Programme of community action on rare diseasesec.europa.eu/health/ph_projects/2001/rare_diseases/fp_raredis_2001... · Programme of community action on rare diseases Contract 2001/CVG4

Programme of communityaction on rare diseases

Contract 2001/CVG4

ORPHANET :Final scientific report

February 2003

Final scientific report, february 2003 2/ 39

Summary

The project was to extend the content of the already existing ORPHANET database to buildup a truly European database. The first year (Dec 00-November 01) was the feasibility studyyear and a pilot study with four countries. The second year (Dec 01- Nov 02) was the year ofthe move from a French encyclopaedia to a European one, and the year of the collection ofdata on services in 7 countries.

For the encyclopaedia, a board of 83 editors has been established progressively, specialty byspecialty and authors of texts nominated. For the 3,500 diseases, there are on-line: 990summaries in French, 833 summaries in English, 445 review articles in French or in English.

The partners were trained to use our methodology through visits, e-mails and phone calls.Three meetings of all partners took already place: one in Paris on 5-6 February 2002, one inStrasburg on 30 May 2002, one in Rome on October 23,2002.

All the partners, including the new ones : Spain and Austria, have identified their sources ofinformation. The data about services are partially collected in all participating countries andalready released for Italy, Belgium, Switzerland, Germany and Spain. The amount of datareleased from countries other than France is: 236 patient support groups, 1946 diagnostictests, 103 research projects and 63 expert clinics.

All the thesaurus have been translated in Italian, German and Spanish as well as all thescreens of the web site. The number of names of diseases with their synonyms to betranslated was over 6,000.

The Italian, German and Spanish versions of the website are now active.

A quality charter has been defined by the partners and agreed on.

The usefulness of the database was assessed through the number of connections. In January2003, we have had during the month visits from 58,000 different sites from 105 differentcountries.

As a project leader of Orphanet, Ségolène Aymé was invited 19 times within the year of thecontract to give a lecture on Orphanet. These invitations came from the Academia, theIndustry and from Agencies and took place in five different European countries.

The Orphanet project is developing according to the plans. The first year was a very busy onewhich permitted to explore all the difficulties for transmitting our five-year experience withdata collection. The procedures are now well in place and should be easily adopted by thenew partners. The experience also clearly showed to the partners that there was a great needin getting national funding to expand the local teams. Several countries are on the way ofhaving complementary funding at the governmental level.


List of partnersSubject :ORPHANET

BELGIUM

Pr Jean-Pierre FrynsDirector of the Center for Human GeneticsUniversity of LeuvenCampus GasthuisbergHerestaat 49B-3000 LEUVENTel : 00 32 16 34 58 60Fax : 00 32 16 34 59 97

GERMANY

Pr Joerg SchmidtleDepartment of Human GeneticsCarl6Neuberg-Str. 1D-30625 HannoverTel : 00 49 511 532 6537Fax : 00 49 511 532 5865

ITALY

Pr Bruno DallapiccolaIstituto CSS – MendelViale Regina Margherita 26100196 ROMATel : 39 06 44 16 05 03Fax : 39 06 44 16 05 48

SWITZERLAND :

Dr Celia Delozier-BlanchetInstitute of Medical GeneticsCMU1, rue Michel – ServetCH-1211 GENEVE 4Tel : 00 41 22 702 57 07Fax : 00 41 22 702 57 06

AUSTRIA

Pr Gerd UtermannInstitut für Medizinische Biologie und HumangenetikDer Universität InnsbruckSchöpfstrasse 41A-6020 INSBRUCKTel : 00 43 512 50 73 450Fax : 00 43 512 50 72 861

SPAIN

Dr Miguel Del CampoUniversitat Pompeu FabraDepartment Cieucies ExperimentalsFacultat Ciencies de la SalutDr Aiguader 8008003 BARCELONA

PORTUGAL

Pr Margarida Reis LimaInstituto de Genetica MedicaPraça Pedro Nunes,88P-4050-466 PORTOTel : 00 351 22 607 03 07Fax : 00 351 22 607 03 99


Final scientific report 2002

Goal of the EC funded project

The project was to extend the content of the already existing ORPHANET database to buildup a truly European database. The first year (Dec 00-November 01) was the feasibility studyyear and a pilot study with four countries. The second year (Dec 01- Nov 02) was the year ofthe move from a French encyclopaedia to a European one, and the year of the collection ofdata on services in the 7 countries.

