Children and Youth with Special Health Needs (CYSHN)

Maple Syrup Urine Disease (MSUD)

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Condition Information

Treatment Options: Taking Action

Family Support Resources

CONDITION INFORMATION

This fact sheet has general information about MSUD. Every child is different and some of these facts may not apply to your child specifically. Certain treatments may be recommended for some children but not others. Children with MSUD should be followed by a metabolic doctor in addition to their primary doctor.

What is MSUD?

MSUD stands for “maple syrup urine disease.” It is named for the sweet maple syrup smell of the urine in untreated babies. MSUD is one type of amino acid disorder. People with this condition have problems breaking down certain amino acids found in protein.

Amino Acid Disorders:

Amino acid disorders (AAs) are a group of rare inherited conditions. They are caused by enzymes that do not work properly.

Protein is made up of smaller building blocks called amino acids. A number of different enzymes are needed to process these amino acids for use by the body. Because of missing or non-working enzymes, people with amino acid disorders cannot process certain amino acids. These amino acids, along with other toxic substances, then build up in the body and cause problems.

The symptoms and treatment vary between different amino acid disorders.

They can also vary from person to person with the same amino acid disorder. See the fact sheets for each specific amino acid disorder.

Amino acid disorders are inherited in an autosomal recessive manner and affect both males and females.

What causes MSUD?

They can also vary from person to person with the same amino acid disorder. See the fact sheets for each specific amino acid disorder.

Amino acid disorders are inherited in an autosomal recessive manner and affect both males and females.

MSUD Diagram

Leucine, isoleucine, and valine are called “branched-chain amino acids” (BCAAs) because of their “tree-like” structure. They are found in all foods that contain protein. Large amounts are found in meat, eggs, milk, and other dairy foods. Smaller amounts are found in flour, cereal, and in some vegetables and fruits.

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What causes the BCKAD enzymes to be absent or not working correctly?

Genes tell the body to make various enzymes. People with MSUD have a pair of genes that do not work correctly. Because of the changes in this pair of genes, the BCKAD enzymes either do not work properly or are not made at all.

How is MSUD inherited?

MSUD is inherited in an autosomal recessive manner. It affects both boys and girls equally.

In children with MSUD, a pair of genes needed to make the BCKAD enzymes is not working correctly. These children inherit one non-working gene for the condition from each parent.

Parents of children with MSUD rarely have the disorder. Instead, each parent has a single non-working gene for MSUD. They are called carriers. Carriers do not have the condition because the other gene of this pair is working correctly.

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have MSUD. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.

Autosomal Recessive Inheritance chart

When both parents are carriers, there is a 25% chance in each pregnancy for the child to have MSUD. There is a 50% chance for the child to be a carrier, just like the parents. And, there is a 25% chance for the child to have two working genes.

Is genetic testing available?

Genetic testing for MSUD can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes in the pair of genes that cause the condition.

DNA testing is not necessary to diagnose your child. However, it can be helpful for carrier testing or prenatal diagnosis, discussed below.

What other testing is available?

MSUD can be confirmed by measuring the amount of the branched chain amino acids in a blood sample. It can also be diagnosed by an enzyme test using a blood or skin sample. Talk to your doctor or genetic counselor if you have questions about testing for MSUD.

Can you test during pregnancy?

If both gene changes have been found in the child with MSUD, DNA testing can be done during future pregnancies. The sample needed for this test is obtained by either CVS or amniocentesis. CVS stands for Chorionic Villus Sampling, which is a special test done early in pregnancy. During CVS, a small sample of the placenta is removed for genetic testing.

If DNA testing would not be helpful, an enzyme test can be done on cells from the fetus. Again, the sample needed for this test is obtained by either CVS or amniocentesis.

Parents may choose to have testing during pregnancy or wait until birth to have the baby tested. A genetic counselor can talk to you about your choices and answer questions about prenatal testing or testing your baby after birth.

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Can other members of the family have MSUD or be carriers?

Having MSUD
If they are healthy and growing normally, older brothers and sisters of a baby with MSUD are unlikely to have the condition. If you have questions about testing your other children, talk with your metabolic doctor or genetic counselor.

MSUD Carriers
Brothers and sisters who do not have MSUD still have a chance to be carriers like their parents. Except in special cases, carrier testing should only be done in people over 18 years of age.

