Medical Nutrition Therapy Diet: Maple Syrup Urine Disease (MSUD)
1. Purpose
a. Nutrition Indicators
i. Symptoms usually being between ages 4 and 7 days or when infant
is first fed protein
ii. Symptoms include:
1. Lethargy, poor suck, decreased intake, weight loss
2. Neurologic signs: alternative increase and decreased motor
tone; abnormal movements (dystonia)
3. Ketosis, abnormal maple syrup odor, seizures, coma,
cerebral edema, and death
iii. Nutrition screening done at birth in infants with a family history of
MSUD
1. Some infants are symptomatic before testing results are
even known
iv. Various degrees of disabilities depending on when treatment was
started and how strict and controlled the diet was
v. Four types of MSUD
1. Classic: less than 2% of normal activity of BCKD; more
common and most severe
a. Symptoms present within a week of birth
2. Intermediate: 3-30% of normal activity of BCKD; less
severe than classic and less common
a. Symptoms appear better 5 months and 7 years of
age and include delayed development, maple syrup
odor in urine, and seizures
3. Intermittent: 5-20% of normal activity of BCKD; less
severe than classic and less common
a. Episodes of acute loss of metabolic control usually
begin between 5 months and 2 years of age
b. During episodes: difficulty walking and keeping
balance, lethargy, behavior/personality changes, and
maple syrup odor in urine
4. Thiamine-responsive: 30-40% of normal activity of BCKD;
similar to intermediate and intermittent although less
common
a. Responsive to thiamine in daily doses of 100150mg
b. Mennonite classic is not a thiamine-responsive type
b. Criteria to Assign the Diet
i. High levels of plasma amino acids leucine (>170 micro mol/L),
isoleucine (>140 micro mol/L) and valine (>350 micro mol/L)
c. Rationale for Diet
i. Individuals cannot break down the amino acids leucine, isoleucine
and valine and these buildup in the blood
2. Population
a. Overview
i. MSUD is a metabolism disorder caused by a gene defect that is
passed down through families in which the body cannot break
down certain proteins
ii. Inheritance: autosomal recessive
iii. Individuals cannot break down the amino acids leucine, isoleucine,
and valine
iv. Affects 1 in 185,00 babies born worldwide
v. 1 in 380 babies from the Old Order Mennonite population are
affects by MSUD
vi. 1 in 81 in Ashkenazi Jews
vii. More common in people of French-Canadian ancestry and
Ashkenazi Jewish ancestry
b. Disease Process
i. MSUD is inherited in an autosomal recessive manner and each
parent has to have the recessive gene for it to be passed down to
the child
ii. At conception, if both parents have the gene, there is a 25% chance
of being affected, a 50% chance of being an asymptomatic carrier
and a 25% chance of being unaffected and not a carrier
iii. MSUD is a rare disorder of catabolism of the branched chain
amino acids (BCAAs) causing elevated levels of leucine,
isoleucine, and valine and their respective branched chain
ketoacids (BCKA) to accumulate in the body
1. Caused by the absence branched-chain ketoacid
dehydrogenase (BCKAD), which breaks down leucine,
isoleucine, and valine
a. These cannot be broken down and build-up
iv. Infants appear normal at birth, but only remain well for a few days
1. Symptoms are usually associated with the ingestion of
dietary protein and soon progress from poor feeding and
vomiting to lethargy and coma
2. A high-pitched cry, irritability, convulsions, spasticity, and
CNS depression are additional signs, with severe metabolic
acidosis and hypoglycemia
3. Plasma leucine begins to rise, usually within 24 hours of
birth and within a few days, ketoacids appear in the urine,
which give the urine the characteristic sweet maple syrup
odor from which the disease gets its name
v. Even in the mildest form, MSUD can result in mental retardation
vi. There are less severe variants of the disease and some mild forms
may go undetected for some time until an illness reveals the
biochemical abnormalities present
vii. Brain damage can occur in left untreated, which can lead to mental
retardation or spasticity
viii. Treatment includes dietary leucine restriction, high-calorie BCAAfree formulas, supplementation with isoleucine and valine and
frequent clinical and biochemical monitoring
