Rare conditions included in Genomics England's world-leading study

This month, Genomics England published an initial list of more than 200 rare genetic conditions that will be investigated as part of our world-leading Generation Study (see BioNews 1210).

This NHS-embedded research study aims to sequence the whole genomes of 100,000 newborns to understand whether this can help identify rare, treatable genetic conditions earlier. The study also aims to facilitate wider research to learn more about genes and health, with the hope to improve testing and treatment for genetic conditions in the future. Evidence will be gathered throughout the study, in order to consider whether genome sequencing could be part of NHS newborn screening in the future.

The first 223 conditions that have been included on the list are caused by genetic changes in around 500 different genes. We first considered whether a condition met four key principles, developed after extensive consultation with NHS healthcare professionals, scientists, people living with rare conditions and the public:

• There is strong evidence that certain genetic variants within a gene cause a particular condition and can be reliably detected from genome sequencing. It is also important that we incorporate other non-genetic tests that can help to confirm the diagnosis of a condition – for example by looking for traces of certain chemicals in a baby's blood.

• A high proportion of the babies identified with those genetic variants would go on to develop that condition, which would have a debilitating impact on their quality of life. This should take into account the experience of patients and families who have these conditions, including self-reported scores where available, which can be used to calculate Quality Adjusted Life Years.

• An early or pre-symptomatic intervention would need to lead to substantially improved outcomes for the baby. This intervention should be initiated in early childhood, and could cure, delay or modify the course of the condition.

• The conditions to be screened should have an intervention that is accessible to all in the NHS. This is important in ensuring that no child or family is left to deal with the consequences of a rare condition on their own.

More information about these principles – and a helpful animated video – can be found on our website.

Determining whether a condition meets these principles can be challenging, because they are rare and our knowledge can be limited – but this is also where ongoing research can help. This is also the first time that genome sequencing is being investigated in a screening context in newborns on a nationwide scale. We therefore worked with NHS England to bring together a Clinical Assurance Group, to ensure there is a capacity in the NHS to provide the ongoing care and support that the child and family will need, as outlined in the final principle above. Through this group, we engaged with NHS clinicians and commissioners to review the evidence we provided for the conditions and genes in their specialty area.

Included in the initial list of conditions is severe combined immunodeficiency (SCID), which can be treated if diagnosed at an early stage. Approximately 14 babies are born a year with SCID and without treatment usually die before they are a year old. SCID results in immune system abnormalities that lead to a greater risk of infections and other life-threatening complications. If SCID is diagnosed early enough, babies can receive a bone marrow transplant that can help replace their faulty immune system with a healthy one.

Another condition on the initial list is biotinidase deficiency, which is an inherited condition where the body is unable to reuse and recycle the vitamin biotin, which is important for growth and development. Without treatment, children can have delayed development, seizures and problems with hearing and vision. If diagnosed early enough, biotinidase deficiency can be treated simply by providing a biotin supplement.

It is estimated that the Generation Study will identify suspected diagnoses for around 1000 of the 100,000 babies who take part. For each of those babies and their families, this information can be life-changing.

In the coming months, we will be continuing to work with NHS clinicians and scientists to ensure we only look for variants where we know, to the best of our knowledge, that they will cause one of these conditions. We'll also be working with those specialists to define the clinical pathways for each of these conditions, when a suspected diagnosis is found from the study.

Importantly, this initial list will be subject to further change during the course of the study, with conditions being added or removed in response to emerging research and evidence. Overall, we've taken a careful approach in deciding which condition to include, to make sure our processes work and that families receive safe and effective care. We'll revisit both the principles and the list of conditions while crucially continuing to engage with the public, specialists and the families with rare conditions.

If you have any questions for the Genomics England team, they can be contacted by emailing ge-servicedesk@genomicsengland.co.uk and quoting 'Generation Study' in the subject line.