Maple Syrup Urine Disease
Note: This is a highly specialized area of practice. Errors in judgment or errors from
inexperience in this area can lead to intellectual disability and other serious complications.
Please refer patients to an experienced colleague if necessary.
Maple syrup urine disease (MSUD) is an inherited disorder of isoleucine, leucine, and valine
(branched-chain amino acids [BCAAs]) metabolism, caused by decreased activity of the
branched-chain alpha-keto acid dehydrogenase complex (BCKAD), which normally helps to
break down the BCAA. The amino acids and their by-products build up in the body, and this
accumulation of toxic substances leads to serious health problems.
MSUD occurs in 1 of 180,000 to 225,000 live births, with a much higher prevalence among the
Mennonite and Ashkenazi Jewish populations. A milder form of MSUD is partial enzyme
deficiency, which only is manifested sometimes. Intermediate MSUD usually is diagnosed
between 5 months and 7 years of age.
Symptoms and possible outcomes of MSUD
Infants appear well at birth and are fine until they consume protein. Some infants die within 10
days of birth, following seizures and apnea. Neurological dysfunction is progressive. Urine and
earwax are likely to smell of maple syrup, from elevated levels of amino acids in the urine.
The infant may suffer from:
 Poor sucking
 Respiratory problems
 Lethargy
 Vomiting
 Shrill crying
 Excessive rigidity and flaccidity
 Severe hyperextension and spasticity (similar to that seen in cerebral palsy or tetanus)
 Seizures
In adulthood, leucine intoxication often presents with hallucinations, anorexia, mood swings,
cognitive impairment, and ataxia. Acute pancreatitis sometimes develops as leucine
concentration returns to normal. Encephalopathy and brain herniation may result during medical
crisis. Immune suppression is not uncommon. The brain is sometimes severely and permanently
damaged during times of physical stress, such as illness.
Children may suffer from attention disorders, impulsivity, or hyperactivity, while adults often
develop mental illness.
Nutrition therapy for MSUD
 Restriction of BCAAs is required
 The diet generally revolves around the intake of specialized BCAA-free medical formula and
small, carefully controlled amounts of BCAA-containing foods
 Infants often are given BCAA-free formula, breast milk, or regular infant formula; a solution
of isoleucine, valine and leucine; and glutamine and alanine supplementation
 Energy needs—120 to 150 kilocalories (kcal)/kilogram (kg)/day for infants, 80 to 100
kcal/kg/day for children, and 40 to 50 kcal/kg/day for adults; energy needs sometimes are 40%
higher when patient is in metabolic acidosis
 Infants and children require 2.5 to 3 grams protein/kg/day
 Medical foods often do not contain selenium or B vitamins (supplementation required)
 Zinc and omega-3 fatty acid deficiencies are common
 Insulin often is necessary during episodes of metabolic decompensation
 When feeling well, those with intermediate MSUD usually can tolerate normal intake of
leucine
 Thiamine therapy has aided some cases of MSUD, but the thiamine always is combined with
BCAA restriction, making it difficult to tell the true efficacy of thiamine treatment
 High-protein foods (meat, poultry, eggs, etc) are omitted from the diet
Medical treatment of MSUD
 Peritoneal dialysis or hemodialysis is used to reduce the levels of the amino acids
 Liver transplant appears curative
 Gene therapy research looks promising, but further research is needed
References and recommended readings
Bodamer OA. Maple syrup urine disease. Medscape Web site.
http://www.emedicine.com/ped/topic1368.htm. Accessed April 16, 2013.
PubMed Health. Maple syrup urine disease. National Center for Biotechnology Information, US
National Library of Medicine, National Institutes of Health Web site.
http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001411/. Accessed April 16, 2013.
Trahms CM, Ogata BN. Medical nutrition therapy for genetic metabolic disorders. In: Mahan
LK, Escott-Stump S, Raymond JL. Krause’s Food and the Nutrition Care Process. 13th ed. St
Louis, MO: Elsevier Saunders; 2012.
Welcome to the MSUD Family Support Group. Maple Sugar Urine Disease Family Support
Group Web site. Available at: http://www.msud-support.org. Accessed April 16, 2013.
Review Date 4/13
K-0587