On Rare Disease Day, February 28th, many charities and companies will run events to raise awareness and generate change for the 300 million people worldwide living with a rare disease, their families and carers. Rare diseases will affect 1 in 17 of us in our lifetimes, but with over 7,000 rare diseases each affecting fewer than 1 in 2,000 people, experiences vary massively.

Individual experiences may be completely different even within the same disease with each case being unique to each person. This can make diagnosing rare diseases an incredibly complex and lengthy task. In fact, the “diagnostic odyssey” takes an average of 5.6 years, eight clinicians (including four specialists), and three misdiagnoses.

With 72% of rare diseases having a genetic cause, genomic sequencing has become an incredibly valuable tool in their diagnosis. In some cases, rapid sequencing has turned around a diagnosis in as little as 13 hours – as well as pointing to a treatment. This kind of speed is a rarity, but it highlights the incredible capabilities and applications of this type of technology.

Rapid sequencing

The tale of a baby receiving a diagnosis and treatment recommendations within the space of 13 hours has become a shining example of what’s possible, but there is a little more to the story. A CT scan first revealed signs of disease ​​in the 5-week-old’s brain, and then there was a clue pieced together by medical staff and the family: a decade earlier, the parents’ daughter had presented with similar symptoms at around the same age. This clue was what pointed staff towards the need to run gene panels, as well as which may be most appropriate to run. Without this initial human element and insight into the family’s medical history, the incredible turnaround may never have occurred.

Clinical decisions such as this require huge amounts of specialist experience. While technology cannot replace that experience (at least not yet), it can help. Clinical Decision Support modules – such as Cambio’s CDS – can help accelerate treatment timelines and support staff in making the best clinical decisions. Supporting clinicians to select and order the most appropriate gene panel as soon as possible is invaluable. In the case of that baby’s diagnosis, the time from the sequence starting to diagnosis was an incredibly short 13 hours, but the time from arrival in the emergency room to diagnosis was 36 hours. That gap between arrival and ordering the panel could have been reduced with tools such as CDS.

This example is of course on a massively accelerated and rare timeline compared to most people’s experiences of rare disease diagnosis, but it highlights that closing the gap between when patients initially present and ordering gene panels is the next key step in improving time to diagnosis.

The team involved in this case stressed that this incredible turnaround is not everyone’s experience – hospitals with fewer resources may not have access to the technology and, as this took place in the USA, insurance may get in the way. While the latter is not an issue here in the UK, health inequalities and differences in hospital resources remain.

Whole genome sequencing

Whole genome sequencing is now available through the NHS Genomic Medicine Service for certain conditions where the scientific evidence shows it can help improve patient care. Even though this test sequences the whole genome, it is usually looking for specific things relating to an already identified condition or possible conditions. This is because the genome contains such a vast amount of information that it would not be labour nor cost effective to examine the entire genome in depth. Even when the full genome is being sequenced, geneticists need to go in with a plan of action and know what they are looking for.

This is again where Cambio’s CDS solution comes in; CDS can direct clinicians towards which areas to focus on. While this is something that an experienced geneticist may be able to identify themselves, relying solely on personal expertise and experience is risky – if they focus in the wrong place, a key detail could be missed. Solutions such as CDS exist to augment the existing skillsets of clinicians rather than replace their expertise.

CDS is used as part of the GenOCEANIC solution that Cambio is rolling out in Northern Ireland in collaboration with the Belfast Health and Social Care Trust (BHSCT) team. GenOCEANIC (Genomics Open Core Engine Accelerating Northern Ireland Care) is based on an openEHR Clinical Data Repository to provide a platform for managing genomics activity. In brief, the platform combines the information held within genome sequences with patients’ electronic health records, building a full picture of their health to help reduce time to diagnosis and improve overall outcomes.

The results of a whole-genome sequence can help match patients to appropriate treatment pathways by identifying medications and interventions that will be the most effective as well as reducing the likelihood of an adverse drug reaction.

When people have their whole genome sequenced, they have the opportunity to contribute their genomic data (in an unidentifiable form) to a secure library hosted by Genomics England that can be accessed by approved researchers. Sharing this data massively amplifies the potential impacts of genomic sequencing; results will not only benefit the patient whose genome has been sequenced but anyone else who may share genetic similarities or the same diseases. These contributions have had – and will continue to have – a massive impact on the understanding and diagnosis of rare diseases across the country.