Lecture 32: Newborn screening Flashcards
What is screening?
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.
True or false: Screening is 100 % sensitive and specific
False
True or false: Screening is 100 % sensitive and specific
False
What are the 5 principles of the Wilson and Jungner criteria?
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
When are babies first tested after birth?
5 days (5-8 exceptional)
Summarise new-born screening in the UK:
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
What type of sample is taken at a screening early on?
Blood spot test
For positive babies, how quickly is it expected for babies to be on treatment with referral?
Within 3 days
What happens if a baby identified as missed?
A blank screening blood spot test is sent off
What does the new-born screening screen for?
-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)
What does the new-born screening screen for?
-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)
What is Phenylketonuria?
A genetic condition that causes increased levels of phenylalanine (an amino acid) in the body.
How rare is PKU?
Affects 1: 10,000 Caucasian births
How does it affect a baby if untreated?
Severe intellectual disability
(Excellent prognosis if treated from birth)
What is the screening test for PKU?
Screening test: bloodspot phenylalanine
Confirm diagnosis with plasma phenylalanine measurements
no need to measure enzyme or DNA
How does newborn screening in the UK differ from other countries?
Profile of diseases
Day of life of test
Not always provided by the state
5 things found in the history of untreated PKU?
Severe intellectual disability
seizures, tremors
spasticity
behavioural problems, irritability
eczema in childhood
5 things found in the history of untreated PKU?
Severe intellectual disability
seizures, tremors
spasticity
behavioural problems, irritability
eczema in childhood
How do you treat PKU?
- Low phenylalanine diet
(Requires careful monitoring
Risk tyrosine insufficiency
Risk vitamin and trace element deficiencies) - biopterin supplementation (sapropterin)
(Kuvan (recently approved by NICE for certain patients, starting imminently))
What is congenital Hypothyroidism?
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.
How many people does congenital Hypothyroidism affect?
Affects 1: 1,500 UK births
How is congenital hypothyroidism treated?
Treatment with thyroxine, carefully monitored
How is congenital Hypothyroidism screened for?
Screening test: bloodspot TSH
Confirm diagnosis with plasma thyroid function tests
What is MCADD?
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
What is screened for when investigating MCADD?
Screening test: bloodspot C8 and C8/C10 ratio
Confirmation of diagnosis:
Bloodspot acylcarnitines, urine organic acids, DNA analysis
What is the prognosis of MCADD if treated?
Prognosis: good if decompensation avoided. ‘Safe’ times between meals increases as children grow older
How is MCADD treated?
Avoidance of fasting
How many births does MCADD affect?
Affects 1:10,000 UK births
What is Cystic fibrosis?
A genetic disorder, in which the lungs and the digestive system get clogged with mucus.
How many births does CF affect?
Most common inherited, 1:2,500
Why was screening for CF initially controversial?
Not all cases detected by IRT-DNA protocol
Doubts about clinical benefits of early treatment
Identification of less severe variants
Identification of heterozygotes
What is the treatment for CF?
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
What is sickle cell disease?
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
What can be detected in relation to haemoglobinopathies in a screening?
detect carriers and compound heterozygotes with HbC/DPunjab/E/OArab/β-thal
β-thalassaemia major detected
How many births are affected by sickle disease?
Sickle disease affects 1:2000 babies (up to 1 in 300)
What happens if sickle cell disease goes undiagnosed?
20% children with undiagnosed SCD may die during first 2 years of life
Acute infection
Acute splenic sequestration
Cerebrovascular accident – stroke
what does screening for sickle cell disease provide?
Initiate prophylactic penicillin
Parental education
What can be screened by Tandem Mass Spectrometry?
Has the potential to detect up to ~ 50 IEM
Amino acid disorders
Fatty acid oxidation defects
Organic acidaemias
What is maple syrup Urine disease?
Maple Syrup Urine Disease; defect in branched chain 2-keto acid dehydrogenase complex
