Maple Syrup Urine Disease

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 ketoaciddehydrogenase, 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 12-24 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: • 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 (165-325 mg/day)100% • Leucine: 593 mg (275-535 mg/day)111% • Valine: 396 (190-400 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 • http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2044.1996.tb12568.x/pdf • http://emedicine.medscape.com/article/946234-medication#2 • http://newenglandconsortium.org/for-professionals/acute-illness-protocols/organic-acid-disorders/maple-syrup-urine-disease-msud • http://www.wvdhhr.org/nbms/diseases/Maple_Syrup_Urine_Disease.asp • http://www.uic.edu/classes/phar/phar332/Clinical_Cases/aa%20metab%20cases/MSUD/Diagnostics_of_MSUD.html • http://www.newbornscreening.info/Parents/aminoaciddisorders/MSUD.html