The Challenge of Diagnosing Rare Diseases

Around 7% of the population will be affected by a rare disease, with 80% of these having a genetic origin. Despite advances in diagnostic technologies, rare diseases often still present a challenge to identify and treat appropriately.

We spoke to Dr Jayne Spink, Chair of Rare Disease UK and Chief Executive of Genetic Alliance UK, to learn more about the difficulties of diagnosing rare diseases, what this means for patients, and how this may improve in the future.

Anna MacDonald (AM): What makes diagnosing rare diseases particularly challenging?

Jayne Spink (JS): There are more than 6,000 rare diseases – some of them affect a very small number of individuals in the UK.  It is impossible for any single healthcare professional to be knowledgeable across the whole range of possible rare disease diagnoses.  In addition, rare diseases can be very complex with a range of possible manifestations and degrees of severity. Rare diseases can also look similar to more common conditions, or present in an unusual way, meaning that the underlying cause of the patient’s condition might be overlooked or mistaken. 

AM: How long do patients wait on average for a diagnosis, and what effects does late diagnosis have?

JS: The average rare disease patient consults with 5 doctors, receives 3 misdiagnoses and waits on average 4 years before receiving a correct diagnosis.  A long diagnostic odyssey can delay access to information and support.  It also slows down the process of being able to access the most appropriate and effective care and treatment.  Many rare diseases are progressive – so unnecessary delay in diagnosis can have a negative impact on the person’s health. At worst a misdiagnosis could lead to the patient receiving potentially harmful, inappropriate or ineffective treatment.

AM: How are developments in technologies such as next-generation sequencing impacting rare disease patients?

JS: The first human genome to be sequenced using conventional methods took just over a decade to appear in final draft.  Today it is possible to sequence an entire human genome in a day. In terms of sensitivity, newer sequencing techniques are also much more able to identify mosaicisms – mutations present in some but not all of the patient’s cells or tissues. The ability to link clinical and genetic data from a larger pool of patients, and to find the links between variation and disease more rapidly than was previously possible, is bringing benefits in terms of accuracy and speed of diagnosis.  This ability to more rapidly derive and interrogate genetic data is also delivering benefits in terms of developing and delivering targeting treatment and reducing the likelihood and impact of side effects.

AM: What hurdles need to be overcome to further improve the diagnostic process?

JS: In part, this is about ensuring that when healthcare professionals see patients with complex or unusual constellations of symptoms, they are primed to consider the possibility of rare disease and make the appropriate referrals. We’re not at the point where genome sequencing is routinely available to undiagnosed or difficult to diagnose patients whose condition is likely of genetic origin.  Great strides are being made in linking clinical and genetic data, a notable initiative in this respect is the 100,000 genomes project.  We are hopeful that these new technologies will underpin a fundamental transformation of the way diagnosis (and care and treatment decisions) are made.

Dr Jayne Spink was speaking to Anna MacDonald, Science Writer for Technology Networks.