Download Risk Factors for Elevated Tyrosine (TYR) in MS/MS Newborn

Risk Factors for Elevated
Tyrosine (TYR) in MS/MS
Newborn Screening
Kimberly Cobb, MS RD LDN
Doctoral Student in Maternal & Child Health
University of North Carolina at Chapel Hill
North Carolina Newborn Screening
¢
NC uses tandem mass spectrometry
(MS/MS) to screen for >30 disorders
¢
Abnormal TYR considered >300µM
(until August 2002)
Transient Neonatal Tyrosinemia
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Hypertyrosinemia that peaks prior to 14
days and usually resolves by one month
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Likely due to decreased activity of 4hydroxyphenylpyruvic acid dioxygenase
(4HPPD)
¢
Proposed risk factors:
l
l
l
l
Prematurity
Excessive protein intake
Deficient vitamin C intake
Combination of above
(1) phenylalanine hydroxylase (tetrahydrobiopterin),
(2) tyrosine aminotransferase (TAT) (pyridoxine),
(3) 4-hydroxyphenylpyruvic acid dioxygenase (4HPPD) (ascorbate,
oxygen),
(7) & (8) the responsible enzymes have not been identified
From The Metabolic & Molecular Bases of Inherited Disease 8 th ed
Transient Neonatal Tyrosinemia
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Controversy over whether it is benign
Lethargy and reduced motor activity in
neonates
l Corneal opacities
l Intellect deficits in later childhood
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¢
No recent studies
Changes in feeding practices
l Changes in screening technology
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Study Aims
¢
Determine risk factors for transient
neonatal tyrosinemia.
Gender
l Race / ethnicity
l Type of feeding
l Birth weight (prematurity)
l Multiple births
l Age a specimen collection
l Other abnormal NBS labs
l
Methods
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Study Population
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Cases
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All infants screened by MS/MS in North
Carolina from August 1, 2001 to July 31,
2002
Infants with abnormal TYR (=300µM)
Controls
Infants with normal TYR (<300µM)
l Matched by laboratory batch of cases
l
Methods
¢
Descriptive, laboratory and follow-up
data was abstracted from the
Newborn Screening Database at the
NC State Laboratory of Public Health
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Logistic regression analysis was used
to determine the odds of having
abnormal TYR on a initial screen
Results
Table 1. Summary Statistics
Sample Size
Gender
Male
Female
Race
White
Black
Ethnicity
Non-Hispanic
Hispanic
Ave Age
Tyr Level
>500 µmol/L
300-500 µmol/L
Tyrosine Cases
482
Controls
861
48%
52%
52%
47%
48%
29%
53%
32%
55%
22%
48 hrs
64%
12%
45 hrs
11%
89%
0%
0%
Results
Table 2. Summary of Findings
Variable
Odds Ratio
Ethnicity
Hispanic
2.21
Birth Weight
Low Birth Weight
1.74
Very Low Birth Weight
1.59
Extremely Low Birth Weight
3.49
Feeding
Breastfeeding
2.73
Standard
Error
p-value
95% CI
0.58
0.003
(1.32, 3.71)
0.28
0.45
1.16
0.001
0.101
0.000
(1.26, 2.38)
(0.91, 2.75)
(1.92, 6.68)
0.48
0.000
(1.94, 3.84)
Adjusted for gender, age, transfusion, other abnormal labs, multiple births and death
Results
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Significant variables
Ethnicity
l Type of Feeding
l Birth Weight
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Results
¢
Non-significant variables
Gender
l Race
l Age at screen
l Transfusion
l Multiple births
l Infant Death
l Other abnormal labs (T4 / TSH)
l
Results
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Repeat screen requested for all infants
with abnormal tyrosine
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5% of repeat samples had TYR >300µM
1 infant with TYR II
l Several with liver disease
l Others resolved by time of confirmatory
testing
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Conclusions
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Breastfed infants may be catabolic in
neonatal period
l
¢
TYR elevations due to endogenous
sources of protein
Birth Weight
May be proxy for prematurity
l Need gestational age
l
¢
Unclear significance of Hispanic ethnicity
Changes in TYR Screening
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Cut off values for abnormal TYR
changed to >500µM in August 2002
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Number of abnormal TYR fell by 75%
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No known false negatives
Limitations / Future Studies
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Type of Feeding
l
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Relies on self-report
Gestational Age / Prematurity
Unavailable from NBS records
l Linkage to Birth Certificate Data
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Long-term effects of elevated TYR
Do they exist?
l At what level and duration do they occur?
l Implications for dietary treatment
l
Acknowledgements
This study has been made possible through the support of:
¢
Dianne Frazier, PhD MPH RD, Associate
Professor of Pediatrics, UNC-CH Department of
Pediatrics Division of Genetics and Metabolism
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NC State Laboratory of Public Health with special
thanks to
l Shu Chaing, PhD, Director of Newborn
Screening Program
l Susan Weavil, MS, Director of Tandem Mass
Spectrometry Laboratory