The European project has two parts:1- the establishment of an on-line Encyclopaedia on rare diseases2- the extension of the existing directory of services to services in 7 European countries.

1- The on-line Encyclopaedia

1.1 Editorial processThe Orphanet encyclopaedia is under the responsibility of an editorial board of 83 Europeanexperts. All the editing process takes place in Paris where 3 technical scientific editors areacting:

- They contact the editors to ask them to nominate authors- They approach the nominated authors- They check the quality of the manuscript and the conformity with the Orphanet

format- They send the manuscripts to editors for review- The do the final changes according to the editor’s requests- They inject the paper in the database

All the manuscripts are written in English. The summaries are translated into nationallanguages if resources are available (outside this contract). The translation into French issystematically done.

All the texts are updated once a year.

1.2 Editorial boardThe list of editors by specialty and by country is the following:

CARDIOLOGYPr Duboc, Paris, FranceDr Melacini, Padova, ItalyPr McKenna, London, UKPr Nigro, Napoli, Italy

DERMATOLOGYPr Blanchet-Bardon, Paris, FrancePr Caputo, Milan ItalyPr Eady, London, United Kingdom


Pr Happle, Marburg, GermanyPr Mascaro, Barcelona, SpainPr van Vloten, Utrecht, Netherlands

DYSMORPHOLOGYDr Cormier-Daire, Paris, FranceDr Devriendt, BelgiumPr Hennekam, Amsterdam, NetherlandsPr Lacombe, Bordeaux, FrancePr Verloes, Liège, Belgium

EMBRYOFEOTOPATHYDr Gonzalez, Paris, FranceDr Robert-Gnansia, Lyon, FranceDr Subtil, Lille, France

ENDOCRINOLOGYPr Bouchard, France

GASTROENTEROLOGYPr Chayvialle, Lyon, FrancePr Rösch, Frankfurt/Main, Germany

HEMATOLOGIEPr Glückman, Paris, France

HEPATOLOGYPr Valla, Clichy, FrancePr Reichen, Bern, Germany

IMMUNOLOGYPr Fischer, Paris ,FrancePr Notarangelo, Brescia, Italy

INFECTIOUS DISEASESPr Caramello, Turin, ItalyPr Carbon, Paris, FrancePr Danis, Paris, FrancePr Feldmeier, Berlin, GermanyPr Hommel, Liverpool, UKPr Lew, Geneva, SwitzerlandPr Lode, Berlin, Germany ;Pr van der Meer, Nijmegen, Netherlands

INTERNAL MEDECINE/RHEUMATOLOGYDr Font, Barcelona, SpainPr Guillevin, Paris, France ;Pr Mariette, Paris, FranceDr Moutsopoulos, Athena, GreecePr Rizzoli, Geneva, Switzerland

METABOLIC DISEASESPr Bachman, Lausanne, SwitzerlandPr Baumann, Paris, FrancePr Federico, Sienna, ItalyPr Leonard, London, United KingdomPr Saudubray, Paris, FrancePr van den Berghe, Bruxelles, Belgium


Pr Wendel, Dusseldorf, Germany

NEPHROLOGYPr Grunfeld , Paris , FrancePr Haycock , London, United KingdomPr Niaudet, Paris, FrancePr Scolari, Brescia, ItalyPr Sessa, Vimercate, Italy

NEUROLOGYPr Brice, Paris, FranceDr Gasser, Munich, GermanyDr Taroni, Milan, ItalyPr de Visser, Amsterdam, NetherlandsPr Palau, SpainPr Filla, Italy

NEUROMUSCULAR DISORDERSDr Bonnemann, Göttigen, GermanyPr Merlini, Bologna, ItalyPr Muntoni, London, United KingdomDr Padberg, Nijmegen, the NetherlandsDr Urtizberea, Paris, France

NEUROPEDIATRIC DISEASESPr Campos-Castello, Barcelone, SpainPr Motte, Reims, FrancePr Ponsot, Paris, France

ONCOLOGYPr Fernandez-Delgado, Valencia, SpainPr Philip, Lyon, FrancePr Pinkerton, Sutton, United KingdomPr Vassal, Villejuif, France

OPHTALMOLOGYDr Dufier, Paris, FrancePr Gaudric, Paris, FrancePr de Laey, Gent, BelgiumPr Marshall, London, UKPr Marsili, Milano, ItalyPr Mayer, Erlangen, Germany

