People with maple syrup urine disease (MSUD) can’t break down three specific amino acids found in protein-containing foods. These amino acids build up, become toxic and cause severe health problems. Without medical management, MSUD can lead to a wide range of intellectual and physical disabilities. It can be fatal without proper management.
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:
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.
The four main types of MSUD are:
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).
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services. Policy
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:
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:
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.
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,
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:
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).
The toxins in your system can damage several organs and body systems. Complications include:
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.
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.
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:
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.
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.
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:
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.
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.
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.
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.
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.
A note from Cleveland Clinic
Most of us think of maple syrup as a pleasant smell, but when it comes to maple syrup urine disease, that sweet, sugary scent is a warning sign to seek care fast. Get your child to an ED immediately if you notice signs of MSUD or a metabolic crisis. Taking fast action can prevent complications and save your child’s life. If you’re living with an MSUD diagnosis, take care to follow your nutritionist’s guidance on a meal plan that’s healthy and safe. And know the signs of a metabolic crisis so you can get help immediately if too many amino acids build up in your body.
Last reviewed by a Cleveland Clinic medical professional on 09/25/2023.
Learn more about our editorial process.