1. Expanded Newborn Screening: The Nutrition Perspective
November 5, 2008
Beth Ogata, MS, RD

2. Nutrition Involvement in NBS
Policy
Diagnostic/coordination
Clinical
Community

3. Example: infant with galactosemia
Symptoms in newborn, if untreated
Vomiting, diarrhea
Hyperbilirubinemia, hepatic dysfunction, hepatomegaly
Renal tubular dysfunction
Cataracts
Encephalopathy
E. coli septicemia result
Death within 6 weeks, if untreated
Also
Duarte variant
galactokinase deficiency
uridine diphosphate-galactose-4-epimerase deficiency
Galactose-1-phosphate uridyl transferase (GALT) deficiency

4. Example: infant with galactosemia
Treatment: eliminate all galactose from diet
Primary source is milk (lactose= galactose + glucose)
Secondary sources are legumes
Minor? sources are fruits and vegetables
Food labels
milk, casein, milk solids, lactose, whey, hydrolyzed protein, lactalbumin, lactostearin, caseinate
Medications (lactose is often an inactive ingredient)
Dietary supplements
Artificial sweeteners
Monitoring: galactose-1-phosphate levels <3-4 mg/dl

5. Example: Infant with galactosemia
POLICY
RD participated on State Advisory Board to select disorders, including galactosemia
CLINICAL MANAGEMENT
RD provides nutrition care as member of the Biochemical Genetics Team:
Initiation of formula
Guidelines for monitoring intake
Plans for follow-up
RD as case manager
DIAGNOSIS & COOORDINATION
“Presumptive positive”  RD in contact with family and local providers to discuss appropriate feeding practices and arrange clinic appointment
COMMUNITY
RD at local health department provides ongoing education to family, local care providers

6. Nutrition and NBS: Policy
Screening process (disorders, procedures)
RD participated in Advisory Board meetings, providing input about nutrition-related treatment
Services and reimbursement
Nutrition consultant to state CSHCN Program
RD provides input about relevant state Medicaid policies
Training and education
RD provides information about management of metabolic disorders to local WIC agencies
Could be at a local/state/national level, or organizational

7. Nutrition and NBS: Clinical Management – PKU
Phenylketonuria
Phenylalanine hydroxylase
Dihydropteridine reductase
Biopterin synthetase
Establish diagnosis
Presumptive positive NBS results
> 3 mg/dL, >24 hrs of age
Differential diagnosis
 serum phe, nl tyr
r/o DHPR, biopterin defects
We’ll use PKU to illustrate the clinical management perspective

8. Current Treatment Guidelines
With effective NBS, children are identified by 7 days of age
Initiate treatment immediately
Maintain phe levels 1-6 mg/dl ( umol/L)
Lifelong treatment

9. Outcome Expectations
With NBS and blood phenylalanine levels consistently in the treatment range
Normal IQ and physical growth are expected
With delayed diagnosis or consistently elevated blood levels
IQ is diminished and physical growth is compromised

10. Clinical Management: PKU
Goals of Nutrition Therapy
Normal growth rate
Normal physical development
Normal cognitive development
Normal nutritional status

11. Clinical Management: PKU
Correct substrate imbalance
Restrict phenylalanine intake to normalize plasma concentration
Supply product of reaction
Supplement tyrosine to maintain normal plasma tyrosine levels
Phenylalanine //  Tyrosine
(substrate) phenylalanine hydroxylase (product)

12. Goals of Nutrition Support for Phenylketonuria (PKU)
Maintain plasma phenylalanine (phe) between 1-6 mg/dl
Without PKU, phe ~ 1.0 mg/dl
Maintain plasma tyrosine (tyr) between 0.9–1.8 mg/dl
Normal = mg/dl
A little bit of background, to help explain the case

13. Goals of Nutrition Support for Phenylketonuria (PKU)
Interpretation of phenylalanine levels
~1 mg/dl
Normal
1-6 mg/dl
Excellent
6-10 mg/dl
Good
10-15 mg/dl
Caution
15-20 mg/dl
Dangerous
> 20 mg/dl
Very damaging

14. Phe Levels from NBS to Tx
Equilibrium achieved by
14 days of age
Diagnostic levels
Blood levels every 2 days
because of rapid growth

15. Adjustments necessary to maintain “safe” blood phe levels
Usual intake of phe
Newborn on formula
20 oz x 22 mg phe/oz = 440 mg phe
1 yo child on “regular” diet
30 g protein = 1500 mg phe (DRI = 13.5 g)
7 yo child on “regular” diet
50 g protein = 2500 mg phe (DRI = 19 g)
Phenylalanine requirement
250 mg/d

16. Management Tools Specialized formula provides
80-90% energy intake
89-90 % protein intake
tyrosine supplements
no phenylalanine
Phenylalanine to meet requirement from infant formula or foods

17. Formula Composition Regulated by FDA Designated by clinician
Renal solute load
Carbohydrate source
Fat source
Amino acid source
Vitamin and mineral content
Designated by clinician
Protein/energy ratio
Specific amino acid
Fluid balance
Total protein
Total energy

