Kuwait has expanded its newborn screening program to screen for 22 primary disorders including 18 inborn errors of metabolism, 2 endocrine disorders, and 2 other metabolic disorders. The expanded screening provides benefits like early identification and intervention to reduce morbidity and mortality. Screening is done through heel prick samples that are tested at the Newborn Screening laboratory. Positive results require confirmatory testing while negative results are sent to hospitals. The expanded screening aims to improve outcomes for treatable genetic disorders.

1. Newborn Screening:
Kuwait’s Expanded Screening
Program
Prepared by:
Dr . Amir Abdelazim Ahmed
clinical pathology specialist
at Kuwait medical Genetic Center

2. Newborn Screening – What’s
new?
 Previously:
◦ PKU, congenital hypothyroidism
 At 31 October 2014 :
◦ Progressive expansion to 22 primary disorders
◦ NBS includes metabolic and endocrine conditions

3. Expanded NBS – 22 conditions
 18 inborn errors of metabolism
 2 endocrine disorders
◦ Congenital hypothyroidism
◦ Congenital adrenal hyperplasia
 2 other metabolic disorders
◦ Galactosemia
◦ Biotinidase deficiency

4. Benefits of NBS
Identification
Early intervention
Reduced morbidity & mortality
Family planning

5. Risks of NBS
 Parental anxiety (false positives)
 Missed diagnosis (false negatives)
 The right ‘not to know’
 Unanticipated outcomes
 Labelling – diagnosis of benign
conditions

6. NBS: how & where is it done?
 Method: Heel prick
 Sample collection: newborn screening card
collected by staff of each hospital
 Testing Location: Newborn Screening
laboratory at KMGC
 Transportation: NBS cards are sent from
all hospitals via special drivers

7. Timing of Testing
 Acceptable samples
◦ between 1 day (24 hours) and 7 days after birth
 Best time for sample:
◦ between 2 days (48 hours) and 3 days (72 hours)
after birth
 If tested before 1 day (24 hours) of age,
REPEAT the test within 5 days
 If the baby is >5 days, screening is still
available
◦ Show Kuwait NS-protocol for details

8. Special Considerations
 Prematurity
If <33 weeks - collect three specimens at 2,14and 30 days old
◦ Indicate this on NBS card (1st , 2nd , 3rd )
◦ Premature may have false positive test results
 Total Parenteral Nutrition (TPN)
◦ Certain amino acids and organic acids will be elevated
◦ Indicate this on NBS card
 Transfusion
◦ Disorders may be missed
◦ Ideally complete card and obtain sample before transfusion
 Early discharge
◦ If prior to 24 hours, parents should be informed that a
repeat sample must be done and hospital give him referral
for 2nd sample time

9. The Heel Test

10. Sample
qualitative
validity

11. NBS
Report

12. Screen Positive Results
 Screen positive means:
◦ Further testing is required to confirm the diagnosis
◦ Does NOT mean that the infant is affected
 NSO will immediately notify parents and
arrange confirmatory testing
 If diagnosis is confirmed, cases refere to
specialist for treatment & follow up
 Report will be mailed to NSO at hospital
according to the parent address , provided that
correct information is completed on the screening
card.

13. Results of Expanded NBS by
MS/MS
Schulze et al. Pediatrics 2003
 250,000 neonates screened for 23 inborn
errors of metabolism
◦ 106 newborns with confirmed metabolic disorder
 70 required treatment
◦ Overall prevalence of metabolic disorder = 1/2400
◦ 825 false positives (0.33% false positive rate)
◦ Overall specificity = 99.67% (PPV = 11.3%)
◦ Overall sensitivity = 100% for classic forms of
disorders
 = 92.6% for variants
◦ 61 /106 were judged to have benefited from
screening and treatment
 58% of true positives
 1/4100 newborns

14. Negative Results
 Results will go to:
◦ Submitting health care professional/hospital
 If you suspect that an infant or child has
symptoms of a screened condition and their
NBS results are negative – please refer to
the appropriate specialist for evaluation
◦ NBS panel does not screen for every metabolic condition
◦ NBS is a screening test – not diagnostic

15. Expanded NBS – 22 conditions
 18 inborn errors of metabolism
◦ 7 organic acid disorders
◦ 5 fatty acid oxidation disorders
◦ 6 amino acid disorders
 2 endocrine disorders
 2 other metabolic disorders

16. Inborn errors of metabolism
 Rare
 Usually autosomal recessive inheritance
◦consanguinity is more common
 Symptoms secondary to a problem in the
metabolic pathway
 Usually not significant dysmorphism
 Early recognition and intervention can be
lifesaving

17. Organic Acid Disorders
 Isovaleric acidemia (IVA)
 Glutaric acidemia type 1 (GA1)
 Multiple carboxylase deficiency (MCD)
 Methylmalonic acidemia (MMA)
 3-methylcrotonyl-CoA carboxylase (3MCC)
deficiency
 Propionic acidemia (PA)
 Β-ketothiolase deficiency (BKT)