ix. Lifelong disease with dietary treatment as the key to leading a
healthy life
x. Times of high stress including infection, fever and poor nutrition
can lead to complications if not treated immediately and mental
retardation or death, in more severe cases, may occur
xi. Strict dietary treatment can allow children to grow and live a
healthy adulthood
c. Biochemical and Nutrient Needs
i. A special diet free of branched-chain amino acids is started when
amino acid levels are normal
ii. Lifelong treatment includes a man-made infant formula made with
low levels of the amino acids leucine, isoleucine and valine
iii. Upon diagnosis and during episodes of the disease, treatment
involves eating a protein-free diet
iv. Peritoneal dialysis or hemodialysis can be used to reduce the levels
of amino acids as well
v. Important to follow diet to prevent neurological damage
vi. Some individuals with MSUD are thiamine-responsive and have
30 to 40% the normal activity of the BCKAD enzyme and can
tolerate some protein in their diet
vii. Thiamine is given to newly diagnosed infants to determine if they
are responsive to it and if it can help with their treatment and diet
3. General Guidelines
a. Nutrition Rx
i. Initial treatment involves a complete protein-free diet, initiate
TPN, provide high calories, lipids and in some cases insulin
ii. Add leucine to diet when levels are normalized
iii. Long-term restriction of BCAA intake in order to control plasma
BCAA levels
iv. Plasma leucine levels should not exceed 200 mmol/L in children
v. BCAA requirement in patients is mainly determined using indirect
markers such as growth and elimination of symptoms
vi. Thiamine-responsive MSUD is due to a reduced affinity of the
mutant branched-chain alpha-keto acid dehydrogenase for thiamin
pyrophosphate
1. 100-150 mg of thiamin should be give to individuals for up
to 3 months to determine responsiveness
vii. Protein is restricted but carbohydrates and fat should be consumed
as part of a healthy diet according to age or individual
viii. When solid food is introduced around six months of age, babies
need to eat mainly fruits and vegetables and specific baby foods
ix. Later, they can eat a wider range of lower protein foods, including
special bread and pasta
x. Supply isoleucine and valine to meet growth needs and avoid
deficiencies and protect against high leucine levels
xi. Add glutamine and alanine to prevent low levels of these two
amino acids
xii. Avoid prolonged low levels of BCAAs because this can lead to
poor growth, decreased appetite, rashes, and skin infections
xiii. Vitamin and mineral supplementation may be necessary
xiv. Do not restrict activity in child and adulthood
b. Adequacy of Nutrition Rx
i. Diet low in BCAAs, but protein can be provided based on the
amount of leucine allowed
ii. Special commercial formulas specifically low in BCAAs can help
individual get the protein they need
iii. Consumption of carbohydrates and fats should be adequate and in
times of metabolic stress or illness, should be consumed in greater
amounts
c. Goals
i. Normal weight gain, linear growth and head growth
ii. Normal psychomotor development, as assessed by valid
developmental screening tools
iii. Age-appropriate tolerance of leucine, isoleucine, and valine with
stable plasma BCAA concentrations of BCAA concentration ratios
iv. Avoidance of essential amino acid, fatty acid, and micronutrient
deficiencies
v. Monitor BCAA levels closely, especially leucine to avoid
neurological complications
vi. Self-monitoring in child and adulthood and careful attention by
parent during infancy
d. Does it Meet DRI
i. Carbohydrates and fats will meet DRI values, but protein may be
on the low end due to restrictions
ii. Special formulas, protein alternatives, and special low-protein
foods, and high-calorie supplements can be used to provide
necessary vitamins, minerals and amino acids, except for leucine,
isoleucine and valine
4. Education Material
a. Nutrition Therapy
i. Provide education to the patient and family about how to calculate
leucine and amount of protein allowed from foods per day
ii. Provide a list of foods allowed and those to avoid
iii. Help patient and family come up with a “sick day” meal plan to
help avoid trips to the ER
iv. Provide instructions on when to contact your doctor when episodes
