Consultations on screening for genetic disorders in the UK

16 February 2015

The UK National Screening Committee (NSC) is currently consulting on a number of screening issues.

In newborn screening, a consultation is open on rare inherited fatty acid oxidation disorders carnitine transporter deficiency (CTD) and very long chain acyl CoA dehydrogenase deficiency (VLCADD); and on rare inherited amino acid metabolism disorders argininosuccinic acidaemia, citrullinaemia and tyrosinaemia type I. None of these conditions is currently included in the recently expanded newborn screening panel in England.

The consultations, both of which close on 25th February, state that inclusion in newborn screening is still not recommended for any of these conditions. For the fatty acid oxidation disorders this is said to be because there is uncertainty over the accuracy of the screening test as most screening studies have not performed extensive follow-up, and therefore false-negatives could have been missed’. The clinical course of the condition is also variable and there is uncertainty over whether all cases identified via screening would require treatment.

For the amino acid metabolism disorders argininosuccinic acidaemia and citrullinaemia screening is not recommended because of uncertainties over the UK epidemiology, the timing of the test and the impact of treatment. However, screening for tyrosinaemia type I ‘could be considered’ subject to further evidence on the condition’s epidemiology, the feasibility of screening in the UK; and neurocognitive defects observed in some patients following treatment.

In antenatal (pregnancy) screening, a consultation is open on Fragile X Syndrome. The last review in 2011 concluded that Fragile X should not be screened for in pregnancy for two main reasons; the unsuitability of the test (unlike those for metabolic disorders, it is a DNA test, much less appropriate for large-scale delivery) and the inability to predict the clinical course of disease in permutation and full mutation carriers of either sex.

Fragile X Syndrome  is a complex X-linked condition; individuals with ‘full mutations’ (over 200 CGG repeats) in the Fragile X Mental Retardation 1(FMR1) gene have varying degrees of developmental problems, with males typically much more severely affected than females. Individuals with ‘pre-mutations’ of 55-200 CGG repeats have an increased risk of an adult-onset neurodegenerative disorder called fragile X tremor ataxia syndrome and for women, premature ovarian failure.

Prenatal testing is typically confined to women from families where Fragile X is known or suspected, although the complexities of the condition make counselling about the decision to test important. It has been suggested that antenatal screening of pregnant women for carrier status could be advisable since the population frequency is relatively high and the burden of the disease on families and health systems significant, but this view remains contentious.

The NSC consultation on Fragile X antenatal screening closes on 5th May.

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