MAPLE SYRUP URINE DISEASE (MSUD)
Patient Description
27-year old female looking to get pregnant. MSUD runs in family and after genetic screening,
finds she is a carrier as well. Her husband is also a carrier. She is consulting with medical
professionals, including dietitian, doctor, and genetic counselor to identify risks, complications,
and what to expect if she were to have a child with this genetic disease.
I. Etiology
a. MSUD is a genetic metabolism disorder passed down through families in which
the body cannot break down certain parts of proteins. This disorder is caused by a
gene defect in which the amino acids leucine, isoleucine, and valine cannot be
broken down, resulting in a build up of chemicals within in the blood. MSUD is
inherited in an autosomal recessive pattern. For a child to get the disease, he or
she must inherit a defective copy of the gene from each parent. If both parents
carry the MSUD gene, each of their children has a 25 percent chance of getting
the disorder, and a 50 percent chance of being a carrier.
b. In most populations, MSUD is an extremely rare disorder; only in 1 in 180,000
babies are born with it.
II. Diagnostic Measures
a. In some states, all babies are screened for MSUD within 24 hours after birth. A
blood sample taken from the baby's heel is analyzed for high leucine levels.
Normal leucine levels are less than 4 mg/dL (0.4 mg/ml). Even a slight elevation
of plasma leucine in the normal newborn is unusual unless the baby is premature
and/or receiving IV amino acid preparations.
b. Diagnosis can usually be suspected from the characteristic burnt caramel smell of
the urine and is confirmed by abnormal levels of amino acids and keto acids in the
blood and urine. Other symptoms may include metabolic acidosis and depressed
serum alanine levels. The enzyme defect may also be detected in leukocytes
and/or fibroblasts.
c. The method screening for birth is for deficiency of branched-chain alpha-ketoacid
dehydrogenase activity in cultured chorionic villi.
d. Symptoms begin as soon as an infant is fed protein, usually shortly after birth.
Some of the first symptoms include: poor appetite, weak suck, weight loss, high
pitched cry, urine that smells that like maple syrup or burnt sugar. Babies with
MSUD will also have episodes of illness called metabolic crisis, symptoms of
which are: extreme sleepiness, sluggishness, irritable mood, and vomiting.
III. Treatment
a. Medical surgical, psychological
i. Prompt treatment is needed to prevent mental retardation and serious
medical problems. Children are given a special medical formula as a
substitute for milk. This formula gives them the nutrients and protein they
need while helping keep their BCAA (branch chain amino acid) levels in a
safe range.
ii. Regular blood tests to measure amino acid levels are necessary
iii. Liver transplantation – the first liver transplantation done in 1997 on an
infant with acute liver failure due to a cause outside of MSUD, the infant’s
MSUD was metabolically corrected and cured. Infants undergoing liver
transplants are able to resume normal liver function and follow an
unrestricted diet.
iv. Genetic counseling and genetic counselors who have special training in
inherited disorders are available to families who have children with
MSUD and can answer questions about how the condition is inherited,
choices during future pregnancies, and how to test other family members.
b. Medical Nutrition Therapy
i. Diet is absolutely crucial to healthy development and prevention of further
complications in children with MSUD.
ii. The primary goal is to maintain BCAA’s, particularly leucine, within
normal limits; studies have shown a correlation between cognitive decline
and elevated blood leucine levels. Protein from food is digested and
broken down into these amino acid components and are necessary for
making tissues for the body. BCAA’s are essential and must be consumed
from food. Normally, if more protein is eaten than is needed, it will be
broken down to make energy. However, in MSUD the enzyme required is
either present in inadequate amounts or is not functioning properly. This
causes toxic levels of leucine and its ketoacid to accumulate.
iii. Maintaining blood BCAA levels within recommended limits while
ensuring adequate calories and protein and avoiding nutritional
deficiencies is the primary goal of MNT for MSUD patients. To do so, the
diet must strictly restrict BCAA.
1. The best way to ensure adequate protein intake is by consuming a
metabolic formula with all of the essential amino acids needed by
the body without the BCAA. These will provide up to 90 percent
of the patient’s protein intake. Formulas include: Analog (infant),
Ketonex1 (infant), BCAD1 (infant), Acerflex(teen/adult),
Maxamaid MSUD (teen/adult), and BCAD2 (teen/adult). This
protein is best used by the body when taken multiple times a day.
iv. It is important to keep track of the exact amount of protein and
specifically, leucine, content in foods by using a food list. Use one food
list consistently. Leucine should be added to the diet in the form of regular
formula or table foods when leucine levels are normalized (primarily in
infants). Other amino acids (isoleucine, valine) should be supplemented;
tyrosine also helps decrease leucine brain levels.
v. Despite dietary compliance, illness can cause elevated levels of BCAA.
