1. Genetic screening

2. 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

3. 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

4. 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)

5. % carriers Risk Black African 27 1 in 4 Chinese/SE Asian 8.5 1 in 12
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)
% carriers
Risk
Black African 27
1 in 4
Chinese/SE Asian
8.5
1 in 12
Indian/Pakistani 7
1 in 14
N European
0.2
1 in 500

6. 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

7. The future… Does it make a difference? Preconception screening?
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

8. Link to NHS Sickle Cell and Thalassaemia Screening programme leaflets

9. 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)

10. 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

11. 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)

12. 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

13. 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)

14. 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

15. 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%)

16. Hopefully…
Better understanding of genetic screening in antenatal and newborn period
Increased confidence when discussing with patients