Prevalence distribution of rare diseases 200 180 160 140 120 100 80 Number of diseases 60 November 2009 40 May 2014 Number 1 20 0 0 5 10 15 20 25 30 35 40 45 50 Estimated prevalence (/100000) Prevalence of rare diseases: Bibliographic data Listed in alphabetical order of disease or group of diseases www.orpha.net Methodology A systematic survey of the literature is being Updated Data performed in order to provide an estimate of the New information from available data sources: EMA, prevalence of rare diseases in Europe. An updated new scientific publications, grey literature, expert report will be published regularly and will replace opinion. the previous version. This update contains new epidemiological data and modifications to existing data for which new information has been made Limitation of the study available. The exact prevalence rate of each rare disease is difficult to assess from the available data sources. Search strategy There is a low level of consistency between studies, a poor documentation of methods used, confusion The search strategy is carried out using several data between incidence and prevalence, and/or confusion sources: between incidence at birth and life-long incidence. - Websites: Orphanet, e-medicine, GeneClinics, EMA The validity of the published studies is taken for and OMIM ; granted and not assessed. It is likely that there - Registries, RARECARE is an overestimation for most diseases as the few - Medline is consulted using the search algorithm: published prevalence surveys are usually done in «Disease names» AND Epidemiology[MeSH:NoExp] regions of higher prevalence and are usually based OR Incidence[Title/abstract] OR Prevalence[Title/ on hospital data. Therefore, these estimates are an abstract] OR Epidemiology[Title/abstract] ; indication of the assumed prevalence but may not be accurate. - Medical books, grey literature and reports from experts are also important sources of data. Collected data Prevalence values provided are the mean of the highest and lowest values collected. When prevalence is not documented we calculate it using incidence: - For congenital diseases with birth-onset, prevalence = incidence at birth x (patient life expectancy/ general population life expectancy) ; - For the other rare diseases, prevalence = incidence x rare disease mean duration ; When no prevalence or incidence data are available, the number of cases or families reported in the literature is provided. The * sign indicates a life time prevalence. The ** sign indicates a birth prevalence. It was used when the birth prevalence was the only data available and a prevalence estimate was not possible because of a large variability in the duration of the disease. NB: Life expectancy of the French population (81 years) is used as the general population life expectancy. For any questions or comments, please contact us: [email protected] Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2014 - Number 1 2 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf Prevalence or reported number of published cases listed in alphabetical order of disease or group of diseases Number of Number of Estimated Estimated ORPHA published ORPHA published Disease or group of diseases prevalence Disease or group of diseases prevalence Number cases or Number cases or (/100,000) (/100,000) families families 94063 12q14 microdeletion syndrome 4 cases 926 Acatalasemia 3.2 199318 15q13.3 microdeletion syndrome 150 cases 48818 Aceruloplasminemia 0.1 94065 15q24 microdeletion syndrome 4 cases 929 Achalasia - microcephaly 5 cases 1606 1p36 deletion syndrome 15** 931 Acheiropodia < 10 families 268261 21q22.13q22.2 microdeletion syndrome 12 cases 932 Achondrogenesis 2.8** 567 22q11.2 deletion syndrome 5.6** 15 Achondroplasia 2.6** 79157 2-methylbutyryl-CoA dehydrogenase deficiency < 30 cases 49382 Achromatopsia 2.7 163693 2p21 microdeletion syndrome 7 cases 2561 Ackerman syndrome 8 cases 1617 2q24 microdeletion syndrome 23 cases 79086 Acquired generalized lipodystrophy > 100 251019 2q32q33 microdeletion syndrome < 25 cases cases 1001 2q37 microdeletion syndrome 10 cases 73274 Acquired hemophilia 0.1 7 3C syndrome 25 cases 2221 Acquired hypertrichosis lanuginosa 60 cases 35701 3-hydroxy-3-methylglutaryl-CoA synthase 9 cases 99147 Acquired Von Willebrand syndrome 300 cases deficiency 36 Acrocallosal syndrome 34 cases 2616 3M syndrome 40 cases 2008 Acro-cardio-facial syndrome 9 cases 67046 3-methylglutaconic aciduria type 1 20 cases 949 Acrocraniofacial dysostosis 2 cases 2975 46,XX disorder of sex development - skeletal 2 cases anomalies 37 Acrodermatitis enteropathica 0.2 2138 46,XX ovotesticular disorder of sex > 500 1786 Acrofacial dysostosis, Catania type 6 cases development cases 64542 