Neonatal Screening

Question 1

WHO criteria for good screening tests

Answer 1

1. important condition
2. acceptable treatment available
3. facilities for diagnosis and treatment available
4. recognised latent or early symptomatic stage
5. suitable test or examination with high specificity and sensitivity
6. acceptable to population
7. balanced cost

Question 2

Traditional screening

Answer 2

Guthrie card - bacterial inhibition assay on a filter-paper blood spot (day 5 blood)
- qualitative, analytical variation

Quantitative determination by biochemical assays

Question 3

Phenylketonuria (PKU): cause, pathogenesis, presentations, treatment, suitability for screening

Answer 3

Very common in western population

Classical PKU = phenylalanine hydroxylase deficiency (phenylalanine to tyrosine)
Other causes of hyperphenylalaninaemia e.g. PTPS (tetrahydrobiopterin deficiency; PAH cofactor)
50:50 in HK

Excessive phenylalanine (5-10x normal) –> phenylketone side products (phenyl lactic acid/phenyl acetic acid) –> excreted in urine

Presentations:

• urine with a smell
• progressive irreversible neurological impairment if untreated (compete with essential a.a. to cross BBB)
• behavioural problems
• severity directly correlates with blood [phenylalanine]

Suitability for screening: dietary treatment would prevent severe mental retardation

Treatment and monitoring:
- dietary restriction of phenylalanine (but adequate)
- BH4 may boost PAH enzyme in some patients
- frequent blood Phe monitoring
(tyrosine supplements, other a.a., vitamins, minerals)

Question 4

Latest method of screening

Answer 4

Tandem mass spectrometry

• multiple metabolites (a.a. and acylcarnitines) assayed on one single test
• many countries started in early 2000s but HK only start in 2017

> 30 metabolic defects can be detected (FAOD e.g. MCAD, a.a. metabolic pathways e.g. PKU, organic aciduria e.g. GAI)

NBS for IEMs: Day 2 heel prick dried blood spot (previously use umbilical cord blood in HK)
–> in HK, very successful use of cord blood (efficient and economical) but not suitable for most inherited metabolic disease

Other methods:

• enzyme analysis e.g. galactosaemia
• immunoassay e.g. 17-OH progesterone for CAH

Question 5

Cord blood vs Dried blood spot

Answer 5

Cord blood

• taken at birth
• detects enzymes
• doesn’t detect metabolites (cleared by mother)
• detects DNA

Dried blood spot

• taken 2-3 days after birth (baby started own metabolic)
• detects enzymes, metabolites and DNA

Question 6

Other ongoing screening using umbilical cord blood: diseases and their manifestations, management

Answer 6

Congenital hypothyroidism

• defect in thyroid gland development
• most common preventable cause of mental retardation (1/4000)
• measure TSH, fT4 – TSH>15 mIU/L at cutoff (repeat on day 5)
• early (at 1-2 mths) and adequate T4 replacement = normal cognitive development
• follow up tests (re-evaluate at 3 yrs)

Glucose-6-Phosphate dehydrogenase deficiency

• X linked
• screening: measure enzyme activity (can’t detect all heterozygous females)
• 4.5% males, 0.3% females
• neonatal hyperbilirubinaemia due to haemolysis (kernicterus), food/drug/infection induced acute haemolysis, chronic haemolysis
• mostly asymptomatic throughout life (if not exposure to excessive oxidant stress)
• Mx: treat neonatal jaundice and haemolysis; avoidance unsafe drugs/chemicals e.g. naphthalene balls, beans, Chinese herbs; dietary restriction