General Condition Information
Other Names
- BCKD Deficiency
- Branched-Chain Ketoacid Dehydrogenase Deficiency
- Maple syrup disease
- Maple syrup urine disease (Branched-chain ketoacid dehydrogenase deficiency)
- Maple syrup urine disease (type IA, IB, II)
- Maple syrup urine disorder
Condition Type
Birth Prevalence
- It is estimated that fewer than 30 babies are born with this condition each year in the United States.
- Visit GeneReviews to learn more about how often this condition occurs.
Screening Finding
What is maple syrup urine disease
Maple syrup urine disease is an inherited (genetic) condition that prevents the body from processing proteins correctly. Your body breaks down the protein you eat into parts called amino acids. Your body then uses those amino acids to make other proteins that it needs to function.
Certain enzymes break down a specific type of amino acid called branched-chain amino acids. The branched-chain amino acids are called leucine, isoleucine, and valine.
These enzymes do not work properly in babies with maple syrup urine disease. Either the body does not make enough enzyme or does not produce the enzyme correctly. As a result, babies with maple syrup urine disease have trouble breaking down branched-chain amino acids. Leucine, isoleucine, valine, and other related substances then build up in their body and can be toxic.
There are different types of maple syrup urine disease: classic, intermediate, intermittent, thiamine-response, and unclassified. The form your baby has depends on how well these enzymes work in their body. All forms of this condition can result in sweet-smelling earwax and urine, which is how the condition got its name. The substances the body cannot remove cause this sweet smell.
Without treatment, toxic levels of branched-chain amino acids and their related substances can lead to the signs and symptoms of the condition. In severe cases, this condition can lead to coma or death if not diagnosed and treated early.
Newborn Screening and Follow-Up
Newborn screening for maple syrup urine disease 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 branched-chain amino acids are in your baby’s blood. Babies with high levels of the amino acids leucine, isoleucine, and/or valine might have maple syrup urine disease.
If your baby’s blood spot screening result for maple syrup urine disease 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 and/or urine tests
- Genetic testing using a blood sample
You should complete any recommended follow-up testing as soon as possible. Babies with this condition can have serious health problems soon after birth if they are not diagnosed and treated quickly.
False-positive newborn screening results for this condition can happen. Babies who receive supplemental nutrition, also known as total parenteral nutrition (TPN) or hyperalimentation, may have false-positive screening results for maple syrup urine disease.
Condition Details
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 maple syrup urine disease can vary widely and usually start shortly after birth (1 to 10 days). Symptoms can result from eating foods or milk the body cannot break down or by going long periods without eating. Illness or infection can also bring on symptoms. Milder forms of maple syrup urine disease may not appear until later in childhood or adulthood.
Signs of the condition may include the following:
Maple syrup urine disease is caused by a change in one of three genes: BCKDHA, BCKDHB, or DBT. These genes give your body instructions for making enzymes that form a complex that helps break down branched-chain amino acids.
When the BCKDHA, BCKDHB, or DBT genes are changed, these enzymes do not break down enough isoleucine, leucine, or valine. As a result, these amino acids build up and become toxic to the body.
Maple syrup urine disease is a genetic condition. Babies inherit it from their biological (birth) parents. To learn more about genetic conditions, visit MedlinePlus Genetics.
- Maple syrup urine disease is an autosomal recessive condition. Babies inherit the condition when each parent passes down the same nonworking gene that causes maple syrup urine disease (BCKDHA, BCKDHB, or DBT) to their baby. Only babies with two matching nonworking genes—for example, one nonworking BCKDHA from the mom and one nonworking BCKDHA from the dad—have this condition. Babies with two nonworking genes that do not match—for example, one nonworking BCKDHA from the mom and one nonworking BCKDHB from the dad—will not have this condition.
- People with one working copy and one nonworking copy of the BCKDHA, BCKDHB, or DBT 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 BCKDHA, BCKDHB, or DBT gene, they have a 1 in 4 chance of having a child with maple syrup urine disease.
- Carriers for maple syrup urine disease 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 maple syrup urine disease.
- Parents who already have a child with maple syrup urine disease still have a 1 in 4 chance of having another child with maple syrup urine disease. 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 low protein foods
- Thiamine supplements in some cases
Children who receive early and ongoing treatment for maple syrup urine disease can have healthy growth and development. Some children may still have some symptoms and signs even with early diagnosis and treatment.