What is maple syrup urine disease (MSUD)?

Maple syrup urine disease (MSUD) is a life-threatening metabolic disorder. Metabolic disorders are conditions in which your body can’t function normally because it can’t properly convert food to energy to keep your body healthy.

Protein is needed by the body to function normally. Proteins are made up of 20 different types of amino acids. Proteins must be broken down (metabolized) so they can be absorbed and used by the body. People with MSUD don’t have the needed enzymes (either don’t have the specific enzymes at all, have the specific enzymes but they don’t work, or don’t have enough of the specific enzyme) to break down three particular amino acids – leucine, isoleucine and valine.

Because people with MSUD can’t break down these three amino acids, these amino acids build up in the body, become toxic to the body and cause severe health problems. Without medical management, maple syrup urine disease can lead to a wide range of intellectual and physical disabilities and death.

What are the types of maple syrup urine disease (MSUD)?

The four main types of MSUD are:

• Classic: Classic maple syrup urine disease is the most severe type of MSUD. It is also the most common. Symptoms usually develop within the first three days of birth.
• Intermediate: This type of MSUD is less severe than classic MSUD. Symptoms typically appear in children between the ages of 5 months and 7 years.
• Intermittent: Children with intermittent MSUD develop as expected until an infection or period of stress cause symptoms to appear. People with intermittent MSUD can usually tolerate higher levels of the three amino acids than people with classic MSUD.
• Thiamine-responsive: This type of MSUD responds to treatment using high doses of vitamin B1 (thiamine) along with a restricted diet. With treatment, people with thiamine-responsive MSUD have higher tolerance for the three amino acids.

How common is maple syrup urine disease (MSUD)?

MSUD is very rare. It occurs in about 1 of every 185,000 births worldwide. It appears more often in populations with a small gene pool or when cousins and other close relatives have children together. About 2,000 people in the United States live with MSUD. It affects males and females equally.

Who is affected by maple syrup urine disease (MSUD)?

MSUD can affect anyone, but people whose parents are closely related are much more likely to have the metabolic disease. For this reason, MSUD frequently occurs among Mennonites in the United States, where members of the community often marry each other. MSUD occurs in 1 of every 380 births in the Mennonite population.

How do people get maple syrup urine disease (MSUD)?

MSUD is inherited (passed on) through families. A child is born with MSUD when both parents are carriers of three specific gene mutations (changes) and their child inherits copies of these altered genes – one copy from each parent. These mutations result in little to no activity of enzymes needed to break down three specific amino acids that are in protein-rich foods. These three specific amino acids are leucine, isoleucine and valine. Without the needed enzymes, the three amino acids build up and so do their toxic byproducts (called ketoacids). This leads to the serious health problems seen in MSUD.

MSUD occurs more often in communities that have little genetic variation (such as the Mennonite community in the United States). These groups have a higher concentration of people who are carriers of the mutated gene.

What are the symptoms of maple syrup urine disease (MSUD)?

Symptoms of classic MSUD appear in newborns within 48 hours of birth. In older children, signs of intermediate, intermittent, and thiamine-responsive MSUD usually develop before age seven. All four types of MSUD have symptoms including:

• Urine, sweat, or earwax that smells like maple syrup or burnt sugar. (This disorder got its name from this common symptom.) This may not always be present in all types.
• Poor feeding, vomiting, loss of appetite, irritability.
• Sluggish/slow/tiredness and weakness.
• Changes in muscle tone – poor muscle tone, muscle tightness/tension
• Abnormal muscle movements, spasms that cause a backward arching of the head, neck and spine.
• Developmental delay.
• Seizures, convulsions, respiratory failure and coma (as the condition progresses).

How is maple syrup urine disease (MSUD) diagnosed?

Doctors diagnose classic MSUD with newborn screenings (blood tests) soon after a baby is born. People with intermediate, intermittent, or thiamine-responsive MSUD might not show signs of the disease until their toddler years or early childhood. In these cases, doctors diagnose MSUD with blood tests and by evaluating the child’s symptoms, including finding the distinctive sugar/maple smell of their sweat and urine. Genetic testing from white cells in blood can now help confirm diagnosis and also help identify types of MSUD.

How do I know if my child has maple syrup urine disease (MSUD)?

If your baby or child has urine or sweat that smells sweet, you should call 911 or go directly to the emergency room. Other signs include being weak or sluggish/tired or having a sudden decrease in appetite. Only a doctor can diagnose maple syrup urine disease.

What are the treatments for maple syrup urine disease (MSUD)?

