Maple syrup urine disease (MSUD) is a rare inherited disease that causes the urine to have a characteristic maple syrup smell. Without treatment, it can lead to potentially life threatening complications.
MSUD is a condition where the body does not process certain amino acids. When this occurs, an abnormal buildup of toxins in the blood occurs.
This article reviews MSUD, including its types, symptoms, causes, and more.
MSUD is a rare disease. It is estimated to affect less than 5,000 people in the United States.
Typically, the body breaks down protein foods into amino acids and removes any excess amino acids. However, those with MSUD lack the enzyme activity needed to break down three types of amino acids present in all protein foods.
The inability to process these proteins causes a buildup of toxins in the blood. Without treatment, this can lead to several symptoms and potentially fatal complications.
Types
There are four main types of MSUD, which
| Description | Enzyme activity | |
|---|---|---|
| Classic | This is the most common form, and people will need to eat a diet that is very low in protein. Without treatment, or if treatment lapses, a person can develop potentially life threatening complications. | 0–2% |
| Intermediate | Though a person can tolerate a bit more protein in their diet, they can lapse during periods of illness. During a lapse in treatment or during a crisis, the symptoms and risks are similar to those in the classic form. | 3–30% |
| Intermittent | A person with intermittent MSUC can often tolerate normal levels of protein. When a crisis occurs, symptoms and complications can be severe. | 5–20% |
| Thiamine-responsive | A distinct form of MSUD, people with this type will typically respond well to large doses of thiamine. People with this type can have some protein in their diet. The ability to treat the condition with thiamine can make it easier for doctors to manage. | 2–40% |
Symptom severity can range from mild to severe. The amount of enzyme activity may influence the severity of symptoms.
Classic MSUC
Signs of classic MSUD typically appear 24–48 hours after birth, and can include:
- a maple syrup smell in the urine
- weight loss
- poor feeding
- vomiting
- irritability
- a tense, arched posture
- lack of energy
- seizures
- muscle tone that changes between limp and stiff
- fluid collection in the brain
Those with MSUD may also experience metabolic crisis. Symptoms can include:
- vomiting
- lack of energy
- breathing difficulties
- irritability
A metabolic crisis is a medical emergency, and parents or caregivers should call 911 immediately.
Without treatment, classic MSUD can lead to respiratory failure and death.
Intermediate MSUD
Symptoms of intermediate MSUD may present during the first month of life. However, in some cases, intermediate MSUC can remain asymptomatic until later in life. Most children receive a diagnosis between 5 months to 7 years old.
People with intermediate MSUD will have similar symptoms to those with the classic form of the condition, including:
- lethargy
- poor feeding
- poor growth
- ataxia, which refers to a group of conditions that affect a person’s balance, coordination, and speech
- maple syrup odor to earwax, sweat, and urine
The symptoms will be less severe than those in the classic form. However, during a metabolic crisis, the symptoms and risks are the same.
Intermittent MSUD
Intermittent MSUD symptoms might not appear until a child reaches 1–2 years old.
Those with intermittent MSUD experience typical growth and intellectual development. They may also be able to tolerate normal levels of protein.
However, symptoms can appear when a person is ill, fasting, or has consumed large amounts of protein. Symptoms are the same or similar to classic MSUD.
Thiamine-responsive MSUC
Symptoms of this form of MSUD are similar to those with intermediate MSUD.
The condition occurs due to changes to 1 of 3 genes:
- BCKDHA
- BCKDHB
- DBT
Changes to these genes affect human branched-chain alpha-ketoacid dehydrogenase complex (BCKAD) enzymes.
When these enzymes are not present or not working to capacity, the body cannot break down the following branched-chain amino acids (BCAAs):
- isoleucine
- leucine
- valine
These BCAAs are present in all protein foods.
This causes a buildup of amino acids and ketones, which can lead to severe symptoms and complications.
Inheritance
MSUD results from genetic changes passed down from parents to their children. The chromosomes responsible can affect both genders.
For a person to develop the disorder, both biological parents need to be carriers. When two carriers have a child together, they have:
- a 25% chance of having a child with MSUD
- a 50% chance of having a child who is a carrier of MSUD
- a 25% chance of having a child who does not have any copies of the mutated chromosomes
According to the National Organization for Rare Disorders, 1 out of every 185,000 babies is born with the condition.
However, some populations, such as Mennonite and Ashkenazi Jewish populations, have a higher chance of having the genetic mutation.
It is autosomal, which means the mutation occurs on non-X and non-Y chromosomes. This means that a person’s sex does not affect their risk of inheriting the condition.
Can adults get MSUD?
MSUD typically appears within the first 4 weeks of life to 11 years old. Intermittent MSUD symptoms can appear once a child reaches 1–2 years old.
Affected individuals can live to adulthood with proper treatment and dietary changes.
Treatment for MSUD has three parts:
- maintaining a low protein diet
- maintaining levels of BCAAs in the body
- medical intervention during a metabolic crisis
Diet is the primary treatment and management option for MSUD. A person’s diet needs to be very strict and limit proteins.
Some foods a person should avoid include:
- nuts
- meat
- wholegrain flour
- fish
- dairy foods
- eggs
- beans
A person will need regular blood monitoring to make sure the diet is working as expected.
Infants may use a special formula that does not contain the proteins that can cause an issue.
Those with thiamine-responsive MSUD will require thiamine therapy alongside a low protein diet.
Liver transplant
Liver transplants are an experimental form of therapy. People can resume a typical diet following a transplant because the liver can handle processing proteins.
The United Kingdom’s National Health Service (NHS) notes that getting a new liver means that a person will no longer be at risk of having a metabolic crisis.
However, the cost and donor availability may mean that this option is not always available.
Even when following a strict diet, people with MSUD have a risk of experiencing a metabolic crisis. Though there is no standard of treatment when a crisis occurs, doctors will typically treat it aggressively.
Some treatments doctors have tried include:
- dialysis
- insulin
- an insulin and glucose drip
- addition of other amino acids to aid anabolism, which is the process of building new muscle or protein
In addition, they may also treat a person’s specific symptoms. These can vary based on need.
MSUD is a lifelong condition. With treatment and dietary changes, a person can live a typical lifespan into adulthood.
Children and adults need to recognize the signs of a crisis so they can get emergency treatment immediately. This can help prevent complications due to the condition.
Periodic episodes of crisis can cause other complications. This can include the development of learning disabilities and intellectual disabilities.
Doctors diagnose many cases of MSUD via newborn screening programs. After birth, the doctor will take a single blood sample to detect the presence of several different conditions, including MSUD.
If symptoms appear later, Doctors can diagnose it during a routine urine analysis. They may also note the presence of a maple syrup-like smell.
Genetic testing may be available for those in families at risk for MSUD.
Without treatment, some infants are at risk of brain damage, respiratory failure, life threatening coma, and developmental delay.
Delayed development refers to when a child does not gain the developmental skills that are expected of them compared to others of the same age. This can include speech, language, social skills, and cognitive function.
MSUD is a rare disorder caused by a genetic mutation. It requires both biological parents to have and pass on the change to the child.
The condition causes the inability to process certain amino acids and can lead to life threatening complications if not treated.
Treatment typically involves avoiding protein in the diet. When a period of crisis occurs, a person will need immediate medical treatment.
With a strict diet and addressing a metabolic crisis immediately, people can live a full life into adulthood.