Maple Syrup Urine Disease

What is maple syrup urine disease (MSUD)?

Maple syrup urine disease (MSUD) is a lifelong and potentially life-threatening inherited metabolic disorder. Metabolic disorders cause problems with how your body breaks down food into the tiny components it uses for energy. With MSUD, your body has trouble breaking down amino acids, the building blocks of protein. People with MSUD have trouble breaking down three amino acids in particular:

• Leucine.
• Isoleucine.
• Valine.

If you’re born with maple syrup urine disease, these amino acids can build up and become toxic (poisonous) in your body. The buildup causes the telltale sign of MSUD, urine (pee), earwax or sweat that smells like maple syrup or burnt sugar.

Seek immediate treatment if you see signs of MSUD in your child. Without prompt care, MSUD can cause serious complications, including developmental delays and even death.

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. It’s 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 5 months and 7 years old.
• Intermittent: Children with intermittent MSUD develop as expected until an infection or period of stress causes symptoms to appear. People with intermittent MSUD usually tolerate higher levels of the three amino acids than those 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 a higher tolerance for the three amino acids.

How common is maple syrup urine disease (MSUD)?

MSUD is very rare. It affects about 1 in every 185,000 babies born worldwide.

It occurs more often in populations with a small gene pool or when close relatives have children together. For example, MSUD is more common among Mennonites in the United States (1 in every 380 births), where community members often marry and have kids. It’s also more common in the Ashkenazi Jewish population (1 in every 26,000 births).

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 7. Symptoms can progress from mild to potentially life-threatening without treatment. Getting your child to an emergency department (ED) immediately at the first sign of MSUD is essential.

Signs that your child has MSUD include:

• A sweet, syrupy smell in their pee, sweat or earwax.
• Lethargy (they may move slowly or appear tired or weak).
• Irritability or fussiness.
• Not eating.

Without treatment, symptoms can progress to a metabolic crisis. During a metabolic crisis, the processes that allow your body to break down food malfunction. The amino acids and toxic byproducts they produce build up in your body.

Signs of a metabolic crisis include:

• Abnormal muscle movements (spasms causing your child to arch their head, neck and spine backward).
• Seizures or convulsions (uncontrollable shaking).
• Vomiting.
• Coma.

Without treatment, a metabolic crisis can lead to death.

Even diagnosed children and adults managing MSUD can experience trigger events — like an infection, injury and stress — that cause a metabolic crisis. Get help fast.

What causes maple syrup urine disease (MSUD)?

Children born with MSUD inherit a genetic mutation that prevents their bodies from breaking down the amino acids leucine, isoleucine and valine. Normal (non-mutated) genes contain instructions that tell your body how to make enzymes (chemicals) that break down these amino acids. But if you have the mutations, you may have little to none of the enzyme activity needed to break down these amino acids. For example,

• Your body may not make the enzymes at all.
• Your body may not make enough of the enzymes.
• Your body may make enough enzymes — but they don’t work correctly to break down the amino acids.

As a result, the amino acids build up, and so do their toxic byproducts. This leads to a metabolic crisis.

The mutations may appear on any of the three genes responsible for enzymes breaking down the three amino acids. These genes are:

• BCKDHA.
• BCKDHB.
• DBT.

How is maple syrup urine disease (MSUD) inherited?

It’s inherited in an autosomal recessive pattern. A child is born with MSUD when both parents are carriers of the specific gene mutation and pass it on. Being a “carrier” means you have one normal copy of the gene and one mutated copy. Carriers don’t develop MSUD. To develop MSUD, you inherit two mutated genes — one copy of the altered gene from each parent.

The way you inherit MSUD is what causes it to be more common in communities where people share similar genes (and similar genetic mutations).

What are the complications of this condition?

The toxins in your system can damage several organs and body systems. Complications include:

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

How is maple syrup urine disease (MSUD) diagnosed?

Healthcare providers diagnose classic MSUD with newborn screenings (blood tests) soon after a baby is born. Prenatal testing can show if the fetus has classic MSUD. Depending on how far along you are in your pregnancy, providers test a tissue sample from the placenta (chorionic villus sampling) or amniotic fluid (amniocentesis).