Each of the parents' brothers and sisters has a 50% chance to be a carrier. It is important for other family members to be told that they could be carriers. There is a small chance they are also at risk to have children with MSUD.

When both parents are carriers, newborn screening results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening. It is very important that this testing be done shortly – ideally at 24 hours of age.

Can other family members be tested?

Diagnostic testing
When both parents are carriers, newborn screening results are not sufficient to rule out the condition in a newborn baby. In this case, special diagnostic testing should be done in addition to newborn screening. It is very important that this testing be done shortly – ideally at 24 hours of age.

Carrier testing
If both gene changes have been found in your child, other family members can have DNA testing to see if they are carriers.

If DNA testing is not helpful, other methods of carrier testing may be available. If you have questions about carrier testing, ask your genetic counselor or metabolic doctor.

How many people have MSUD?

If DNA testing is not helpful, other methods of carrier testing may be available. If you have questions about carrier testing, ask your genetic counselor or metabolic doctor.

Does MSUD happen more frequently in a certain ethnic group?

MSUD occurs in all ethnic groups. It is more common in Mennonite people in certain parts of the United States. In the U.S., about one in 380 babies of Mennonite background is born with MSUD. It is also more common in people of French-Canadian ancestry.

Does MSUD go by any other names?

MSUD is sometimes also called:

  • branched chain ketoaciduria
  • branched chain alpha-keto dehydrogenase deficiency
  • BDKD deficiency
  • Maple Syrup Disease
  • Branched Chain Ketoacid Dehydrogenase deficiency
  • BCKD deficiency

There are a number of other forms of MSUD that are less common than the classic type. These other forms are not discussed in this fact sheet.

  • Intermittent branched-chain ketoaciduria
  • Intermediate branched-chain ketoaciduria
  • Thiamine responsive MSUD
  • MSUD Type 1B
  • MSUD Type II

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TREATMENT OPTIONS: TAKING ACTION

What is the treatment for MSUD?

Your baby's primary doctor will work with a metabolic doctor and a dietician to care for your child.

Prompt treatment is needed to prevent mental retardation and serious medical problems. Most children need to eat a very low-protein diet and drink a special medical formula. You should start the diet and the formula as soon as you know your child has MSUD. Your dietician can create a food plan that contains the right amount of protein, nutrients, and energy to keep your child healthy.

The following are treatments often recommended for children with MSUD:

1.

Medical Formula
In addition to a low-protein diet, children are often given a special medical formula as a substitute for milk. This formula gives them the nutrients and protein they need while helping keep their BCAA levels in a safe range.

Your metabolic doctor and dietician will tell you what type of formula is best and how much to use.
2.

Diet low in branched-chain amino acids
The diet is made up of foods that are very low in the BCAAs. This means your child will need to avoid foods such as cow's milk, regular formula, meat, fish, cheese and eggs. Regular flour, dried beans, nuts, and peanut butter also have BCAAs and must be avoided or strictly limited.

Many vegetables and fruits have only small amounts of the BCAAs and can be eaten in carefully measured amounts.

There are other medical foods such as special low-protein flours, pastas, and rice that are made especially for people with MSUD. Some states offer help with payment, or require private insurance coverage for medical formula and other special medical foods.

Your metabolic doctor and dietician will decide on the best food plan for your child. The exact plan will depend on many things such as your child's age, weight, and general health. Your dietician will fine-tune the diet over time. Any diet changes should be made under the guidance of a dietician.

Lifelong treatment with the MSUD diet is necessary. Children are at risk for episodes of metabolic crisis when they don‟t follow the diet.
3. Supplements
Children with a rare form of MSUD, called “thiamine-responsive MSUD”, can often be helped by thiamine supplements. Some children with classic MSUD may also benefit from thiamine. Ask your doctor whether your child should take thiamine supplements. Do not use any supplements without checking with your doctor.
4. Tracking BCAA levels
Your child will have regular blood tests to measure amino acid levels. The diet and formula may need to be adjusted based on blood test results.
5.