Pushing fluids and calories during this time helps flush out toxins; parents
are also asked to monitor metabolic control by checking the urine for
ketones.
vi. Because of the restrictive nature of this diet, nutritional deficiency is a
possibility. Deficiencies in trace minerals, like sodium, have been
reported; marginal calcium intake along with chronic acidosis related to
elevated branch chain ketone levels can lead to decreased bone
mineralization (increasing risk for osteoporosis); deficient levels of
essential fatty acids, found primarily in the restricted protein sources, can
occur.
vii. Over-restriction of protein can develop, causing poor growth, fat deposits
in the muscle, decreased REE, skin rashes, decreased immunity and
appetite, and decreased hair loss. Valine deficiency can lead to poor
growth, irritability, drowsiness, and decreased blood protein levels.
Therefore it is essential that MSUD patients are receiving sufficient
amounts of all EFAs.
viii. Diet also depends on the type of MSUD. With classic MSUD, there is less
than 2 percent of normal activity of the enzyme branched-chain a-Keto
acid Dehydrogenase (BCKD) and is the most severe and most common;
leucine is more elevated than other BCAA’s. Intermediate MSUD is less
severe and less common than classic and has about 3 to 30 percent of
normal BCKD activity. All BCAA levels are elevated, but leucine is less.
Intermittent MSUD has about 5 to 20 percent of normal enzyme activity
and is also less common.
1. Thiamine-responsive MSUD responds to thiamine in daily doses of
100 to 150 grams and abnormal BCAA’s are only present with
metabolic episodes. Thirty to 40 percent of enzyme activity is
present.
ix. Long term treatment requires the use of special medical food to provide
protein intake of 2 to 2.5 grams/kg daily. A diet low in leucine, 300 to 600
mg established by age 2 to 3 is maintained daily for the rest of the
individuals life.
x. Dietary treatment changes with age. It is important to have regular follow
up meetings to make sure that treatment is adjusted appropriately to
account for growth and metabolic stability.
1. Around 6 months, babies need to eat mainly fruits and vegetables
and certain baby foods. Later on, they can eat a wider range of low
protein foods, including special bread and pasta.
xi. Physical activity is important; with more muscle, a better tolerance of
leucine in the diet is created.
xii. The effectiveness of treatment is monitored by nutritional status,
metabolic control and compliance. Strict dietary control is needed for life.
c. Prognosis
i. If untreated, MSUD is life threatening.
ii. With prompt and lifelong treatment, children with MSUD often have
healthy lives with typical growth and development. However, even with
treatment, some may still develop swelling of the brain and have episodes
of metabolic crisis that may develop permanent brain damage. This can
cause lifelong learning problems, mental retardation or spasticity.
iii. Even with dietary treatment, stressful situations and illness can still cause
high levels of certain amino acids.
References
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Australasian Society for Inborn Errors of Metabolism (2005). The ASIEM low protein handbook
for MSUD. Nutriticia. Retrieved from
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Internet. Jan. 23, 2013.
“Diagnostics for MSUD.” (n.d.) Clinical Cases in Biochemistry. Retrieved from
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Genetic Science Learning Center (2012). Maple syrup urine disease (MSUD). Learn Genetics.
Retrieved from http://learn.genetics.utah.edu/content/disorders/whataregd/msud/.
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Nelms, Sucher, Lacey, & Roth. (2011). Nutrition therapy and pathophysiology. Belmont, CA:
Madsworth, Cengage Learning.
“Maple Syrup Urine Disease.” (2012). National Institutes of Health: Office of Rare Diseases
Research. Retrieved from
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disease.aspx. Online. Internet. Jan. 23, 2013.
“Maple Syrup Urine Disease: MSUD.” (2011). PubMed Health. Retrieved from
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Mazariegos, George (2013). Maple syrup urine disease. Children’s Hospital of Pittsburgh.
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Wappner, Rebecca (2001). Description and treatment of maple syrup urine disease. MSUD
Family Support Group. Retrieved from http://www.msud
support.org/index.php?option=com_content&view=article&id=219%3Adescription-atreatment-of-maple-syrup-urine-disease&Itemid=120. Online. Internet. Jan. 23, 2013.