Acrofacial dysostosis, Kennedy-Teebi type 2 cases 168558 46,XY disorder of sex development - adrenal 9 cases 1787 Acrofacial dysostosis, Palagonia type 4 cases insufficiency due to CYP11A1 deficiency 1788 Acrofacial dysostosis, Rodríguez type < 10 752 46,XY disorder of sex development due to 0.68 cases 17-beta-hydroxysteroid dehydrogenase 3 deficiency 1784 Acro-fronto-facio-nasal dysostosis 5 cases 168563 46,XY gonadal dysgenesis - motor and sensory 6 cases 965 Acromegaloid facial appearance syndrome < 20 cases neuropathy 963 Acromegaly 6 10 48,XXYY syndrome 1.9** 964 Acromegaly - cutis verticis gyrata - corneal 16 cases 22 4-hydroxybutyric aciduria 450 cases leukoma 33572 5-oxoprolinase deficiency 8 cases 39 Acromelanosis < 10 cases 75857 6q terminal deletion syndrome 19 cases 953 Acromesomelic dysplasia, Brahimi-Bacha type 3 cases 171829 6q16 deletion syndrome 7 cases 968 Acromesomelic dysplasia, Hunter-Thomson 10 cases type 178303 8q22.1 microdeletion syndrome 4 cases 40 Acromesomelic dysplasia, Maroteaux type 50 cases 915 Aarskog-Scott syndrome 0.4** 969 Acromicric dysplasia < 40 cases 916 Aase-Smith syndrome < 10 cases 955 Acroosteolysis dominant type 50 cases 920 Ablepharon macrostomia syndrome 15 cases 85203 Acro-pectoral syndrome 22 cases 921 Abruzzo-Erickson syndrome 4 cases 956 Acro-pectoro-renal dysplasia 12 cases 1658 Absence of fingerprints - congenital milia 14 cases 957 Acropectorovertebral dysplasia < 30 cases 2951 Absent thumb - short stature - 3 cases immunodeficiency 971 Acrorenal syndrome 20 cases 67043 Acanthamoeba keratitis 1 958 Acro-renal-mandibular syndrome 7 cases 90301 Acanthosis nigricans - Insulin resistance - 5 cases 959 Acro-renal-ocular syndrome < 20 muscle cramps - acral enlargement families * Lifetime prevalence ** Prevalence at birth Orphanet Report Series - Prevalence of rare diseases: Bibliographic data - May 2014 - Number 1 http://www.orpha.net/orphacom/cahiers/docs/GB/Prevalence_of_rare_diseases_by_alphabetical_list.pdf 3 Prevalence of rare diseases: Bibliographic data - Listed in alphabetical order of disease or group of diseases Number of Number of Estimated Estimated ORPHA published ORPHA published Disease or group of diseases prevalence Disease or group of diseases prevalence Number cases or Number cases or (/100,000) (/100,000) families families 163696 Action myoclonus - renal failure syndrome 17 cases 56 Alkaptonuria 0.5 69736 Acute bilateral depigmentation of the iris 5 cases 59 Allan-Herndon-Dudley syndrome 89 cases 98916 Acute inflammatory demyelinating 3.1 1005 Alopecia - contractures - dwarfism - 5 cases polyradiculoneuropathy intellectual disability 79276 Acute intermittent porphyria 0.54 1008 Alopecia - epilepsy - pyorrhea - intellectual 12 cases disability 79126 Acute interstitial pneumonia 3.8 700 Alopecia totalis 10.5 90062 Acute liver failure 23 701 Alopecia universalis 25 98918 Acute motor axonal neuropathy 0.1 726 Alpers syndrome 0.7** 98917 Acute motor-sensory axonal neuropathy 0.1 60 Alpha-1-antitrypsin deficiency 25 519 Acute myeloid leukemia 11* 61 Alpha-mannosidosis 0.2** 55881 Adamantinoma 0.11* 3137 Alpha-N-acetylgalactosaminidase deficiency < 20 2952 Adducted thumbs - arthrogryposis, Christian 3 families cases type 847 Alpha-thalassemia - X-linked intellectual > 200 45 Adenosine monophosphate deaminase > 100 disability syndrome cases deficiency cases 63 Alport syndrome 2 46 Adenylosuccinate lyase deficiency 50 cases 2131 Alternating hemiplegia of childhood 0.9** 1501 Adrenocortical carcinoma 1 284 Alveolar echinococcosis < 1000 2666 Adult familial nephronophthisis - spastic 2 cases cases quadriparesia 1021 Amaurosis - hypertrichosis 2 cases 178487 Adult intestinal botulism 19 cases 1946 Amelo-cerebro-hypohidrotic syndrome 39 cases 829 Adult Still's disease 1.25 171836 Amelogenesis imperfecta and gingival 4 cases 978 ADULT syndrome 14 cases hyperplasia syndrome 209335 Adult-onset proximal spinal muscular atrophy, 0.1 1908 Aminopterin/methotrexate embryofetopathy 17 cases autosomal dominant 1034 Amniotic bands 4** 83617 Agammaglobulinemia - microcephaly - 3 cases craniosynostosis - severe dermatitis 69 Amyloidosis 30 52055 Agenesis of the corpus callosum - intellectual 2 cases 803 Amyotrophic lateral sclerosis 5.2 disability - coloboma - micrognathia 228113 Anal fistula 23 98850 Aggressive systemic mastocytosis 0.2 98841 Anaplastic large cell lymphoma 2 990 Agnathia - holoprosencephaly - situs inversus 30 cases 142 Anaplastic thyroid carcinoma 0.1 50 Aicardi syndrome 1** 157954 ANE syndrome 5 cases 51 Aicardi-Goutières syndrome 120 cases 72 Angelman syndrome 1.1 52 Alagille syndrome 0.4** 63442 Angel-shaped phalango-epiphyseal dysplasia 15 cases 178333 Åland Islands eye disease > 5 2346 Angio-osteohypertrophic