Spotlight on rare diseases

Abstract

Feb 28 is Rare Disease Day, the theme of which this year is “bridging health and social care”. This 12th annual Rare Disease Day highlights the need for better coordination of medical, social, and support services to lessen the burden that rare diseases—often complex, chronic, and disabling—have on the everyday lives of patients, their families, and carers. As a recent Europe-wide survey found that 80% of patients and carers had difficulty completing daily tasks, 70% found organising care time-consuming (with 60% finding it hard to manage), and 67% felt that health, social, and local services communicated poorly with each other, the theme of Rare Disease Day 2019 is timely. More than 6000 rare diseases (80% with a genetic component) affect more than 300 million people worldwide. While an individual disease might be classed as rare (defined as affecting less than 1 in 2000 of the general population in the European Union or fewer than 200 000 people in the USA), the sheer number of rare diseases means that the overall numbers quickly stack up: 3·5 million people in the UK, 30 million across Europe, and 30 million in the USA are affected. Whether a single rare disease affects thousands or just one person, the impact on the affected individual and those around them can be devastating: 50% of rare diseases affect children, 30% of whom will die before age 5 years. Rare diseases present myriad challenges for patients, their families, and caregivers, including the time it takes to obtain a correct diagnosis for many patients. In a survey of patients and caregivers in the USA and UK, patients reported that it took on average 7·6 years in the USA and 5·6 years in the UK to get a proper diagnosis, during which time patients typically visited eight physicians (four primary care and four specialist) and received two to three misdiagnoses. As there is no approved treatment for 95% of rare diseases, a diagnosis can be a crushing reality check for patients and their families, rather than bringing hope and reassurance. As such, rare diseases impose a considerable emotional toll on patients and their caregivers. Other challenges include a lack of information and resources, the financial cost of care, and difficulty in accessing appropriate medical expertise, which is compounded by a lack of specialist training programmes for medical professionals. In this issue of The Lancet Diabetes & Endocrinology, we publish a call-to-action to address the unmet need for subspecialty training in adult rare (inherited metabolic) diseases, which is crucial given that 50% of rare diseases present in adulthood and children surviving rare diseases eventually transition to adult care. Despite formidable challenges in diagnosing, managing, and ultimately treating individuals with rare diseases, considerable progress is being made: pharmaceutical companies are increasingly interested in rare diseases (spurred by the incentives and tax breaks that orphan drug status affords), evidenced by the rising number of orphan designation requests and drugs granted market authorisation each year. While most progress has been made for cancer and haematological indications, many landmark advances have been made in the management and treatment of rare endocrine diseases. We have published three examples of such advances in recent weeks: 7-year outcomes for infants and young children, aged 3 years or younger at enrolment, with life-threatening hypophosphatasia treated with asfotase alfa; efficacy and safety of burosumab in children aged 1–4 years with X-linked hypophosphataemia; and overall survival and medullary thyroid carcinoma-specific survival in patients with multiple endocrine neoplasia type 2B. Feb 28 is a day to reflect on rare diseases: what has been achieved, and what needs to be done. While coordination between health and social care undoubtedly needs to be improved, radical new strategies to fund research and do clinical trials for rare diseases that affect only a handful of patients (too small a market to be commercially viable) need to be developed, repurposing of existing drugs for the treatment of rare diseases must be maximised, and the situation where drugs are developed but no one can afford them avoided. Above all else, we should recognise that, although these diseases might be individually rare, the challenges they pose for patients, families, and carers are common to millions of people worldwide.