OTOLARYNGOLOGYPr Anniko, SwedenPr Martini, Ferrara, ItalyPr Sterkers, Paris, FrancePr van de Heyning, Antwerp, Belgium

PRIONS DISEASESPr Alpérovitch, France

PNEUMOLOGYPr du Bois, London, United KingdomPr Cordier, Lyon, FrancePr Costabel , Essen, GermanyDr Lazor, Geneva, Switzerland


PEDIATRIC CARDIOLOGYPr Anderson, London, United KingdomDr Bonnet, Paris, FranceDr Marino, Roma, ItalyDr Parsons, Leeds, United KingdomDr Seghaye, Munich, Germany

PEDIATRICS RHEUMATOLOGYPr Dressler, Hannover, Germany.Dr Prieur, Paris, France

PEDIATRIC SURGERYPr Bargy, Paris, France

TOXICOLOGYPr Baud, Paris, France

These editors nominate potential authors who are asked to provide a review article in English.

1.3 Contributing authorsThe list of authors who have already written up one or more entries, or accepted to do so isthe following:

EUROPEAN TEXTS ON LINE OR PENDING - February 2003Disease name Author Status

2,8 dihydroxyadenine urolithiasis SIMMONDS Online

3C syndrome FAIVRE Online

4-hydroxybutyricaciduria JAEKEN Online

5-oxoprolinase deficiency RISTOFF Online

6-pyruvoyl-tetrahydropterin synthase, deficiency DHONDT Online

Aarskog syndrome PHADKE Online

Aase syndrome ALBUISSON pending

Abnormal systemic veinous return ANDERSON Pending

Achondrogenesis FAIVRE Online

Achromatopsia incomplete, X-linked ROCHE Online

Acrocephalopolydactyly NAEYAERT Online

Acromegaloid facial appearance syndrome ALBUISSON pending

Acromesomelic dysplasia Hunter-Thompson type FAIVRE Online

Acromesomelic dysplasia, Grebe type FAIVRE Online

Acromesomelic dysplasia, Maroteaux type FAIVRE Online

Acute articular rheumatism WEIL pending

Acute eosinophilic pneumonia, idiopathic PHILIT Online

Acute lymphoblastic leukemia VASSAL Online

Adenosine monophosphate deaminase deficiency GROSS Online

Adenylosuccinate lyase deficiency SAUDUBRAY Online

Adrenoleukodystrophy, X-linked AUBOURG Online

Adult Onset Still's disease FAUTREL Online

Agammaglobulinemia X-linked FISCHER Online


Agammaglobulinemia, autosomal recessive DURANDY Online

Aganthia holoprosencephaly situs inversus DELAHAYE pending

Aglossia adactylia ROBERT-GNANSIA Online

Aicardi-Goutieres syndrome LEBON Online

Albinism ocular ROCHE Online

Albright hereditary osteodystrophy KOTTLER Online

Aldolase A deficiency BAUSSAN Online

Alexander disease RODRIGUEZ Online

Allan-Herndon syndrome SCHWARTZ Online

Alpha thalassemia-mental retardation, X linked GIBBONS Online

Alpha-mannosidosis MAIRE Online

Alport syndrome SESSA Online

Alzheimer disease, familial BRICE Online

Amaurosis congenita of Leber ROCHE Online

Amelogenesis imperfecta x linked CRAWFORD pending

Aminopterin embryofetopathy ROBERT-GNANSIA Online

Amyloidosis GRATEAU Online

Amyotrophic lateral sclerosis VAN DER GRAAFF Online

Anaplastic large cell lymphoma VASSAL Online

Anderson disease BOLDRINI Online

Aneurysm of sinus of Valsalva KAEMMERER Pending

Angioneurotic edema BOUILLET Online

Ankylosing spondylarthritis DOUGADOS Online

Anophthalmos, clinical ROCHE Online

Anorexia nervosa, genetic types GORWOOD Online

Antiphospholipid syndrome TEKTONIDOU Online

Antisynthetase syndrome TZIOUFAS Online

Aortic arch interruption PONGIGLIONE Pending

Aortic arches defect GOLDMUNTZ Pending

Aorto-ventricular tunnel MACKAY Pending

Argininosuccinicaciduria SAUDUBRAY Online

Arrythmogenic right ventricular dysplasia THIENE On line

Aspartylglycosaminuria MAIRE Online

Asperger syndrome ATTWOOD Online

Ataxia, Friedreich-like, with selective vitamin E deficiency BRICE Online

Atrial septal defect atrioventricular conduction BENSON Online

