Get to Know Maple Syrup Urine Disease, a Genetic Disease That Causes Sweet-Smelling Urine

In the first few weeks of life, babies are sometimes offered a newborn blood spot screening to check for an inherited condition such as maple syrup urine disease (MSUD). This is a very rare genetic (hereditary) disease. However, it is a very serious condition. If not treated properly, it can lead to coma or death .

Definition 

Maple syrup urine disease (MSUD) is a rare metabolic disorder that some babies are born with. It is caused by a defect in an enzyme that breaks down certain amino acids.

This means the body can’t process certain amino acids (the “building blocks” of proteins), causing a buildup of harmful substances in the blood and urine. Normally, our bodies break down protein foods like meat and fish into amino acids. Any amino acids that aren’t needed are usually broken down and excreted from the body. Babies with MSUD can’t break down amino acids called leucine, isoleucine, and valine. Very high levels of these amino acids are dangerous.

There are four main types of maple syrup urine disease :

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 usually 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 causes symptoms to appear. People with intermittent MSUD can usually tolerate higher levels of three amino acids than people with classic MSUD.

Responsive to thiamine

This type of MSUD responds to treatment with high doses of vitamin B1 (thiamine) along with a restricted diet. With treatment, people with thiamine-responsive MSUD have a higher tolerance to the three amino acids.

Symptom

As the name suggests, newborns with MSUD have urine or earwax that smells sweet, like maple syrup. Maple syrup urine disease is often classified by the pattern of signs and symptoms. The most common and severe form of the disease is the classic type, which appears soon after birth or within 48 hours of birth. Variant forms of the disorder become apparent later in infancy or childhood and are usually milder, but they still cause developmental delays and other health problems if left untreated.

Infants or children with MSUD may also experience symptoms, such as:

• have problems with eating
• vomit
• become cranky or irritable
• cry in a high pitch
• have low energy levels and be very sleepy
• difficulty growing and gaining weight
• Unusual muscle movements and muscle tension that cause the head, neck, and spine to curve backwards.
• developmental delay
• convulsions.

Reason

Amino acids help children grow and develop. The body uses them to make proteins. In MSUD, three amino acids (leucine, isoleucine, and valine) are not broken down. These amino acids and their byproducts then build up in the blood, damaging the brain and other organs.

MSUD occurs when there is a change (mutation) in the gene that makes the enzyme that breaks down these three amino acids, which are found in food.

Children with the condition likely inherit two altered MSUD genes, one from each parent. Parents who have one altered gene do not have any symptoms, but can pass the gene on to their children. 

The risk for two carrier parents to pass on the non-functioning gene and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier, like the parents, is 50% with each pregnancy. The chance of a child receiving the working gene from both parents is 25%. The risk is the same for boys and girls equally.

Risk Factors

Maple syrup urine disease can affect anyone, but people who have close family ties to their parents are more likely to have the metabolic disease. For this reason, MSUD is more common in certain ethnic groups. 

In the United States, Mennonites often experience this genetic disease, with an estimated incidence of about 1 in 380 newborns. Because, many members of the community often marry each other. In addition, quoted from the National Organization for Rare Disorders , MSUD occurs in the Ashkenazi Jewish population with an estimated incidence of 1:26,000 live births

Frequency of Occurrence

Maple syrup urine disease is very rare. It occurs in about 1 in every 185,000 births worldwide. It occurs more often in populations with small gene pools or when cousins ​​and other close relatives have children together.

Diagnosis

Doctors diagnose classic MSUD with a newborn screening (blood test) soon after the baby is born. People with intermediate, intermittent, or thiamine-responsive MSUD may not show signs of the disease until toddlerhood or early childhood. In these cases, doctors diagnose MSUD with a blood test and by evaluating the child’s symptoms, including detecting a distinctive sugar or maple syrup odor in their sweat and urine. Genetic testing of the white blood cells in the blood can now help confirm the diagnosis and also help identify the type of MSUD.

Handling

Diet

Doctors can manage MSUD by controlling the levels of three amino acids (leucine, isoleucine, and valine) in the patient’s body. Children with MSUD must always follow a strict diet that provides essential nutrients but severely limits the amount of the three amino acids. Thiamine-responsive MSUD can be managed with high doses of vitamin B1 (thiamine) and a strict diet.

The National Health Service explains that children diagnosed with MSUD are first referred to a specialist metabolic dietitian and put on a low-protein diet. They may also need to take medication. The diet is adjusted to reduce the amount of amino acids they receive, especially leucine, valine and isoleucine.

High protein foods need to be limited, including:

• meat
• fish
• cheese
• egg
• nuts.

A dietitian will provide detailed advice and guidance, as babies still need some of these foods for healthy growth and development.

Some children need to take isoleucine and valine supplements in addition to their prescribed diet. This helps maintain healthy levels of the amino acids in the blood without causing harm. Blood tests are needed to monitor these levels.

Breast milk and formula also need to be monitored and measured before feeding the baby, as recommended by nutritionists. Regular infant formula contains amino acids that need to be limited, so special formula is used. It contains all the vitamins, minerals, and other amino acids that the baby needs.

Children with MSUD will need to follow a low-protein diet for the rest of their lives to reduce the risk of metabolic crisis. As children get older, they will eventually need to learn how to control their diet and will continue to work with a dietitian for advice and monitoring.

Intensive care in hospital

Doctors monitor children with MSUD throughout their lives to make sure the three amino acids do not exceed a person’s tolerance level and begin to cause damage. When someone with MSUD is sick, has a fever, is unable to keep food down due to vomiting or diarrhea, or when the amino acids rise to dangerous levels, they should be hospitalized immediately. 

In the hospital, doctors can provide treatment, such as:

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

Liver transplant

There is a permanent cure for children with maple syrup urine disease. According to the Cleveland Clinic , since 2004, liver transplants have been very successful in treating individuals with classic MSUD. With a new liver, the child can produce the enzymes they need to break down three amino acids that are formed in the body. 

After a liver transplant, the child can eat an unrestricted diet, live asymptomatically, and avoid further cognitive problems. Children with MSUD still carry the gene for the disorder and can therefore still pass it on to their offspring. 

Genetic counseling 

Parents may also want to consider genetic and genomic testing. This may lead to a referral for genetic counseling, which offers support, information, and advice about genetic conditions.

Possible Complications

Children with maple syrup urine disease 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 break easily.
• Swelling of the pancreas/pancreatitis, especially during a crisis.
• Chronic headaches caused by increased blood pressure in the skull.
• Movement disorders such as tremors and uncontrolled muscle contractions.
• Coma and death arising from critical conditions such as infection, stress or poor dietary control.

According to Myriad Genetics , if left untreated, life-threatening coma or respiratory failure can occur within 7 to 10 days and death can occur within the first two months. After a lapse of treatment, classic MSUD can cause brain damage.

Prevention

There is no way to prevent maple syrup urine disease. You can lower your risk of having a baby with MSUD by making sure your partner is not related to you. If you have a sibling or other relative with MSUD, you should talk to your doctor before you become pregnant to discuss the possibility of passing the disease to your child. Your doctor may test you  to see if you are a carrier of the gene that causes maple syrup urine disease .

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Republished with permission from theAsianParent Indonesia