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)
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