Call your doctor at the start of any illness
For children with MSUD, even minor illness can cause a metabolic crisis. In order to prevent problems, call your doctor right away when your child has any of the following:

  • poor appetite
  • low energy or extreme sleepiness
  • vomiting
  • an infection or illness
  • a fever
  • behavior or personality changes
  • difficulty walking or balance problems

Children with MSUD need to eat more carbohydrates and drink more fluids during any illness – even if they're not hungry – or they could have a metabolic crisis. Children who are sick may not want to eat. If they can't eat, or if they show signs of a metabolic crisis, they may need to be treated in the hospital.

Ask your metabolic doctor if you should carry a special travel letter with medical instructions for your child's care.
6.

Liver transplantation
Liver transplant surgery is an optional treatment for people with MSUD. The BCKAD enzyme that causes MSUD is located in the liver. Because of this, some children with MSUD have had liver transplantation surgery (removal of their liver and replacement with a donor liver) to treat their MSUD symptoms.

This major surgical procedure is associated with risks, and individuals who have had a liver transplant must take medication for the rest of their lives to prevent their body from rejecting the donor liver. However, successful liver transplantation cures people of their MSUD symptoms.

Many factors must be considered before surgery and this option should be discussed very thoroughly with your child‟s physicians.

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What happens when MSUD is treated?

With prompt and lifelong treatment, children with MSUD often have healthy lives with typical growth and development. Early treatment can help prevent brain damage and mental retardation.

Even with treatment, some children still develop swelling of the brain or have episodes of metabolic crisis. Children who have repeated metabolic crises may develop permanent brain damage. This can cause lifelong learning problems, mental retardation or spasticity.

If MSUD is not treated, what problems occur?

There are a number of different forms of MSUD. The most common form, “classic MSUD”, can be life-threatening and must be treated promptly to prevent serious health problems. Other forms, including „intermediate‟ and „intermittent‟ forms of MSUD, are less severe. These milder forms are less common. This fact sheet contains information on classic MSUD..

Classic MSUD
Symptoms start as soon as a baby is fed protein, usually shortly after birth. Some of the first symptoms are:

  • poor appetite
  • weak suck
  • weight loss
  • high pitched cry
  • urine that smells like maple syrup or burnt sugar

Babies with MSUD have episodes of illness called metabolic crisis. Some of the first symptoms of a metabolic crisis are:

  • extreme sleepiness
  • sluggishness
  • irritable mood
  • vomiting

If not treated, other symptoms can follow:

  • episodes where muscles tone alternates between being rigid and floppy
  • swelling of the brain
  • seizures
  • high levels of acidic substances in the blood, called metabolic acidosis
  • coma, sometimes leading to death

Symptoms of a metabolic crisis often happen:

  • after going too long without food
  • during illness or infection
  • during stressful events such as surgery

Without treatment, brain damage can occur. This can cause mental retardation or spasticity. Some babies become blind. If not treated, most babies die within a few months.

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FAMILY SUPPORT RESOURCES

Where can I find more information?

Minnesota Pediatric Metabolic Providers List

Medically Prescribed Formula: a table that provides a list of commonly prescribed medical foods and formulas and /or medication for this disorder.

The MSUD Family Support Group
http://www.msud-support.org/

CLIMB (Children Living with Inherited Metabolic Disorders)
http://www.climb.org.uk

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For additional genetics information and resources:

More help available from Children and Youth with Special Health Needs (CYSHN):

We would like to acknowledge the Star G Project. The information on the fact sheet was obtained from the Star G Project. For the most up-to-date information on the disorder please visit their web site at http://www.newbornscreening.info. Each fact sheet was extensively reviewed by family support groups, metabolic specialists across the country and the Star G steering committee.

THIS INFORMATION DOES NOT PROVIDE MEDICAL ADVICE. All content, including text, graphics, images and information are for general informational purposes only. You are encouraged to confer with your doctor or other health care professional with regard to information contained on this information sheet. After reading this information sheet, you are encouraged to review the information carefully with your doctor or other healthcare provider. The Content is not intended to be a substitute for professional medical advice, diagnosis or treatment. NEVER DISREGARD PROFESSIONAL MEDICAL ADVICE, OR DELAY IN SEEKING IT, BECAUSE OF SOMETHING YOU HAVE READ ON THIS INFORMATION SHEET.
Updated Wednesday, 25-Jul-2012 16:46:47 CDT