Conditions Maple Syrup Urine Disease

Maple syrup urine disease (MSUD) is a condition in which the body is unable to break down certain proteins. The condition is named for the sweet odor of the urine of untreated babies. MSUD is considered an amino acid condition because people with MSUD have trouble breaking down certain amino acids, the building blocks of proteins. Detecting MSUD early and beginning treatment can often prevent the severe outcomes of the condition.

Condition Type

Amino Acid Disorders

Frequency

Maple syrup urine disease (MSUD) affects one out of every 185,000 babies born worldwide. It is found in many countries throughout the world, although the condition is more common in certain ethnic groups. About one out of every 380 babies from the Old Order Mennonite population is affected by the condition. MSUD is also more common in people of French-Canadian ancestry and Ashkenazi Jewish ancestry.

Also known as

  • MSUD
  • Branched-chain alpha-keto acid dehydrogenase deficiency
  • Branched-chain ketoaciduria
  • Ketoacidemia
  • BCKD deficiency

Follow-Up Testing

Your baby’s doctor may ask you if your baby is showing any of the signs of MSUD (see Early Signs, below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.

If your baby’s newborn screening result for maple syrup urine disease (MSUD) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your baby to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated MSUD can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.

Follow-up testing will involve checking your baby’s urine and blood samples for harmful amounts of acids and toxins. Certain acids and toxins build up in the body when a child has an amino acid condition, so measuring the amounts of these substances in your baby’s body can help doctors determine if your baby has a condition. High amounts of branch-chained amino acids in the blood and ketones in the urine might indicate that your baby has MSUD.

About Maple Syrup Urine Disease

Early Signs

Forms of maple syrup urine disease (MSUD) vary widely in the severity of their signs. “Classic MSUD” is the most common form and is seen in babies.

Babies with classic MSUD usually begin showing signs shortly after birth. These signs include:

  • Poor appetite
  • Trouble sucking during feeding
  • Weight loss
  • High pitched cry
  • Urine that smells sweet like maple syrup or burnt sugar
  • Sleeping longer or more often
  • Tiredness
  • Irritability
  • Vomiting
  • Developmental delays

Many of these signs may occur when your baby eats foods that his or her body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.

If your baby shows any of these signs, be sure to contact your baby’s doctor immediately.

Treatment

Dietary Treatments

Your baby may need to be on a protein-restricted diet to avoid foods containing proteins that your baby’s body cannot break down. A dietician can help you plan the best diet for your child. Special formulas and foods for children with maple syrup urine disease (MSUD) are also available. These formulas will likely need to continue through adulthood.

Supplements and Medications

Thiamine supplements are helpful for some children with MSUD. Your baby’s doctor will be able to determine if your baby has a type of MSUD that is considered “thiamine-responsive” and write an appropriate prescription.

Expected Outcomes

If maple syrup urine disease (MSUD) is treated early, children can have healthy growth and development.

Some children may still experience signs of MSUD even with treatment.

It is important to treat MSUD because babies who do not receive treatment are at risk for brain damage, coma, or death.

Causes

When we eat food, enzymes help break it down. Some enzymes break down proteins into their building blocks, called amino acids. Other enzymes break down the amino acids. In maple syrup urine disease (MSUD), the group of enzymes called branched-chain ketoacid dehydrogenase (BCKAD) complex is not working correctly.

BCKAD is a group of four enzymes that work together to break down the amino acids leucine, isoleucine, and valine for energy. You may hear these called the branched-chain amino acids. These three amino acids all share a similar branched shape.

If your baby has MSUD, then his or her body is lacking one or more of the enzymes in the BCKAD complex. This causes the BCKAD group not to work correctly. When BCKAD is not working, your baby’s body cannot break down the branched chain amino acids. The amino acids then build up in the blood. High levels of these amino acids in the blood can be toxic.

MSUD is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for MSUD, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with MSUD is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.

Support for Maple Syrup Urine Disease

Support Services

Support groups can help connect families who have a child or other family member affected with maple syrup urine disease with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.

Accessing Care

Work with your baby’s doctor to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with a physician who specializes in metabolism, a dietician who can help plan your child’s specialized diet, and other medical resources in your community. Some children with maple syrup urine disease (MSUD) have developmental delays. If you think that your baby is not meeting his or her developmental milestones, ask your baby's health care provider about the next steps in accessing a developmental evaluation and care.

Because MSUD is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for MSUD, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the American College of Medical Genetics and Genomics (ACMG) and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.

Families' Experiences

Connor was diagnosed with maple syrup urine disease (MSUD) through newborn screening. Thanks to early treatment, Connor is healthy and very active in sports. Read Connor’s story on the MSUD Family Support Group website.

Read other stories of families from all over the world who are affected by MSUD on the MSUD Family Support Group website.

Six children in the Burkholder family have MSUD. While the Burkholder’s first child did not have the benefit of an early diagnosis through newborn screening, their other children did. This large Mennonite family from Pennsylvania shares their experience with MSUD in the online version of the MSUD Family Support Group newsletter.

Courtney wrote her story of living with MSUD when she was eight-years-old. Learn about MSUD from the point of view of a child living with it.

References & Sources

Visit MedlinePlus Genetics for more condition information

Visit the Screening, Technology And Research in Genetics (STAR-G) Project for more information on MSUD

Visit GeneReviews for more information on maple syrup urine disease

ACT Sheets

Healthcare professionals can learn more about confirmatory testing by reading the American College of Medical Genetics and Genomics' Algorithm for Diagnosis and ACT Sheet, a guide for follow-up after newborn screening. You can visit this page of the ACMG website here.

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