Children with intermediate, intermittent, or thiamine-responsive MSUD might not show signs of the disease until their toddler years or early childhood. In these cases, providers diagnose MSUD with metabolic blood tests and genetic testing. Evaluating your child’s symptoms (recognizing the distinctive sugar/maple smell of their sweat, urine or earwax) may give clues to the diagnosis.

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

Healthcare providers manage MSUD by controlling the level of the three amino acids (leucine, isoleucine and valine) in your body and providing emergency treatment to reverse a metabolic crisis if one arises.

Diet

You or your child will need to follow a strict diet that provides essential nutrients but limits the amounts of the three amino acids. This means you’ll need to limit your protein. Everyone needs a small amount of these amino acids for growth and development. But too many acids can lead to a metabolic crisis. You’ll work with a nutritionist to determine a safe and healthy diet.

For example, you may need to limit your intake of:

• Meat products, like beef, pork, fish or chicken.
• Dairy products, like milk, eggs and cheese.
• Legumes, like nuts, chickpeas or beans.

If you’re feeding a newborn with classic MSUD, you’ll need to use a formula rich in essential nutrients but lacking the three amino acids.

Your nutrition intake may need to include supplements of isoleucine and valine to make up for what you’re not getting in food. High doses of vitamin B1 (thiamine) and a strict diet can manage thiamine-responsive MSUD.

Monitoring

If you have MSUD, your healthcare providers will monitor you throughout your life to make sure the three amino acids don’t exceed your tolerance level. You’ll need frequent blood and urine tests to check your levels. Your provider can recommend diet adjustments based on your test results.

Emergency care for metabolic crises

You’ll need to get to a hospital immediately if you’re experiencing symptoms of a metabolic crisis. In the hospital, your care team may:

• Give glucose (10% dextrose) and insulin through a vein (using an IV) to adjust the level of amino acids in your body.
• Use an IV or nasogastric feeding tube (through your nose) to deliver particular nutrients, including the types of amino acids you can tolerate.
• Filter your blood plasma and return it to your body (a procedure called hemodialysis) to lower the level of the three amino acids.
• Monitor you for signs of brain swelling or infection and acid buildup, and provide treatment as needed.

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

Since 2004, liver transplants have successfully treated people with classic MSUD. A new liver can produce the enzymes needed to break down the three amino acids. After a liver transplant, you can eat an unrestricted diet, live without symptoms, and avoid further symptoms or complications.

But you’ll still carry the gene for MSUD, which means you can pass it on to your child. See a genetic counselor before trying for a baby.

What are the side effects of a liver transplant for maple syrup urine disease (MSUD)?

A liver transplant includes complications like any surgery, including bleeding, infection and blood clots. A liver transplant also has other potential complications, including organ rejection and a weakened immune system. For example, you’ll need to take medicines called immunosuppressants, so your body doesn’t reject your liver. These medicines calm your immune system response and can make it harder for your body to fight infections.

Still, many people with MSUD who get a liver transplant go on to lead normal lives without fearing problems related to MSUD.

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

You can’t prevent maple syrup urine disease. You can lower your risk of having a baby with MSUD by ensuring that you and your partner don’t carry the gene mutations for MSUD. The best way to prevent this is by choosing partners who don’t share similar DNA.

If you have siblings or other relatives with MSUD, you should talk to your healthcare provider before becoming pregnant to discuss the possibility of passing the disease to your child. Your provider may test you and your partner to see if you’re carriers for the gene that causes MSUD.

What is the outlook for people with maple syrup urine disease (MSUD)?

Children with MSUD can grow into healthy adults by following a strict diet and avoiding illness and stress as much as they can. It’s possible to manage the disorder with a protein-restricted diet and close medical supervision, but people with MSUD are always at risk of having a metabolic crisis.

You have a better chance of living a normal life with an average life expectancy if you receive treatment before (or soon after) first experiencing symptoms.

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’s very rare for older children and adults to develop the disease, you should contact your provider any time you detect a maple syrup smell in urine or sweat.