Answers to questions families often have about caring for their child with maple syrup urine disease

MSUD is a genetic metabolic condition caused by a build-up of the branched-chain amino acids (BCAAs) leucine, isoleucine, valine and related substances.

A build-up of these amino acids (especially leucine) disturbs brain cells and results in brain swelling and problems with brain cell growth, leading to physical and intellectual disability and, if untreated, death.

The classic form of MSUD usually presents with irritability, extreme sleepiness, and lack of feeding within the first few days of life. A severe episode is called a “metabolic crisis.” In addition to the classic form, there are other forms of the disease – intermediate, intermittent, and thiamine-responsive–which may have a milder and later onset of symptoms, presenting with poor appetite, poor growth, irritability, seizures, or developmental delay in late infancy or childhood. Symptoms and metabolic crisis episodes may happen following an illness or too much protein intake. Seek urgent medical care if you notice these symptoms (irritability, excessive sleepiness, poor feeding, seizures, vomiting, and abnormal breathing).

Urine and blood are tested to make a diagnosis. MSUD is usually diagnosed by newborn screening.

With treatment before crisis occurs, sticking to the special diet for the lifetime, and prompt treatment of illnesses, the outlook is good, and normal development and IQ are expected. Females with MSUD can have healthy children but must strictly follow the special diet and be monitored carefully, particularly after delivery, by metabolic geneticists. Without treatment, intellectual disability, neurologic disturbances, and early death can be expected.

MSUD is an autosomal recessive genetic disorder, meaning both parents must carry a copy of the gene to pass it on to a baby. It also means that siblings of a child with MSUD would have about a 1 in 4 (25%) chance of having the condition. Mutations in 3 genes cause MSUD—BCKDHA, MCKDHB, and DBT. A genetic test can test for these genes when needed.

Infants and children require a specific protein-restricted diet for MSUD (see below) and follow this diet throughout their life. This special diet includes formula and foods low in branched-chain amino acids and, in most cases, supplements of the amino acids isoleucine and valine. Some patients respond to high doses of thiamine with increased protein tolerance. Infants and children with MSUD require close monitoring by their primary care clinician, metabolic geneticist, and nutritionist. Medical treatment is similar in the different types of MSUD, with milder forms requiring less protein restriction. Treatment needs to be continued for life for classic MSUD and all variant forms.

If your child sticks strictly to the special diet, your child should do well. They will, however, need metabolic lab monitoring and possibly special supplements like thiamine. This will make things more difficult for your family and your child. Your metabolic geneticists will help you learn how to follow a diet necessary for the best outcome. A support group may be helpful (see below).

MSUD is an autosomal recessive condition. That means a child needs to get 2 MSUD genes to be affected, 1 from the mother and 1 from the father. When each parent only has 1 MSUD gene, they are unaffected and simply carriers of the gene. It is possible that other extended family members also carry an MSUD gene but have not had a child with another person also carrying the MSUD gene.

The substance causing the odor in urine (and ear wax) in people with MSUD is also found in maple syrup and fenugreek, giving it the same smell.

As soon as a baby is diagnosed, all breastfeeding is stopped, and a special diet is started to keep the baby from getting very sick while blood testing is performed. Unfortunately, even when the mother changes her diet, this doesn’t usually get rid of the amino acids that are bad for the baby. However, breastfeeding can sometimes be restarted in certain situations with very close medical supervision.

Most women with MSUD are able to become pregnant and have healthy babies assuming they are strictly adherent to the diet and are monitored carefully through pregnancy and after delivery. After delivery is actually more of a risky time for the mother with MSUD than pregnancy because of all the changes going on in the woman's body. Metabolic monitoring will need to continue for several months after giving birth. Maple Syrup Urine Disease (GeneReviews)