methodology results amino acid levels in newborns a pilot study on an expanded newborn screening...
TRANSCRIPT
Methodology
Results
Amino Acid Levels in Newborns
A Pilot Study on an Expanded Newborn Screening Program in Palestine
Samir Khatib , Amer AyyadMedical School / Al-Quds University
Introduction
Newborn screening is a universal health program which is useful in the early
detection of serious metabolic and genetic diseases in newborns before
symptoms begin to appear. Until this day newborns in Palestine are being
screened for phenylketonuria and congenital hypothyroidism only. However,
a number of other metabolic diseases have been recognized amongst the
population, including amino acid and urea cycle disorders. Therefore, the
study was conducted in an effort investigate the possibility of finding such
cases in newborns throughout the West Bank of Palestine. The study was
conducted in collaboration with the Palestinian Ministry of Health through the
collection of samples, and the Human Genetics Department at Liege
University in Belgium by analysing the samples.
Study objectives
*To assess the need for expanding the existing newborn screening program in Palestine.
*To investigate the relationship between some demographic variables such as
gender, kinship, district, weight and amino acids levels.
*To determine the reference ranges for a number of amino acids and urea cycle
intermediates in Palestinian newborns.
A cross-sectional observational study design was done. The study covered all
12 districts of the West Bank in Palestine during the period between January
2012 and January 2013 . A pilot study was done before the actual study took
place. Convenience sampling was used to recognize the study participants of
newborns. Blood samples were collected on special blood collection cards.
Information regarding weight, date of birth, sex , district, and kinship of parents
was taken. Number of samples was 4240 and informed consent was taken
from each parent participant. Analysis of amino acids and urea cycle
intermediates was done using tandem mass spectrometry (MS/MS) .
Introduction and Study objectives
Amino Acids Amino Acids Lower limit Lower limit (µmol/L)(µmol/L)
Upper limit Upper limit (µmol/L)(µmol/L)
MeanMean Std. DeviationStd. Deviation
Phenyalanine 34.9 79.7 53.31 11.24
Tyrosine 60.2 201.3 114.99 35.54
Methionine 11.7 27.9 18.52 4.19
Leucine-Isoleucine 127.0 336.0 208.95 52.72
Valine 82.2 206.3 131.46 30.96
Citrulline 9.3 26.2 15.78 4.30
Argininosuccinate 0.2 0.8 0.43 0.16
Arginine 4.8 28.5 12.95 6.19
Asparagine-Ornithine 57.5 244.9 121.52 46.86
Reference ranges of amino acids based on Non parametric percentile method(CLSI C28-A3)
Amino Acid Amino Acid NormalNormal AbnormalAbnormal TotalTotal
Count Row N % Count Row N % Count Row N % Phenylalanine 4105 96.8% 134 3.2% 4239 100%
Tyrosine 4081 96.3% 158 3.7% 4239 100%
Methionine 4076 96.2% 163 3.8% 4239 100%
Leucine-Isoleucine 4068 96.0% 171 4.0% 4239 100%
Valine 4076 96.2% 163 3.8% 4239 100%
Citrulline 4069 96.0% 170 4.0% 4239 100%
Argininosuccinate 4089 96.5% 150 3.5% 4239 100%
Arginine 4069 96.0% 170 4.0% 4239 100%
Asparagine-Ornithine 4076 96.2% 163 3.8% 4239 100%
Conclusions
*Based on our established reference ranges for each analyte the results showed that 22.5% of the tested samples (955) had at least one amino acid
level in the upper 2.5% of the population.
* There is a significant relationship between mean weight and gender.
*There is a significant relationship between mean weight and some amino acids levels.
*Neither gender nor kinship had any effect on the amino acid level, but there is a significant difference between some amino acids mean and gender.
*There is a significant difference between some amino acids levels and districts.
* The study results support further assessment of the need to expand the existing newborn screening program in Palestine.
Contact information
Status of Abnormal Amino Acid Levels in Newborns
Amino Acid GenderN Mean Std. Deviation
Std. Error Mean
P-Value by independent
sample T-TestPhenylalanine Female 2104 53.73 14.43 0.31
.714Male 2135 53.88 12.56 0.27Tyrosine Female 2104 119.11 41.44 0.90
.002Male 2135 115.23 39.39 0.85Methionine Female 2104 18.99 4.82 0.11
.034Male 2135 18.66 5.10 0.11Leucine-Isoleucine Female 2104 211.14 58.29 1.27
.065Male 2135 214.62 64.16 1.39Valine Female 2104 134.31 34.16 0.74
.180Male 2135 132.84 37.28 0.81Citrulline Female 2104 16.39 5.67 0.12
.090Male 2135 16.09 5.88 0.13 Argininosuccinate Female 2104 0.44 0.18 0.00
.302Male 2135 0.45 0.19 0.00 Arginine Female 2104 13.03 7.04 0.15
.000Male 2135 13.83 7.65 0.17 Asparagine-Ornithine Female 2104 124.43 62.77 1.37
.289Male 2135 126.36 55.82 1.21
Relationship between Gender and Mean Amino Acid Levels
Amino Acid Test Mean WeightP-Value by Independent
sample T-Test Phenylalanine Normal 3.23
0.718Abnormal 3.22 Tyrosine Normal 3.23
0.011Abnormal 3.13
Methionine Normal 3.23
0.214Abnormal 3.18 Leucine-Isoleucine Normal 3.24
0.001Abnormal 3.11
Valine Normal 3.23
0.193Abnormal 3.18 Citrulline Normal 3.23
0.52Abnormal 3.21 Argininosuccinate Normal 3.23
0.852Abnormal 3.22 Arginine Normal 3.23
0.367Abnormal 3.26 Asparagine-Ornithine Normal 3.23
0.06Abnormal 3.16
Relationship between Mean Weight and Amino Acid Levels
Relationship between District and Phenylalanine Level
Relationship between District and Citrulline Level
Relationship between District and Arginine Level
Relationship between District and Asparagine-Ornithine
Level
Samir Khatib, Genetics and Metabolic Diseases Center,
Alquds University Medical School, Abu Dis, Jerusalem, Palestine.
[email protected]. NOTE: The authors disclose
no conflict of interest.