MAPLE SYRUP URINE DISEASE

Brittany Taylor

Rebecca Linstead

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.

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

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

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

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

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

Genetic Inheritance

Autosomal recessive Each parent carries one normal copy and

one mutated copy of the gene but does not show symptoms themselves

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

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?

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

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)

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

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

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

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

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

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

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

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

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

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

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

Eating Habits

Good appetite Eating more solid foods but is still

dependent on PEG tube Enjoys cereal, oatmeal and pizza

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%

Biochemical Information

Most recent data: Prealbumin: 18 mg/dl Glucose: 68 mg/dl Bicarb: 28 mEq/L

All normal!

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

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

Presenting Information to Family No barriers noted in chart regarding

literacy or ability to care for patient All their ducks are in a row

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

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

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%20

cases/MSUD/Diagnostics_of_MSUD.html http://www.newbornscreening.info/Parents/aminoaciddisorders/MSUD.html