Doctors can manage MSUD by controlling the level of the three amino acids (leucine, isoleucine and valine) in the patient’s body. People with MSUD must always follow a strict diet that provides essential nutrients but severely limits the amounts of the three amino acids (people do need a small amount of the three amino acids for normal growth and development). Thiamine-responsive MSUD can be managed with high doses of vitamin B1 (thiamine) and a strict diet.

Doctors monitor people with MSUD throughout their lives to make sure the three amino acids do not exceed a person’s tolerance level and begin to cause harm. When patients with MSUD get sick, have fever, cannot keep food down due to vomiting or diarrhea or when amino acids rise to dangerous levels, the patient must be hospitalized immediately. In the hospital, doctors may:

• Give glucose and insulin through a vein (using an IV) to adjust the level of amino acids in the body.
• Use an IV or nasogastric feeding tube (through the nose) to deliver particular nutrients, including the types of amino acids the person can tolerate.
• Filter the person’s blood plasma and return it to their body (a procedure called hemofiltration/dialysis) to lower the level of the three amino acids.
• Monitor the patient for signs of brain swelling or infection and acid buildup.

Is there a permanent treatment for maple syrup urine disease (MSUD)?

Since 2004, liver transplants have been very successful in treating individuals with classic MSUD. With a new liver, people with MSUD can produce the enzymes they need to break down the three amino acids that build up in body. After a liver transplant, people with MSUD can eat an unrestricted diet, live without symptoms, and avoid further cognitive problems. People with MSUD still carry the gene for the disorder and therefore can still pass it to their offspring. Genetic counseling is recommended.

What are the side effects of the treatment for maple syrup urine disease (MSUD)?

Side effects of IV glucose and insulin include changes in blood sugar levels. Doctors will monitor these levels closely in the hospital to ensure they remain in the normal range.

Side effects of hemodialysis and hemofiltration include muscle cramps, low blood pressure (hypotension) and changes in blood electrolyte contents that will need close monitoring.

A liver transplant includes complications similar to any surgical procedure, including bleeding, infection, and blood clots. Transplantation also brings other potential complications, including organ rejection and a weakened immune system (beyond what is needed to prevent organ rejection). With improved understanding of the transplant process, patients can lead normal lives with good monitoring and without the fear of problems related to MSUD.

What are the complications associated with maple syrup urine disease (MSUD)?

People with MSUD can develop a variety of complications ranging from mild to severe. Complications of maple syrup urine disease include:

• Brain damage, neurological problems, and developmental delays.
• Increased risk of attention deficit/hyperactivity disorder (ADHD), anxiety, and depression.
• Loss of bone mass, causing bones to fracture easily.
• Swelling of the pancreas/pancreatitis, especially during crisis states.
• Chronic headaches caused by an increase in blood pressure in the skull.
• Movement disorders such as tremors and uncontrolled muscle contractions.
• Coma and death that arise from crisis states such as infection, stress or poor dietary control.

How can you prevent maple syrup urine disease (MSUD)?

There is no way to prevent maple syrup urine disease. You can lower your risk of having a baby with MSUD by ensuring that your partner is not related to you. If you have siblings or other relatives with MSUD, you should talk to your doctor before becoming pregnant to discuss the possibility of passing the disease to your child. Your doctor may test you and your partner to see if you are carriers for the gene that causes MSUD.

What can I do to help relieve symptoms of maple syrup urine disease (MSUD)?

If your child has symptoms of MSUD, you should not try to care for them at home. Call 911 or go directly to the emergency room.

What is the outlook for patients who have maple syrup urine disease (MSUD)?

People with MSUD can grow into adulthood by following a strict diet and avoiding illness and stress as much as they can. While it is possible to manage the disorder with a protein-restricted diet and close medical supervision, people with MSUD are always at risk of having a metabolic attack. Symptoms can suddenly return at any time, usually after the person:

• Gets an infection.
• Doesn’t eat for an extended time (fasts).
• Experiences trauma or stress (either physical or psychological).
• Has a change in diet or doesn’t follow the recommended diet.

When a metabolic attack occurs, people with MSUD must seek medical attention right away. Immediate care can reduce the risk of brain damage and other complications. Talk with your doctor about the possibility of a liver transplantation.

When should I call my doctor about maple syrup urine disease (MSUD)?

If your baby or child shows signs of MSUD, you should seek immediate medical care. Though it is very rare for older children and adults to develop the disease, you should contact your doctor any time you detect a maple syrup smell in urine or sweat.