18. Effect of a single amino acid deficiency on growth

19. Food Choices for PKU

20. Sample Menu: ~1 year old Total Protein: 32.5 grams (1625 mg phe)
Food
Protein (g)
¼ cup Cheerios
0.8
½ banana
0.6
½ cup milk 4
2 graham crackers 2
¼ tuna sandwich 8
½ peach
2 saltines
¼ cup juice
¼ cup cottage cheese 7
¼ cup green beans
0.3
TOTAL
32.5
>>1625 mg phe
Total Protein:
32.5 grams
(1625 mg phe)
DRI (protein):
13.5 grams (~675 mg phe)
Phe requirement:
250 mg

21. Sample Menu: ~1 year old
Food
Protein (g)
¼ cup Cheerios
0.8
½ banana
0.6
½ cup milk 4
2 graham crackers 2
¼ tuna sandwich 8
½ peach
2 saltines
¼ cup juice
¼ cup cottage cheese 7
¼ cup green beans
0.3
TOTAL
g protein
>> mg phe
To meet 250 mg phe  minus milk, tuna, cottage cheese:
Total Protein:5.5 g
Is this adequate protein to support growth?
Is this adequate energy to support growth?
What about adequacy of other nutrients?

22. Tools of Management: Low protein food products
Phe content of regular products
Phe content of low protein products
Rice
300 mg/cup
LP rice
23 mg/cup
Pasta
163 mg/cup
LP pasta
5 mg/cup
Bread
105 mg/slice
LP bread
10 mg/slice
Cheerios
93 mg per ½ cup
LP Loops
5 mg per ½ cup
Saltines
65 mg/5 crackers
LP saltines
3 mg/5 crackers
Potatoes
145 mg/cup
REORODER THESE

23. Typical Food Pattern for a Child with PKU
1 year old, weight & length at 50th %ile for age
Energy needs: kcal
Protein needs: 20 g
Phenylalanine needs: 250 mg
Formula prescription:
Phenyl-Free: 125 g
Similac pdr: 50 g
Water to 40 oz
Food prescription:
25 mg phe, 200 kcal, 0.5 g protein

24. Monitoring Adequacy of Treatment
Measure plasma amino acids
Maintain in treatment range
Monitor nutrient intake
Restrict phenylalanine, supplement tyrosine, adequate protein, energy, other nutrients to support growth and ensure good health
Monitor growth increments
Typical growth expected
Monitor cognitive development
Typical achievement expected

25. Effective Blood Level Management in Childhood
Blood levels once per month, or more frequently if needed for good management

26. PKU Management Guidelines Self-management Skills

27. Goal of Lifetime Management of PKU
To maintain metabolic balance while providing adequate nutrients and energy for normal physical and intellectual growth

28. Maternal PKU Concerns/Outcomes
Women with PKU are at high risk for delivering a damaged infant
Placenta concentrates phe 2-4x
Microcephaly
Cardiac problems
Infant IQ directly related to maternal blood phe level
Outcome improved with maternal blood phe <2 mg/dl prior to conception and during pregnancy

29. Nutrition and NBS: Community – Glutaric Acidemia, type I
Defect in lysine and tryptophan catabolism
Treatment:
LYS- and TRP- restriction (specialized formula, low protein food pattern)
Riboflavin
Frequent monitoring
Aggressively prevent catabolism  metabolic crisis
Symptoms:
Macrocephaly, frontotemporal atrophy and delayed myelination
Myoclonic seizures, ataxia, choreoathetosis
Intermittent metabolic acidosis
Example of interdisciplinary, interagency collaboration
Glutaryl-CoA dehydrogenase deficiency

30. Example: Infant with GAI
12 month old
Medical conditions:
Glutaric acidemia, type 1 (identified by NBS)
Cystic fibrosis
Meconium ileus (repaired)
GER
Goals: optimal nutrition status, avoid metabolic decompensation
Simplified nutrition-related history
Breastmilk (or Isomil)+ Glutarex-1 to restrict lysine
MCT oil, concentrated formula for weight gain; pancreatic enzymes
Solid foods introduced when developmentally appropriate
NG tube  g-tube placed by 2 mo

31. Example: Infant with GAI
“The Players”
Family:
mother, father, infant, extended family
Biochem team:
geneticist, nutritionist, genetic counselor
Pulmonary team:
pulmonologist, nutritionist, social worker, nurses
Primary care:
pediatrician
Community:
therapists, WIC nutritionist, public health nurse, home infusion company

32. Example: Infant with GAI
MNT and monitoring plan:
Formula – preparation, “recipe,” tolerance
Blood levels – schedule, lag between draw and results
Growth and nutrient needs – balance approaches for CF and GA1
Food – introduction of solids, oral aversion
Prioritization
Communication

