Download Genetic screening

Genetic screening
Genetic screening
• Curriculum statement 6 Genetics in primary
care
– “Demonstrate an awareness of antenatal and
other screening programmes for genetic
conditions”
• Antenatal screening programme
• Newborn screening programme
• General screening
Antenatal/newborn screening
• NHS Sickle cell and Thalassaemia programme
– Pregnant women
– New born babies
• NHS newborn blood spot screening programme
–
–
–
–
–
Phenylketonuria (PKU)
Congenital hypothyroidism (CHT)
Sickle cell disease (SCD)
Cystic fibrosis (CF)
medium-chain acyl-CoA dehydrogenase deficiency
(MCADD)
• Foetal anomaly screening programme
– Includes screening for Down’s syndrome
NHS Sickle cell and Thalassaemia programme
• set up 2001
• first “linked” programme – i.e. mother’s
blood results linked to baby’s results
• covers both antenatal and new born
screening
• all pregnant women should be offered
testing, ideally before 10 weeks
• pregnant women from “high” prevalence
trusts should be automatically screened,
those from “low” prevalence trusts screened
using Family Origin Questionnaire (FOQ)
• Haemoglobinopathies most common within communities from
tropics/sub-tropics
• Currently 700,000 carriers (1.2% of the population) and 10% of the
ethnic population
• Sickle cell
– 240,000 carriers / 12,500 affected (currently)
– 2008/9: 670,00 newborn samples screened – 360 screen +ive with
disease (1/2000 births), 9600 identified as carriers
• Thalassaemia
– 214,000 carriers / 700 affected (currently)
Black African
Chinese/SE Asian
% carriers
27
8.5
Risk
1 in 4
1 in 12
Indian/Pakistani
N European
7
0.2
1 in 14
1 in 500
Family origin questionnaire
• For pregnant women living in an area with
“low risk” (foetal prevalence < 1.5/10,000
pregnancies) used to identify women at risk
of being a carrier or baby with
Haemoglobin disorder
• Ascertain family origins of mother and
father for at least 2 generations
• For women living in “high risk” areas helps
lab staff interpret results
The future…
• Does it make a difference?
– Not enough evidence from the UK
– USA: reduction in mortality in early infancy, earlier
interventions
• Preconception screening?
– Saudi Arabia: increase in number of at-risk couples
who cancel marriage proposals
– Lazio, Italy: universal screening secondary schools led
to reduction in affected births
• What do patients understand?
– Poor understanding of carrier status by patients
– Lack of understanding by professionals
Link to NHS Sickle Cell and
Thalassaemia Screening programme
leaflets
• http://sct.screening.nhs.uk/leaflets
NHS newborn blood spot screening
programme
• Established 1969 for PKU and 1981 for
CHT
• Screens 600,000 newborns every year
• > 99% babies screened, taken day 5-8
• Covers:
–
–
–
–
–
Phenylketonuria (PKU)
Congenital hypothyroidism (CHT)
Sickle cell disease (SCD)
Cystic fibrosis (CF)
medium-chain acyl-CoA dehydrogenase
deficiency (MCADD)
Phenylketonuria (PKU)
• Autosomal recessive condition
• Affects 1/10,000 births, 66 cases diagnosed each
year
• Twice as common in Ireland
• Abnormally high levels of Phenylalanine due to
reduction in phenylalanine hydroxylase
• “Classical” PKU = severe mental disability and
seizures if untreated
• “Benign” PKU = mild/moderate mental disability
if untreated
• Treatment = special diet
• Aim to diagnose and start treatment before 21
days of age
Cystic Fibrosis (CF)
• Introduced 1980 in England but not
universal until 2001
• Autosomal recessive
• Large number of gene mutations with range
of different clinical phenotypes
• Blood spot tests Immunoreactive
Trypsinogen (IRT)
• If raised, combination of DNA mutation
analysis and 2nd blood spot IRT performed
• Then confirmed with sweat test (if +ive or
equivocal)
Medium-chain acyl-CoA dehydrogenase
deficiency (MCADD)
• Testing started 2007, universal in England from
2009
• Autosomal recessive, deficiency of Medium chain
Acyl-CoA Dehydrogenase (needed to break down
medium chain fatty acids)
• Complications arise during times of “stress” i.e.
cannot break down fat stores so become
hypoglycaemic leading to seizures/brain
damage/death
• Generally no symptoms at birth, 1/3rd remain
asymptommatic
• Blood spot tests for raised Octanoylcarnitine
• Treatment = strict feeding regime
Down’s screening programme
• Trisomy 21 – 3 instead of 2 chromosomes
• Risk increases with maternal age (1/1500
aged 20 yrs, 1/900 aged 30 yrs and 1/100
aged 40 yrs)
• Offered to all pregnant women
• Generates a risk only (i.e. high or low risk)
• If high (more than or equal to 1/150)
diagnostic procedures offered
(Amniocentesis/Chorionic Villous
Sampling)
Down’s screening programme
• First trimester = Combined Screening test
– Offered from 10+0 to 14+1 weeks
– Bloods: bHCG and PAPP-A (Pregnancy
associated plasma protein A)
– USS:Foetal crown-rump length and Nuchal
translucency (significant if more than or equal
to 3.5mm)
– Above results + Maternal age used to calculate
risk
– Complies with standard of > 90% detection
rate and < 2% screen positive rate
Down’s screening programme
• Second trimester = Quadruple Screening
test
– Offered from 14+2 – 20+0
– Bloods: bHCG, aFP, Oestriol and Inhibin A
– Performance as a screening test less than that of
Combined (meets detection rate > 75% and
screen positive rate of < 3%)
Hopefully…
• Better understanding of genetic screening in
antenatal and newborn period
• Increased confidence when discussing with
patients