Lecture 32: Newborn screening

Question 1

What is screening?

Answer 1

Screening is a process of identifying apparently healthy people who may be at increased risk of a disease or condition. They can then be offered information, further tests and/or treatment to reduce their risk and/or complications.

Question 2

True or false: Screening is 100 % sensitive and specific

Answer 2

False

Question 2

True or false: Screening is 100 % sensitive and specific

Answer 2

False

Question 3

What are the 5 principles of the Wilson and Jungner criteria?

Answer 3

1.Disease must be sufficiently common
2.Natural history must be known
3.Early therapeutic intervention beneficial
4.Acceptable and affordable screening test
5.Diagnostic confirmatory test

Question 4

When are babies first tested after birth?

Answer 4

5 days (5-8 exceptional)

Question 5

Summarise new-born screening in the UK:

Answer 5

Most samples taken in community by midwives

Regional laboratories perform tests and report results

Standards set by The UK Newborn Screening Programme Centre

Nature of the programme defined by The National Screening Committee

Question 6

What type of sample is taken at a screening early on?

Answer 6

Blood spot test

Question 7

For positive babies, how quickly is it expected for babies to be on treatment with referral?

Answer 7

Within 3 days

Question 8

What happens if a baby identified as missed?

Answer 8

A blank screening blood spot test is sent off

Question 9

What does the new-born screening screen for?

Answer 9

-Congenital hypothyroidism
-Sickle cell and Hb disorders
-CF (cystic fibrosis)
-PKU (phenylketonuria)
-MCADD (medium chain acyl -CoA dehydrogenase deficiency)
-MSUD (maple syrup urine disease)
-IVA (isovaleric acidaemia)
-Homocystinuria – non-pyridoxine responsive
-GA1 (glutaric aciduria type 1)

-SCID (severe combined immunodeficiency)
(pilot in six laboratories)

Question 9

What does the new-born screening screen for?

Answer 9

-Congenital hypothyroidism
-Sickle cell and Hb disorders
-CF (cystic fibrosis)
-PKU (phenylketonuria)
-MCADD (medium chain acyl -CoA dehydrogenase deficiency)
-MSUD (maple syrup urine disease)
-IVA (isovaleric acidaemia)
-Homocystinuria – non-pyridoxine responsive
-GA1 (glutaric aciduria type 1)

-SCID (severe combined immunodeficiency)
(pilot in six laboratories)

Question 10

What is Phenylketonuria?

Answer 10

A genetic condition that causes increased levels of phenylalanine (an amino acid) in the body.

Question 11

How rare is PKU?

Answer 11

Affects 1: 10,000 Caucasian births

Question 12

How does it affect a baby if untreated?

Answer 12

Severe intellectual disability
(Excellent prognosis if treated from birth)

Question 13

What is the screening test for PKU?

Answer 13

Screening test: bloodspot phenylalanine

Confirm diagnosis with plasma phenylalanine measurements
no need to measure enzyme or DNA

Question 14

How does newborn screening in the UK differ from other countries?

Answer 14

Profile of diseases
Day of life of test
Not always provided by the state

Question 15

5 things found in the history of untreated PKU?

Answer 15

Severe intellectual disability
seizures, tremors
spasticity
behavioural problems, irritability
eczema in childhood

Question 15

5 things found in the history of untreated PKU?

Answer 15

Severe intellectual disability
seizures, tremors
spasticity
behavioural problems, irritability
eczema in childhood

Question 16

How do you treat PKU?

Answer 16

1. Low phenylalanine diet
   (Requires careful monitoring
   Risk tyrosine insufficiency
   Risk vitamin and trace element deficiencies)
2. biopterin supplementation (sapropterin)
   (Kuvan (recently approved by NICE for certain patients, starting imminently))

Question 17

What is congenital Hypothyroidism?

Answer 17

Congenital hypothyroidism (CH) is thyroid hormone deficiency present at birth. If untreated for several months after birth, severe congenital hypothyroidism can lead to growth failure and permanent intellectual disability.

Question 18

How many people does congenital Hypothyroidism affect?

Answer 18

Affects 1: 1,500 UK births

Question 19

How is congenital hypothyroidism treated?

Answer 19

Treatment with thyroxine, carefully monitored

Question 20

How is congenital Hypothyroidism screened for?

Answer 20

Screening test: bloodspot TSH
Confirm diagnosis with plasma thyroid function tests

Question 21

What is MCADD?

Answer 21

Autosomal recessive inherited defect of fatty acid oxidation

Body cannot use its own fat reserves to produce energy in periods of fasting or metabolic stress

Hypoglycaemia and metabolic decompensation develop, which may result in seizures, brain damage or death

Question 22

What is screened for when investigating MCADD?

Answer 22

Screening test: bloodspot C8 and C8/C10 ratio Confirmation of diagnosis: Bloodspot acylcarnitines, urine organic acids, DNA analysis

Question 23

What is the prognosis of MCADD if treated?

Answer 23

Prognosis: good if decompensation avoided. ‘Safe’ times between meals increases as children grow older

Question 24

How is MCADD treated?

Answer 24

Avoidance of fasting

Question 25

How many births does MCADD affect?

Answer 25

Affects 1:10,000 UK births

Question 26

What is Cystic fibrosis?

Answer 26

A genetic disorder, in which the lungs and the digestive system get clogged with mucus.

Question 27

How many births does CF affect?

Answer 27

Most common inherited, 1:2,500

Question 28

Why was screening for CF initially controversial?

Answer 28

Not all cases detected by IRT-DNA protocol Doubts about clinical benefits of early treatment Identification of less severe variants Identification of heterozygotes

Question 29

What is the treatment for CF?

Answer 29

New drugs for CF will revolutionise treatment Modulator therapy – drugs which modulate the function of the CFTR protein, allowing it to work more effectively These include drugs such as ivacaftor, elexacaftor and tezacaftor

Question 30

What is sickle cell disease?

Answer 30

An inherited blood disorder where red blood cells (RBCs) become sickle/crescent shaped. It causes frequent infections, swelling in the hands and legs, pain, severe tiredness, and delayed growth or puberty

Question 31

What can be detected in relation to haemoglobinopathies in a screening?

Answer 31

detect carriers and compound heterozygotes with HbC/DPunjab/E/OArab/β-thal β-thalassaemia major detected

Question 32

How many births are affected by sickle disease?

Answer 32

Sickle disease affects 1:2000 babies (up to 1 in 300)

Question 33

What happens if sickle cell disease goes undiagnosed?

Answer 33

20% children with undiagnosed SCD may die during first 2 years of life Acute infection Acute splenic sequestration Cerebrovascular accident – stroke

Question 34

what does screening for sickle cell disease provide?

Answer 34

Initiate prophylactic penicillin Parental education

Question 35

What can be screened by Tandem Mass Spectrometry?

Answer 35

Has the potential to detect up to ~ 50 IEM Amino acid disorders Fatty acid oxidation defects Organic acidaemias

Question 36

What is maple syrup Urine disease?

Answer 36

Maple Syrup Urine Disease; defect in branched chain 2-keto acid dehydrogenase complex