1. Maple Syrup Urine Disease
Brittany Taylor
Rebecca Linstead

2. Overview of Disorder
The body is unable to process leucine, isoleucine and valine because at least one of the four genes that code for the enzyme responsible for breaking down these amino acids has a mutation.

4. Four Forms of MSUD Enzyme activity = <2% Classic neonatal form:
Most common; most severe
Absence or significant decrease in function of the enzyme branched-chain ketoacid dehydrogenase, which is needed to break down the branched-chain amino acids
Infants don’t show symptoms until days four to seven of life

5. Intermediate Form Enzyme activity = 3-30%
A higher level of enzyme is present than in the classical form, therefore allowing a higher tolerance of leucine
Management is the same in both intermediate and classical forms of MSUD

6. Intermittent Form Enzyme activity = 5-20% Mild form of MSUD
Greater amount of enzyme activity is present
An affected child will not show symptoms until around months of age
Symptoms are usually brought on by a surge in protein intake or illness

7. Thiamine-Responsive Form
Enzyme activity = 2-40%
Most rare form
A child with this form may take large doses of thiamine to increase their enzyme activity

8. Diagnosis
Suspect of MSUD results from the characteristic odor of maple syrup in the urine
Confirmed diagnosis with abnormal amounts of keto acids and amino acids in blood and urine
Serum alanine levels may also be depressed

9. Genetic Inheritance Autosomal recessive
Each parent carries one normal copy and one mutated copy of the gene but does not show symptoms themselves

10. Signs and Symptoms Poor appetite Irritability Maple smelling urine
Mental retardation
Seizures
Coma and death if left untreated
Infants will…
Lose their sucking reflex
Become limp with episodes of rigidity

11. Incidence In the US = 1 in 185,000 births
The Mennonite population in Lebanon and Lancaster counties of Pennsylvania have an incidence of 1 in 176 newborns
Founder’s effect?

12. Prognosis Overall very poor if left undetected/untreated
With treatment and proper dietary management, the prognosis is good
However, severe stress and illness can cause a surge of certain amino acids

13. Medical Management of MSUD
Long-term management via diet
Restriction of leucine, isoleucine and valine
Treatment of acute metabolic decompensation
Liver transplant may be an option but is associated with other consequences (transplant mediations for life)

14. Goal of Nutritional Management
Ultimate goal is to restrict branched-chain amino acids while avoiding impairment of growth and intellectual development
Maintain normal levels of branched-chain amino acids, particularly leucine

15. General Nutritional Management
Lifelong nutrition support via formulas and foods with minimal (if any) branched-chain amino acids
Leucine intake is carefully monitored and calculated following the measurement of plasma branched- chain amino acids

16. Nutritional Management during Acute Illness
Situational stress and illness may result in metabolic decompensation
Initiate IV glucose to promote anabolism
Stop intake of branched-chain amino acids; resume when levels normalize
If possible, continue additional dietary support including lipids and formulas free of branched-chain amino acids
Hemodialysis may be necessary to remove toxic metabolites

17. Supplements, Formulas and Medications
Powdered protein supplements that are similar to whey protein
Leucine, isoleucine and valine removed
Major source of protein for patient
Ketonex makes an infant formula in powdered and liquid forms that are suitable for infants with MSUD
No medications available for specific treatment of MSUD
Isoleucine and valine may be supplemented back into diet

18. Case Study Anthropometrics: Born full term Born 7 lb 3 oz, 19 inches
Age: 3 years, 1 month
Height: 94 cm (37 in)  50th percentile
Weight: 14.3 kg (31.5 lb) 50th percentile
Length for weight: 75-90th percentile
Growth patterns have been consistently normal

19. Family and Social History
Patient lives with mother, step father, two older sisters (13 and 14 years of age) and three step- siblings (14 y/o male, two 12 y/o females)
Family receives WIC services and had an appointment scheduled with Early Intervention as of last visit
Insurance coverage through Medicaid; Children’s Special Services provides low protein foods and helps cover medical expenses if not covered by Medicaid

20. Family and Social History
Family seems to care for patient very well
Dad is literate and understands ROSS Family Guide booklet as well as need for diet changes
Feeds patient through G-tube
Mother attends G-tube clinic and changes is G-tube
Grandparents assist in care
Patient is enrolled in HeadStart
Receptive language increasing; says approximately six words

21. Prenatal History Normal Pregnancy!
Prenatal vitamin and iron supplement
Visited doctor regularly
Gained 30 lbs
No family hx of DM, heart disease or food allergies

22. Health History
Had problems with poor suckling and electrolyte imbalances
Received breast milk and Ketonex via NG tube due to his poor suck
Initiated thickened liquids and some solid foods but was not obtaining enough nutrients
PEG tube was placed to provide patient with nutrients due to dysphagia
As of most recent visit, mother reports dysphagia has resolved but no notation of latest swallow test; patient now with some PO intake but still with EN via PEG

23. Health History (cont) No food allergies
8 teeth on both top and bottom row
Current medications: isoleucine and valine
No mention of smoking or alcohol abuse in home
Activity level: cannot ride a tricycle; is able to partially dress himself; goes up and down the stairs;
No lifestyle modifications needed at this time as patient is at appropriate height and weight

24. Feeding Skills and Behavior
Will feed himself with his fingers but will not use a fork or spoon – there may be some fine-motor delay; may also have a language delay
Has full range of motion
Parenting skills are good
Advanced formula preparation

25. Eating Habits Good appetite
Eating more solid foods but is still dependent on PEG tube
Enjoys cereal, oatmeal and pizza

26. Present Intake Last food record: Evaluation of intake:
Captain Crunch, Kool-aide, chicken nuggets, fruit roll- up, apple juice, grape soda, cheese pizza, oatmeal
Evaluation of intake:
100% of kcal, 402% of protein, 148% of CHO
Isoleucine: 326 mg ( mg/day)100%
Leucine: 593 mg ( mg/day)111%
Valine: 396 ( mg/day) 100%

27. Biochemical Information
Most recent data:
Prealbumin: 18 mg/dl
Glucose: 68 mg/dl
Bicarb: 28 mEq/L
All normal!

28. Findings
ICD-9 Codes
270.3= MSUD
V44.1= G-Tube
Inadequate oral intake related to dysphagia and feeding difficulties as evidenced by majority of nutritional needs met through enteral feedings
Altered nutrient utilization related to inborn error of metabolism-MSUD as evidenced by hx of elevated leucine with restrictions needed to keep within range

29. Recommendations
Continue with current regimen of 125 g of Ketonex- 1, 55 g of Ketonex-2 and 32 g of Good Start, 3 ml of isoleucine and 6 ml of valine with water to total 40 ounces
Administer 5-8oz feedings throughout the day into PEG tube
Encourage low protein PO intake

30. Presenting Information to Family
No barriers noted in chart regarding literacy or ability to care for patient
All their ducks are in a row

31. Role of MNT Rationale for recommendations:
Dietary restrictions will limit branched-chain amino acids, specifically leucine
Prevention of toxic build-up of these amino acids and their metabolites
Enteral nutrition continued as we are unsure of dysphagia status and patient still has difficulty feeding himself
Maintain adequate calorie and protein intake to promote growth

32. Role of RD
To provide family and patient with support and recommendations regarding MNT
To modify the diet as needed to keep amino acids within target ranges
To act as a resource

33. References http://ghr.nlm.nih.gov/condition/maple-syrup-urine-disease
disorders/maple-syrup-urine-disease-msud
Diagnostics_of_MSUD.html