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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