Paediatrics and Pregnancy Flashcards
Newborn screening encompasses more than just screening.
Screening
Follow-up
Diagnostic testing
Management
Program evaluation and quality assurance
How to select tests for newborn screening?
Modified Wilson and Jungner criteria
- suitable test available
- recognisable “latent” phase
- evidence for benefit to infant from early detection and management
- availability of efficacious diagnostic and clinical management program
- cost effective - cost of screening and management of outcome more cost effective than not screening
What is a suitable/ideal test method for newborn screening?
- validated methods available for screening and diagnosis
- amenable to dried blood spot testing
- high throughput with low cost
- multiple analytes/secondary targets detected by test method
- multiplex platform - LCMS/MS, HPLC, bead-based immunocapture, microarray
Most common amino acid/urea cycle disorder?
PKU 1:10 000
What is the most common enzyme deficiency in PKU?
Phenylalanine hydroxylase
How is PKU detected by newborn screening?
Tandem MS detection of increased phenylalanine and increased phenylalanine/tyrosine ratio
In general, how is newborn screening of amino acid/urea cycle disorders performed?
After dried blood spot sample collection, tandem MS quantification of amino acid/metabolite profiles with interpretation of disease specific patterns
Describe amino acid/urea cycle disorders
Autosomal recessive disorders of amino acid or protein metabolism, in which a specific enzyme defect causes accumulation of neurotoxic amino acids, metabolites or ammonia
Describe organic acid disorders
Autosomal recessive disorders due to a specific enzyme defect in the organic acid metabolic pathway, resulting in accumulation of organic acids in blood/urine
How are organic acid disorders detected by newborn screening?
Tandem MS quantification of acylcarnitines with interpretation of disease-specific profiles
What factors affect newborn screening of inborn errors of metabolism?
Feeding status, diet type, transfusion (PKU)
Describe the fatty acid oxidation disorders.
Autosomal recessive disorders causing specific enzyme defects in the fatty acid metabolic pathways which affect utilisation of dietary and stored fats
What is the risk associated with fatty acid oxidation disorders?
During illness or fasting, the inability to utilise fatty acids for energy results in hypoglycaemia. Death from first crisis in pts with MCAD is 1 in 4!
How is CAH detected in newborn screening protocols?
Detection of increased 17-OHP by DELFIA
List factors causing false positives and false negatives for CAH newborn screening
False positives:
- low birth weight
- prematurity
- physiologic stress
- day 1 17-OHP surge
False negatives:
- treatment with glucocorticoids prior to sample collection
How is newborn screening for congenital hypothyroidism performed?
Measurement of TSH on dried blood spot
Causes of congenital hypothyroidism
Athyreosis
Small, maldescended gland
Iodination defect
Clinical implications of hypothyroidism
Long term: Intellectual and physical disability
Short term: prolonged neonatal jaundice, feeding problems, FTT, constipation, lethargy, hypotonia, coarse facial features, thick tongue, hoarse cry, distended abdomen, umbilical hernia
Causes of false positives and negatives in newborn screening for hypothyroidism
False +ves: Very high TSH in first 24 hours of life, prematurity
False -ves: critically ill, premature, post-transfusion
What is galactosaemia?
An austosomal recessive disorder in which there is a deficiency of a specific enzyme required for conversion of galactose (from dietary lactose) to glucose. Accumulation of galactose in the blood causes organ toxicity
List the enzymes that may be deficient in galactosaemia. Which is the most common deficiency? Which of these enzyme deficiencies is detected by your state’s neonatal screening program?
GALT: Galactose-1-phosphate uridyltransferase (GUT) - the most common
GALK: Galactokinase
GALE: Uridine diphosphate-galactose-4-epimerase
In WA, GALT deficiency is screened for, however, GALK and GALE deficiency may be detected.
How is newborn screening for galactosaemia performed?
Detection of increased galactose and galactose-1-phosphate, and decreased GUT (galactose-1-phosphate uridyltransferase) activity on neonatal blood spot. Enzyme assay.
False negatives on galactosaemia testing may result from?
Extreme heat or delayed submission due to enzyme degradation
Baby not on milk feeds (do enzyme activity testing only)
Exchange transfusion (perform testing before transfusion)
Diagnostic testing for galactosaemia?
Genotyping. Could do plasma galactose and blood galactose-1-phosphate. RBC GUT activity.