Maple Syrup Urine Disease

Marie Lefrançois thought about quitting nutrition twice before finding her niche: treating patients with inborn errors of metabolism (IEM). Over the years, her field has grown tremendously and she now treats over 100 pediatric and adult patients a year. The term ‘inborn error of metabolism’ refers to a series of rare genetic diseases where a child’s enzyme activity is malfunctioning and therefore leads to the accumulation of toxic products in their blood, like urea or ammonia. The buildup of these products occurs when certain foods are digested and can lead to serious health problems and developmental issues. And the main treatment is a specialized diet.

The missing enzyme

In the early 1970s, Quebec started screening for a few types of these diseases at birth, including the most common one, phenylketonuria (PKU). “We can now identify four of these diseases from a heel prick soon after birth, but we’re working on increasing that number,” says Marie. The common thread between all these diseases is that in every case there is a missing or dysfunctional enzyme. For PKU patients, this missing enzyme can lead to the harmful buildup of phenylalanine in the blood, which left untreated, can lead to irreversible brain damage. “Without proper treatment, adults can be left with the mental capacity of a six-month-old,” she says. 

If one of these diseases is detected at birth, the child is immediately put on a specialized diet. Working with these patients, Marie has to either eliminate a type of food completely or reduce it in order to avoid the accumulation of toxic waste in the body. “Certain foods lead to the production of certain toxic products, which is why we need to treat these patients quickly,” she says. “I see newborn patients weekly for the first six months and continue to meet with them regularly into adulthood.” Depending on the condition, Marie will either prescribe a tailor-made formula or will give instructions to the mother on how much breastmilk the baby can drink.

Glycogen storage disease type 1 is another type of inborn error of metabolism and is caused by the buildup of glycogen, a storage form of glucose in the body's liver and muscle cells. In order to reduce glycogen in the body, the patient has to eliminate dairy products (galactose), fruits (fructose), table sugar (sucrose) and sorbitol from their diet. “They also need to wake up in the middle of the night to eat corn starch; otherwise their blood sugar will dip dangerously low and it could even be fatal,” explains Marie. “So cornstarch, a simple cooking ingredient, becomes a medication.”

A balancing act

Prescribing the perfect balance of nutrients is also challenging, because every patient is completely unique. “Not only do I have to make sure the patient reduces the amount of toxic waste in their system, but I also have to make sure that they continue to grow and develop properly,” she says. If the condition is diagnosed early on and the diet is strictly followed, patients can go on to live normal lives, but the buildup of waste can happen quickly if the diet is not respected or when the patient gets sick from a simple cold or gastroenteritis. In some cases, the buildup is so dangerous that a child needs to undergo dialysis in order to remove the toxic products rapidly from their body before starting the diet.

Every time Marie sees a patient, she runs a series of blood tests to analyze the child’s nutritional status and then compares the results to the previous visit to make sure there are no spikes or drops in the patient’s amino acid levels. “If I notice a huge variation it either means that I haven’t prescribed enough of something and I need to adjust their diet, or the child is not following the diet,” says Marie. “In a lot of cases, you can’t visually tell if a child is not following my recommendations. All the answers are in the blood and the diet needs to be followed for life.”

Once a child moves onto solid foods, Marie prescribes specialized food products, like low-protein pasta. These products are not easily accessible and need to be ordered through Le programme alimentaire Québécois pour le traitement de maladies métaboliques héréditaires, which is run out of the Montreal Children’s Hospital. “We run the program for the entire province,” she says. In total, there are five centres in Quebec who treat these types of patients, but only 10 to 12 nutritionists with this specialized training, and Marie is the only one at the McGill University Health Centre.

The right place

One of these patients is seven-month-old Florence Corleto, affectionately nicknamed “Florencita” by the Genetics department. Her mother, also named Florence, was traveling back and forth between El Salvador and Montreal for training in the retail industry, when she was stopped at the airport because airline staff believed she was too pregnant to fly home at 34 weeks. “I felt fine, but they wanted me to get a doctor’s note to clear me for travel,” she says. After meeting with a doctor, they confirmed that her daughter was breeched and she needed to have a c-section. “My plan was to deliver and go back home immediately, but it didn’t work out that way,” recalls Florence.

At six days old, Florencita was barely eating and she was sleeping 21 hours a day. Florence brought her to the Emergency department at the Children’s where numerous tests were done, including a lumbar puncture to rule out meningitis. “At first they thought she was dehydrated because she was sleeping so much, but she didn’t become active even after they rehydrated her,” she says. The team also noticed extremely high leucine levels in her body.

The Genetics department was called in and they diagnosed Florencita with maple syrup urine disease. The disease is categorized by the toxic buildup of an amino acid, known as leucine, in the bloodstream. “In those cases this buildup of leucine ends up causing the urine to smell like maple syrup, hence the name,” explains Marie. If the disease is caught late, children are left with many serious health issues, including severe brain damage; in some cases, it can cause death.

Florencita was immediately put on hemodialysis to flush the leucine from her body and she was admitted to the Pediatric Intensive Care Unit. “Her levels were so high they were worried she was going to go into a coma or die,” says her mother. Doctors and nurses surveyed her closely and monitored her kidneys, amino acid levels and development daily. Marie also prescribed her a special formula, plus additional supplements to cover all her nutritional needs. As she grows, Florencita will continue to be limited in terms of what she can eat. She won’t be able to consume high-quality protein foods or dairy products, because her body can’t process or digest protein. “She will have to become a strict vegan, but we’ll still have to keep track of all the leucine she consumes, which is common in foods like beans and corn,” says Florence.

On top of dealing with her daughter’s illness, Florence is also dealing with another horrible ordeal: she can’t go home. “There are no specialists in El Salvador who deal with this disease. There are also no labs that can run her bloodwork and her special formula is not available in my country,” she says. “I am completely alone here in Canada, but if we go back home right now, my daughter could die.” Marie is now looking into other healthcare options closer to their home, in either Costa Rica or Mexico City.

“Every day I think about how blessed we are,” says Florence. “My daughter wouldn’t be alive today without everything the hospital team and this province has done for us. How ironic that my daughter was diagnosed with this disease in the capital of maple syrup?”


Photo credit: Owen Egan