Rare diseases in general practice: recognising the zebras among the horses

DIAGNOSING RARE DISEASES AND THE ROLE OF PRIMARY CARE

Patients frequently describe a long and protracted ‘diagnostic odyssey’, taking years, or even decades. These years can be defined by uncertainty, multiple hospital attendances, investigations, misdiagnoses, and inappropriate treatments; with huge emotional cost and wasted time, effort and resources ²

Even in the absence of a disease-specific therapy, a prompt and accurate diagnosis is of huge value. Early diagnosis can put an end to the exhausting diagnostic odyssey and diagnosis validates the individual’s symptomatology. It can help inform family planning, especially for inherited paediatric diseases where several children in a family may be affected before diagnosis, it informs prognosis and importantly, it assists the patient and family in gaining access to social and educational support.

So what role does general practice have in rare disease diagnosis? Where there is suspicion, an accurate three-generation family history may provide clues of an inherited disease. A review of the key features can form the basis of a problem-based search for differential diagnoses utilising web-based resources (for example, www.findzebra.com/; www.omim.org/; www.orpha.net/consor/cgi-bin/index.php; and phenomizer-orphanet: http://compbio.charite.de/phenomizer_orphanet/).^7,8,9

The differential diagnoses generated will then inform subsequent investigation and referral, advice is normally readily available from clinical genetic departments or, if an inborn error of metabolism is considered, regional specialist metabolic laboratories.

A GP CAN UNIQUELY HELP

Of course it is unrealistic to expect anyone to know all 7000 rare diseases, or for a GP to make an immediate spot diagnosis the moment a patient walks in. But GPs are in a unique position. We offer whole patient and family care with continuity of clinical record over many years. We are used to managing diagnostic uncertainty, excluding serious pathology and to consider diagnoses that we may only see a handful of times in our career, for example, infectious diseases such as meningococcal sepsis and certain cancers. By keeping an open mind we have the tools and ability to ‘join the dots’, identify unusual patterns of disease and revisit diagnoses.¹⁰ Asking: ‘ Is there a more plausible explanation for the patient’s problems? Or should we reinvestigate patients with newer advanced diagnostic tests?’

Patients with a rare disease typically seek an empowering and collaborative approach with their clinicians. They and their carers are often ‘expert patients’, which can challenge the traditional patient–doctor relationship, shifting the usual knowledge asymmetry. By acknowledging each other’s mutual skills and expertise an effective and rewarding partnership can be achieved.^9,11

THE FUTURE OF RARE DISEASES IN PRIMARY CARE

In 2013 the UK Strategy for Rare Disease highlighted the need for better coordination of care, the empowerment of patients, better diagnostics, and earlier disease interventions. It also highlighted the integral, yet difficult role that GPs have, especially in the diagnosis of rare diseases⁶ The UK Rare Disease Forum¹² has recently produced a report assessing the progress made toward the 51 published recommendations. The reports acknowledges the progress made in molecular diagnostics, including the 100 000 genome project, the expansion of the newborn screening programme in 2015 to include 4 more conditions (see Box 2) and a unified registry of rare disease patients, but highlights much work that still needs to be done to achieve the 2020 goal:¹³ ‘The UK Strategy for Rare Diseases sets out a shared vision for improving the lives of all those with rare diseases in the UK by 2020.’