Adrenoleukodystrophy is a rare genetic disorder caused by a mutation of the ABCD1 gene damaging the myelin sheath in the brain. The condition typically manifests during childhood with neurological symptoms such as attention deficit, hyperactivity and co-ordination problems, alongside auditory and visual impairments. Without treatment, adrenoleukodystrophy can result in severe disability or death. An X-linked inheritance pattern means males are often more severely affected due to their possessing only one X chromosome. However, an application to add screening for adrenoleukodystrophy to the UK’s male newborn screening programme was rejected by the UK’s National Screening Committee (NSC).
Adrenoleukodystrophy confers a high level of disease burden, so a screening programme aimed at male newborns in the UK could improve outcomes for many of those living with the disease and those caring for others with the disease. GlobalData’s epidemiological forecast estimates a total of more than 100 diagnosed prevalent cases of adrenoleukodystrophy in 2030, with a diagnosed prevalence of 0.0002%. A smaller prevalence of adrenoleukodystrophy is estimated in the US, where GlobalData forecasts more than 250 diagnosed prevalent cases of the disease in 2030, with a diagnosed prevalence of 0.0001%. In the US, 18 states routinely screen for the disease. As the diagnosed prevalence in the UK is estimated to be higher than that in the US, where screening programmes are widely used, this further supports the initiation of a screening programme within the UK.
However, adrenoleukodystrophy manifests in multiple different phenotypes. At present, existing stem cell transplant therapies only target one specific phenotype, namely childhood cerebral adrenoleukodystrophy. The NSC was unable to identify sufficient literature describing the proportion of those with mutations in the ABCD1 gene who go on to develop this treatable phenotype. Alongside limited data surrounding the specificity and sensitivity of currently available adrenoleukodystrophy screening tests, there is also a lack of data on the comparative effectiveness of treatment issued pre-symptomatically versus that issued to those already experiencing clinical symptoms.
Because of this, despite a higher prevalence of disease within the UK than in other countries that routinely screen for adrenoleukodystrophy, such as the US, the NSC concluded there was insufficient evidence to justify starting a newborn screening programme for adrenoleukodystrophy. Future proposals for starting a newborn screening programme in the UK would likely benefit from further studies into the remaining gaps in the literature surrounding the disease.