15 - Newborn Screening

Question 1

Phenylketonuria (PKU)

Answer 1

• Hyperphenylketonuria associated with intellectual disability
• Permanent and irreversible
• First NBS implemented , with early detection, became a treatable disease

Question 2

Newborn Bloodspot Screening (NBS)

Answer 2

• Population screening program for genetic disease
• Targeted and treatable disorders of metabolism
• Bloodspot sample of 48-72 hours of age

Question 3

Tandem Mass Spectrometry (MSMS) in NBS

Answer 3

• Enabled screening for a large number of disorders difficult to detect
• Measures metabolic markers in an extract of a single bloodspot
• Enables second tier screening on selected samples

Question 4

Metabolic markers tested in MSMS

Answer 4

• Amino Acids
• Acylcarnitines

Question 5

Symptoms of PKU if untreated

Answer 5

• Microcephaly
• Mental retardation
• Seizures

Question 6

Inheritance of PKU

Answer 6

Autosomal recessive

Question 7

Congenital hypothyroidism symptoms if untreated

Answer 7

• Prolonged jaundice
• Feeding problems
• Umbilical hernia
• Mental retardation
• Hoarse cry

Question 8

Congenital hypothyroidism inheritance

Answer 8

Mainly sporadic

Question 9

CF symptoms if untreated

Answer 9

• Progressive respiratory disease
• Malabsorption
• Liver disease
• Diabetes mellitus

Question 10

Inhertiance of CF

Answer 10

Autosomal recessive

Question 11

Medium chain acyl-CoA dehydrogenase deficiency (MCAD)

Answer 11

• Most common fatty acid oxidation defect
• Requires MSMS for detection
• Hypoketotic hypoglycaemia
• Unscreened newborns at risk of permanent neurological deficit and death
• Easily treated

Question 12

Blood marker of MCAD

Answer 12

increased C8 acylcarnitine

Question 13

Spinal Muscular Atrophy (SMA)

Answer 13

• Affects the central and peripheral nervous system and skeletal muscle
• Detection of del exon 7 in SMN1 gene by qPCR of bloodspot DNA
• Deficiency of “survival of motor neuron”, SMN required for normal motor neurone function

Question 14

Inheritance of SMA

Answer 14

Autosomal recessive

Question 15

Severe Combined immune Deficiency (SCID)

Answer 15

• Absent or low T cells or B cells
• Susceptible to life threatening infection
• During T and B cell development, non replicating episomal circular DNA is formed
• Detection by qPCR of extracted TREC and KREC

Question 16

TREC

Answer 16

T cell receptor excision circles

Question 17

KREC

Answer 17

B cell kappa deleting recombination exicison circles

Question 18

Inheritance of SCID

Answer 18

X linked (most common) or autosomal recessive

Question 19

NBS process

Answer 19

1. Collection by midwives at 48-72h of age
2. Dry bloodspot and transport to NBS lab
3. Punch 3.2mm spots
4. qPCR, MSMS
5. If positive, second tier test to clarify
6. Recall for diagnostic testing

Question 20

Screening aims

Answer 20

• Select babies with increased risk of disease
• High sensitivity minimises false negative
• Recall affected newborn for diagnostic testing