentis)
- Blood clots
- Tall height and long limbs
- Developmental delay
- Behavioral difficulties
- Learning difficulties
Homocystinuria may be caused by a change in multiple different genes. However, changes in the CBS gene are the most common cause of homocystinuria. The CBS gene gives your body instructions for making the enzyme cystathionine beta-synthase. This enzyme helps process the amino acids homocysteine and methionine.
Without a working CBS gene, the body cannot properly use the amino acid homocysteine. As a result, both homocysteine and methionine build up and become toxic to the body.
- Homocystinuria is an autosomal recessive condition. Babies inherit the condition when each parent passes down a nonworking CBS gene to their baby. Only babies with two nonworking CBS genes—one from the mom and one from the dad—have this condition.
- People with one working copy and one nonworking copy of the CBS gene are called carriers.
- Carriers do not have or develop the condition. However, they may pass down a nonworking copy of the gene to their children.
- If two parents are carriers of a nonworking copy of the CBS gene, they have a 1 in 4 chance of having a child with homocystinuria.
- Carriers for homocystinuria often do not know they are carriers before having a child with the condition. In most cases, families have no history of the condition until the birth of a child with homocystinuria.
- Parents who already have a child with homocystinuria still have a 1 in 4 chance of having another child with homocystinuria. This 1 in 4 chance stays the same for all future children.
- Genetic counselors and medical geneticists can help families learn about this condition and the chance of having children with it. Visit the National Society of Genetic Counselors to find a genetic counselor and the American College of Medical Genetics and Genomics to find a medical geneticist.
Treatment and Management
It is important to talk to your health care provider about which treatment(s) are best for your baby. The goal of treatment is to prevent the health problems caused by this condition.
Treatments may include the following:
- Diet low in protein
- Special formulas and foods
- Vitamin B-6, betaine, folic acid, or other vitamin supplements in some cases of homocystinuria
Children who receive early and ongoing treatment for homocystinuria can have healthy growth and development. Treatment is very important for lowering the chance of blood clots and eye and heart problems. Even with treatment, some children will still have eye problems, but these can be corrected.