18. Organic Acid Disorders
 What are organic acid disorders?
◦ Body cannot metabolize certain amino acids and fats
◦ Accumulation of organic acids in blood and urine
◦ Serious potentially preventable effects on health and
development, including death
 Symptoms
◦ acute encephalopathy, vomiting, metabolic acidosis,
ketosis, hyperammonemia, hypoglycemia, coma
◦ dehydration, failure to thrive, hypotonia, global
developmental delay
◦ sepsis, death
 Treatment
◦ Low protein diet / restrict amino acids,
◦ Supplements: carnitine, biotin, riboflavin, glycine
◦ Avoid fasting

19. Fatty Acid Oxidation Disorders
 Medium-chain acyl-CoA dehydrogenase
(MCAD) deficiency
 Very long-chain acyl-CoA dehydrogenase
deficiency (VLCAD)
 Long-chain L-3-OH acyl-CoA
dehydrogenase deficiency (LCHAD)
 Trifunctional protein deficiency (TFP)
◦ catalyzes 3 steps in mitochondrial beta-
oxidation of fatty acids
 3-Hydroxy-3-methylglutaryl-CoA lyase
def.(3HMG)

20. Disorders of Fatty Acid Oxidation
 What are disorders of fatty acid oxidation?
◦ Breakdown of fatty acids in mitochondria is an essential
part of body’s ability to produce energy
◦ Disorder: inability to break down fatty acids
 Symptoms
◦ Decompensate with any catabolic stress
 fever, fasting, intercurrent illness
◦ Hypoketotic hypoglycemia, liver, muscle, heart disease
◦ Lethargy, seizures, coma, sudden death (SIDS)
 Treatment
◦ Avoid fasting
◦ IV glucose when ill to prevent hypoglycemia
◦ Frequent feeding

21. Amino Acid Disorders
 Phenylketonuria (PKU)
 Maple syrup urine disease
(MSUD)
 Tyrosinemia type 1 (TYR 1)
◦Common in French Canadians
 Homocystinuria (HCY)
 Citrullinemia (CIT)
 Argininosuccinic acidemia (ASA)

22. Amino Acid Disorders
 What are amino acid disorders?
◦ Occur when the body cannot either metabolize or
produce certain amino acids
◦ Result in toxic accumulation of substances
◦ Serious potentially preventable effects on health and
development including death
 Symptoms (untreated) example PKU
◦ Hyperphenylalaninemia (neurotoxic)
◦ Microcephaly, epilepsy, mental retardation, behaviour
problems
 Treatment
◦ Diet: reduce phenylalanine, low protein, supplement
cofactors or essential amino acids

23. Expanded NBS – 22 conditions
 18 inborn errors of metabolism
◦ 7 organic acid disorders
◦ 5 fatty acid oxidation disorders
◦ 6 amino acid disorders
 2 endocrine disorders
 2 other metabolic disorders

24. Endocrine Disorders: CH
Congenital Hypothyroidism (CH)
 What is CH?
◦ inadequate thyroid hormone production
◦ Anatomic defect in gland, dyshormogenesis, iodine
deficiency
 Symptoms
◦ MR, ↓ growth & bone maturation, neurologic problems:
spasticity, gait abn, dysarthria, autistic behaviour
 Treatment
◦ Diagnosis made before 13 days to prevent symptoms
◦ Thyroid hormone replacement

25. Endocrine Disorders: CAH
Congenital Adrenal Hyperplasia (CAH)
 What is CAH?
◦ Impaired synthesis of cortisol by the adrenal cortex leads to
↑↑↑ androgen biosynthesis
◦ Inability to maintain adequate energy & blood glucose level
to meet stress of injury & illness
 Symptoms
◦ Virilization (♀ ambiguous genitalia), precocious puberty,
infertility, short stature
◦ Renal salt wasting leads to FTT, vomiting, dehydration,
hypotension, hyponatremia, & hyperkalemia
 Treatment
◦ Glucocorticoid replacement therapy

26. Expanded NBS – 22 conditions
 18 inborn errors of metabolism
◦ 7 organic acid disorders
◦ 5 fatty acid oxidation disorders
◦ 6 amino acid disorders
 2 endocrine disorders
 2 other metabolic disorders

27. Other Disorders:
Biotinidase deficiency
 What is biotinidase deficiency?
◦ Biotinidase is responsible for recycling biotin – a cofactor for
4 dependant carboxylases
 Symptoms
◦ Metabolic ketoacidosis, organic aciduria, mild
hyperammonemia
◦ Seizures, hypotonia, ataxia, developmental delay, vision
problems, hearing loss, cutaneous abnormalities
 Treatment
◦ 5-10mg of oral biotin per day, long term treatment prevents
all symptoms

28. Other Disorders: Galactosemia
 What is galactosemia?
◦ Lactose is main sugar in breast milk & infant formulas
◦ Metabolized into glucose and galactose in the intestine
◦ Unable to break down galactose
 Symptoms
◦ Feeding problems, FTT, bleeding, infection, liver failure,
cataracts, mental retardation, death
 Treatment
◦ Lactose-galactose-restricted diet
 must be started in first 10 days of life to prevent symptoms
◦ Even with treatment - ↑ developmental delay, speech
problems, abn motor function, premature ovarian failure

30. References
Ontario newborn screening guideline protocol
National Newborn Screening & Global Resource Center
http://genes-r-us.uthscsa.edu/