Essay Focus www.thelancet.com Vol 371 June 14, 2008 2039 Why rare diseases are an important medical and social issue Arrigo Schieppati, Jan-Inge Henter, Erica Daina, Anita Aperia Rare diseases affect a limited number of individuals (defined as no more than one in 2000 individuals in the European Union and no more than about one in 1250 in the USA), 1 but the number of disorders that fit this definition is very large (>5000 according to WHO). Therefore, the number of patients affected by a rare disease could be about 30 million in Europe and 25 million in North America. 2–5 The true burden of rare diseases in Europe and elsewhere is difficult to estimate, since epidemiological data for most of these diseases are not available. Rare diseases are an important public-health issue and a challenge for the medical community. They are called health orphans, because rare diseases were neglected for many years. Similarly, before the USA passed the Orphan Drug Act in 1983, the pharmaceutical industry had neglected the development of treatments for rare diseases, hence the name orphan drugs. Public awareness about the difficulties of patients with rare diseases was first raised by the report of the National Commission on Orphan Disease of the US Government in 1989. 6 The Commission’s hearings with hundreds of stakeholders highlighted issues that affected patients’ care, such as little information on rare diseases, difficulties of financing research, drawbacks of providing adequate health insurance and coverage of medical expenses, and the limited availability of effective treatments. The International Classification of Diseases (ICD) that is used in most countries is not convenient for rare diseases. 7 The absence of a universally recognised coding system is an obstacle for reliable registration of patients in national or international databases, preventing assessment of the economic and social effects of rare diseases. For some disorders, national or international registries are available, which have been set up and maintained by researchers, patients’ associations, public institutions, or drug companies. The European Rare Disease Task Force of the Health and Consumers Protection Directorate General of the European Commission has set up a working group to collaborate with WHO on ICD-10, and is considering all other existing classifications to provide the rare-diseases community with a uniform system. Assessment of the prevalence of rare diseases was attempted by the European Organization for Rare Diseases (Eurordis), and Orphanet, with the support of the European Commission. 8 This study not only provided an estimate of the prevalence of several rare diseases (table), but also showed the absence of reliable data, low consistency between sources of information, and poor methodological quality of epidemiological studies. Additionally, facilities for biochemical or genetic testing are scarce. We use the collective term of rare diseases to include a very heterogeneous group of disorders that can affect any system. Most rare diseases are genetic disorders, which are often severely disabling, substantially affect life expectancy, and impair physical and mental abilities. These disabilities result in reduced quality of life, and affect an individual’s potential for education and earning capabilities. One example is inborn errors of metabolism, most of which are rare (prevalence between 1 in 1400 and 1 in 5000 livebirths). 9 An Italian prospective study (1985–97) on patients aged 0–17 years revealed that, of the 1935 newborn babies with inborn errors of metabolism identified by the study, only 11% reached adulthood. 10 Rare diseases also pose a considerable burden on the affected families. This burden was assessed by sending a questionnaire to 2500 patients with chronic diseases (8·2% of which were rare diseases). 1 Patients with rare disorders had the worst experience in terms of loss of social and economic opportunities, and of medical care. 1 Patients with rare diseases face diagnostic delays. This issue was shown in a survey of eight rare diseases (Crohn’s disease, cystic fibrosis, Duchenne muscular dystrophy, Ehlers-Danlos syndrome, Marfan’s syn- drome, Prader-Willi syndrome, tuberous sclerosis, and Lancet 2008; 371: 2039–41 See Editorial page 1972 See Comment page 1978 Clinical Research Centre for Rare Disease Aldo e Cele Daccò, Mario Negri Institute for Pharmacological Research, Bergamo, Italy (A Schieppati MD, E Daina MD; and Department of Woman and Child Health, Karolinska Institute, Astrid Lindgren Children’s Hospital, Stockholm, Sweden (Prof J-I Henter MD, Prof A Aperia MD) Correspondence to: Dr Arrigo Schieppati, Mario Negri Institute for Pharmacalogical Research, Via GB Camozzi, 3, 24020 Ranica, Bergamo, Italy raredis@marionegri.it For more on Eurordis see http://www.eurordis.org For more on Orphanet see http://www.orpha.net/ Estimated prevalence (per 100 000) Brugada syndrome 50 Erythropoietic protoporphyria 50 Guillain-Barré syndrome 47 Familial melanoma 46 Autism, genetic types 45 Tetralogy of Fallot 45 Scleroderma 42 Great vessels transposition 32·5 Focal dystonia 30 Marfan’s syndrome 30 Non-Hodgkin malignant lymphoma 30 Retinitis pigmentosa 27·5 Gelineau’s disease 26 Multiple myeloma 26 α1 antitrypsin deficiency 25 Congenital diaphragmatic hernia 25 Juvenile idiopathic arthritis 25 Neurofibromatosis type 1 25 Oesophageal atresia 25 Polycythaemia vera 25 Adapted from reference 8. Table: Rare diseases with the highest estimated prevalence