(MSUD) is an autosomal recessive disorder that has a worldwide incidence of approximately 1:185,000. This disease results from the defective activity of branched chain ketoacid dehydrogenase (BCKAD). This enzyme is responsible for the breakdown of branched chain amino acids (Minnesota Department of Health, 2012). If the activity of this enzyme is defective, branch chain amino acid (BCAA) levels will become elevated in the blood and urine (Dolins, 2016). High levels of leucine, one of the three BCAAs, create a strong affinity for transporting protein to the brain. This large influx of leucine prevents the passage of other amino acids. It is important to recognize that it is leucine that is problematic. However, if valine and isoleucine are too low, leucine will not decrease (Dolins, 2016). With that being said, isoleucine and valine supplementation is only necessary to maintain proper concentrations of plasma leucine, isoleucine, and valine. It is important for leucine and isoleucine to be approximately of equal amounts and for valine to have at least a twofold plasma leucine concentration (Strauss, 2013).
Suggestions related to nutritional therapy include, a diet restrictive of BCAAs, necessary vitamins to prevent malnutrition, and the administration of 150 calories/kg/day as carbohydrates and fat. It is important for individuals to achieve and maintain plasma BCAA concentrations within targeted treatment ranges and monitor nutritional status to promote normal growth, development and health maintenance. The dietary requirements for BCAAs vary as a function of age, growth rate, calorie intake, illness, and residual in vivo BCKAD enzyme activity. The recommendations for maintaining appropriate BCAA blood concentrations are as follows:
Infants can consume formulas that include protein equivalents, such as Ketonex I, BCAD I, and Analog MSUD. Artificial formulas are also available for children and adults with MSUD and consist of synthetic amino acid mixtures that restrict BCAAs, but contain other essential macro- and micronutrients (Boyer, 2015). These formulas are the primary source of calories and nutrients for individuals with MSUD.
It is also important to be aware that low protein foods may lack other important nutrients (Dolins, 2016). In order to prevent malnutrition, it may be necessary to use dietary supplementation to maintain sufficient levels of calcium, magnesium, zinc, folate, selenium, and omega-3 essential fatty acids (Strauss, 2013). Furthermore, thiamine supplementation has shown to be beneficial in those who have residual BCKAD activity (Abdulahad, n.d.). If an individual is responsive to thiamine, supplementation of 50-100 mg/day thiamine is suggested (Strauss, 2013). New and novel therapies, such as the use of phenylbutyrate, are being examined for the treatment of MSUD. However, the research is limited and recommendations for these new therapies cannot currently be addressed.
Abdulahad, B. (n.d.). Thiamin-Responsive Maple Syrup Urine Disease. Retrieved December 13, 2016, from http://www.msud-support.org/index.php/articles/news/592-thiamin-responsive-maple-syrup-urine-disease
Boyer, S. W., Barclay, L. J., & Burrage, L. C. (2015). Inherited Metabolic Disorders: Aspects of Chronic Nutrition Management. Nutrition in Clinical Practice. 30(4). doi:10.1177/0884 533615586201
Dolins, K. R. Inborn Errors of Metabolism [PowerPoint]. Retrieved from https://moodle2.tc. columbia.edu/course/view.php?id=24428
Frazier, D. M., Allgeier, C., Homer, C., Marriage, B. J., Ogata, B., Rohr, F., Splett, P. L., Stembridge, A., Singh, R. H. (2014). Nutrition management guideline for maple syrup urine disease: An evidence- and consensus- based approach. Molecular Genetics and Metabolism. 112(3). https://doi.org/10.1016/j.ymgme.2014.05.006
Strauss, K. A., Puffenberger, E. G., Morton, D. H. (2013). Maple Syrup Urine Disease. GeneReviews. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK1319/
Written by Nicole Lindel, MS in Nutrition Education from Columbia University