occur
v. Provide basic education principles of dietary treatment
b. Ideas for Compliance
i. Refer the family to a specialist on the disease or support groups
ii. Follow up with the patient and family as needed or every 6 to 12
months
iii. Provide family with resources to help educate young children on
what they can and cannot eat
5. Sample Menu
a. Foods Recommended
i. Low-protein diet must be followed
ii. Special medical formula is used as a substitute for milk and gives
the child the nutrients and protein they need while keeping their
BCAA levels in a safe range
iii. Foods containing carbohydrates and fats can be consumed as usual
and not restricted
iv. Foods naturally low in protein or those that contain essentially no
protein such as some fruits and vegetables in small portions
v. Special breads and pasta
vi. Replaced dairy milk with rice milk (check the label)
b. Foods to Avoid
i. Cow’s milk and regular formula
ii. Meat, fish, cheese and eggs
iii. Regular flour, dried beans, nuts and peanut butter
c. Example of a Meal Plan
i. Breakfast: 8 oz formula, ½ cup Kellogg’s Fruit Loops, 4oz apple
juice, 1 small banana
ii. Lunch: 8oz formula, 1 slice Loprofin bread, 2 slices of tomato, 2
slices lettuce, 2 slices onion, 1 Tbsp. ranch dressing, 1 cup grapes,
2 large rice cakes
iii. Snack: 6oz formula, 1 medium orange
iv. Dinner: 8oz formula, medium salad with assorted vegetables, 2
Tbsp. salad dressing, 1 cup Aproten spaghetti with 2 Tbsp. butter
v. Snack: 6oz formula, 1 cup popcorn (check brands for lowest
protein content)
6. Websites
a. Organizations with Websites
i. MSUD Family Support Group (www.msud-support.org
ii. National Organization for Rare Disorders (www.rarediseases.org)
iii. CLIMB (Children Living with Inherited Metabolic Diseases) UK
based organization (www.climb.org.uk/)
iv. Chicago Center for Jewish Genetic Disorders
(www.jewishgenetics.org)
v. Genetic Disease Foundation (www.geneticdiseasefoundation.org)
vi. National Newborn Screening and Genetics Resource Center
(http://genes-r-us.uthscsa.edu/)
b. Government Websites
i. National Institutes of Health (www.nih.gov/)
ii. U.S. National Library of Medicine (www.nlm.nih.gov/)
7. References
a. Journal Article References
i. Academy of Nutrition and Dietetics. (2010). Providing nutrition
services for people with developmental disabilities and special
health care needs. Journal of the Academy of Nutrition and
Dietetics, 110(2), 206-307.
ii. Chuang, D. T. (1998). Maple syrup urine disease: It has come a
long way. Journal of Pediatrics, 66(6), 1042-1048.
iii. Edelmann, L., Wasserstein, M. P., Kornreich, R., Sansaricq, C.,
Snyderman, S. E., & Diaz, G. A. (2001). Maple syrup urine
disease: Identification and carrier frequency determination of a
novel founder mutation in the Ashkenazi Jewish population.
American Society of Human Genetics, 69(4), 863-868.
iv. Marsden, D., Larson, C., & Levy, H. L. (2006). Newborn
screening for metabolic disorders. Journal of Pediatrics, 148(5),
577-585.
v. Strauss, K. A., Wardley, B., Robinson, D., Hendrickson, C., Rider,
N. L., Puffenberger, E. G., Shlemer, D., Moser, A. B., & Morton,
D. H. (2009). Classical maple syrup urine disease and brain
development: Principles of management and formula design.
Molecular Genetics and Metabolism, 99, 333-345.
b. Other References
i. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001411/
ii. http://www.umm.edu/ency/article/000373all.htm
iii. http://www.state.nj.us/health/fhs/nbs/documents/maple_prof.pdf
iv. http://www.ncbi.nlm.nih.gov/books/NBK1319/
v. http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease
vi. http://chfs.ky.gov/NR/rdonlyres/A9B53EE8-3FE7-4DE8-8C09E66BC8C681C8/0/MapleSyrupUrineDisease.pdf
vii. http://health.nytimes.com/health/guides/disease/maple-syrup-urinedisease/overview.html
viii. http://children.webmd.com/maple-syrup-urine-disease-11168
ix. https://www.counsyl.com/diseases/maple-syrup-urine-diseasetype-1b/
x. http://www.msudsupport.org/index.php?option=com_content&view=article&id=219
%3Adescription-a-treatment-of-maple-syrup-urinedisease&Itemid=120
xi. http://www.idph.state.il.us/HealthWellness/fs/msud.htm
xii. http://emedicine.medscape.com/article/946234-treatment#showall
xiii. http://www.hgsa.org.au/website/wpcontent/uploads/2010/02/MSUD2.pdf