33. Nutrition and NBS: Community
PHN and interpreter make monthly visits to family of young child with MSUD.
Through pre-arranged phone calls, we can discuss formula composition and preparation, and solid foods.
This helps provide information between regular clinic visits.
Other examples of community-level involvement

34. Nutrition and NBS: Community
A woman with PKU is enrolled in te First Steps program (WA State MSS)
The RD with PKU Clinic provides consultation to the First Steps RD, about management of amino acid levels.
Other examples of community-level involvement

35. Nutrition and NBS: Community
The family of a child with propionic acidemia receives formula from home infusion company.
The home infusion RD is able to make home visits to evaluate growth and intake, and communicates with clinic RD.
This helps to ensure that the family is able to implement recommendations.
Other examples of community-level involvement

36. Nutrition and NBS: Community The baby has a “positive PKU test”
What were the blood phenylalanine (phe) or other critical elevated blood levels?
When was the sample collected?
What is the protocol for confirming the diagnosis?
When was the diagnosis made?
Did this referral come from a screening test? If so, what is the next step toward diagnosis?
Is the family aware of the results?

37. Information Needed by Community and Metabolic Teams Before MNT is Initiated
If an infant has been identified by NBS:
Which NBS results are positive
Birth date and age of the infant
Birth weight and gestational age
Current weight
Current form of feeding, and intake
Current health status of the infant

38. Critical Questions about Follow-up and Coordination of Treatment
Who is your contact at the metabolic center?
What is the recommended treatment for the disorder?
What nutrition intervention is required? How is this monitored?
What is the mechanism for follow-up and testing?
Who will prescribe the specialized formulas?
How will the community and metabolic teams communicate about intervention?

39. The Team Child Age-appropriate self-mgmt skills Parents
Health status monitoring, teaching, advocacy
Nutritionist
MNT, feeding skills
Geneticist
Medical monitoring
Lab
Laboratory monitoring
Medical Home
Well Child Care, family support
Psychologist
Developmental monitoring, screening
Community Providers (RD, PHN)
Family support in community
School
Educational programs, tx monitoring
Therapists (OT, PT, SLP, etc.)
Developmental monitoring and intervention
Good communication is critical
Complex disorders that require prescise management

40. NBS and the Community: Challenges
Understand the implications of the results of newborn screening tests
Develop a communication system between the community providers and the metabolic team for support of treatment
Interact with PCPs and families as needed, to support appropriate MNT

41. NBS and the Community: What you need to know
Which disorders are identified by NBS in your state? Where do you find this information?
What is the difference between screening and diagnostic results?
What is the system for follow-up of presumptive positive NBS results?
How do you make referrals to regional genetics clinics and specialty care clinics?
Screening tests are meant to identify individuals with an incresed probability of having a specific disorder…. More from PNPG POST

42. Caveats to Ponder Is it really a disorder? What are we talking about?
Is GA1 really so different than GA2?
If we’re out of MSUD Analog, can we use MSUD Maxamaid?
Screening vs. diagnosis
Is it really PKU?
Several of the metabolic abnormalities may not require immediate intervention and some may not require intervention at all.
An infant with presumed 3-methylcrotonyl-CoA carboxylase deficiency will require a diagnostic workup but may be mildly affected and not require intervention.
Names of many disorders are similar and can be easily confused.
Glutaric acidemia type I (deficiency of glutaryl-CoA dehydro­genase) and glutaric acidemia type II (multiple acyl-CoA dehydrogenase deficiency) may require similar nutritional intervention but have quite different metabolic abnormalities and consequently differing outcomes.
Many formulas have similar names and may be confused.
A community RD was asked to order MSUD Maxamaid® for a newborn with maple syrup urine disease. The order should have been for MSUD Analog* which is a formula designed for infants with MSUD.
Each positive screening result must be followed-up to confirm or deny the diagnosis of the specific disorder.
It has become common usage to call the newborn screening tests “the PKU test”.
This terminology is misleading because NBS programs screen for an array of disorders
If informed that an infant has “a positive PKU test” it is important to be sure that PKU is the disorder that has been “flagged” by NBS.
It is often believed that “the PKU test” provides a diagnosis rather than an indication for diagnostic studies.
These tests should always be termed “newborn screening”.

43. Scenes from the Annals of Reporting and Acting on NBS Results
A primary care physician telephones are reports there is a new baby with PKU and asks that you please start the infant on formula ASAP.
What additional information do you need?
What would you do?

44. Scenes from the Annals of Reporting and Acting on NBS Results
You are on-call for the weekend for your local hospital and you receive an order from the newborn nursery on an infant with presumptive galactosemia and a request for the initiation of treatment.
What additional information do you need?
What would you do?

45. Additional Information
Washington State Newborn Screening
Star G-Screening, Technology, and Research in Genetics
National Newborn Screening and Genetics Resource Center
Building Block for Life Volume 27, No 1. Pediatric Nutrition Practice Group (Expanded NBS)
Building Block for Life Volume 30, No 3. Pediatric Nutrition Practice Group (Genetics and Expanded NBS)