Atrial septal defect atrioventricular conduction BENSON Online

Atypical coarctation of aorta KAEMMERER Online

Autoimmune lymphoproliferative syndrome LE DEIST Online

Autosomal recessive cerebellar ataxia PALAU Pending

Bardet-Biedl syndrome BONNEAU Online

Barth syndrome DE LONLAY Online

Bartsocas papas syndrome ROBERT-GNANSIA Online


Bartter syndrome COLUSSI Online

Beckwith-Wiedemann syndrome GICQUEL Online

Behcet disease WECHSLER Online

Behr syndrome ORSSAUD Online

Benign epilepsy of childhood with rolandic spikes (BECRS) PRATS-VINAS Online

Benign familial infantile epilepsy PLOUIN Online

Berger disease SAVOLDI Online

Best disease ZRENNER Online

Betaketothiolase deficiency FUKAO Online

Beta-mannosidosis LEVADE Online

Bethlem myopathy URTIZBEREA Online

Blount disease DELAHAYE pending

Boomerang dysplasia DELAHAYE pending

Brain stem tumor GRILL Online

Brittle bone syndrome lethal type ROBERT-GNANSIA Online

Bronchiolitis obliterans with obstructive pulmonary disease CORDIER Online

Brugada syndrome NAPOLITANO Online

Buerger's disease ARKKILA Online

Bullous pemphigoid BERNARD Online

Burkitt lymphoma VASSAL Online

CACH syndrome RODRIGUEZ Online

Caffey disease HALL Online

Camurati engelmann disease ALBUISSON Pending

Cardiac conduction defect, familial POLITANO Pending

Cardiac diverticulum VAZQUEZ-JIMENEZ Online

Cardiomyopathy dilated with conduction defect COMI Online

Cardiomyopathy hearing loss type trna lys gene mutation DE LONLAY Pending

Cardiomyopathy, familial dilated MESTRONI Pending

Carnitine palmitoyl transferase 2 deficiency BONNEFONT Online

Carnitine uptake deficiency SAUDUBRAY Online

Carnitine-acylcarnitine translocase deficiency BRIVET Online

Carnosinemia JAEKEN Online

Castleman disease SARROT-REYNAULD Online

Cataract, total congenital ROCHE Online

Cataract-microcornea syndrome GRONEMEYER Online

CDG syndrome SETA Online

Celiac disease HOLTMEIER OnlineCerebellar ataxia areflexia pes cavus optic atrophy andsensorineural hearing loss

ROBERT-GNANSIA Online

Cerebelloparenchymal disorder 3 MÉGARBANE Online

Cerebral arterio-venous fistula LASJAUNIAS Pending

Chaotic atrial tachycardia VILLAIN Pending

CHARGE association BLAKE Pending


Chorioretinopathy, birdshot type PRIEM Online

Choroideremia HOYNG Online

Chronic berylliosis MÜLLER-QUERNHEIM Online

Chronic hiccup CABANE Online

Churg-Strauss syndrome GROSS Online

Cluster headache VISY Online

Coats disease DEL LONGO Online

Coffin-Lowry syndrome HANAUER Online

Cofs syndrome ALBUISSON Pending

Cogan syndrome VINCENEUX Online

Cohen syndrome Kivitie-Kallio Pending

Colon cancer, familial nonpolyposis OLSCHWANG Online

Complete atrioventricular canal CALABRÒ Online

Congenital mitral malformation BONNET Pending

Congenital nephrotic syndrome, finnish type NIAUDET Online

Congenital rubella syndrome ROBERT-GNANSIA Online

Connexin 26 anomaly MARLIN Online

Conotruncal cardiopathy, familial WILSON Pending

Conotruncal heart malformations QUERO Pending

Continuous spike-wave during slow sleep syndrome METZ-LUTZ Online

Coronaro-cardiac fistula QURESHI Pending

Coronary arteries congenital malformation BONNET Pending

Corpus callosum agenesis MOUTARD Online

Crigler-Najjar syndrome LABRUNE Online

Criss-cross heart SANDERS Online

Crohn disease CORTOT Online

Cryoglobulinemia FERRI Online

Cryptogenic organized pneumopathy CORDIER Online

Cutis verticis gyrata REYGAGNE Online

Cystinosis NIAUDET Online

Dandy walker facial hemangioma NAULAERS Pending

De sanctis cacchione syndrome ALBUISSON Pending

Defective expression of HLA class 2 FISCHER Online

Dehydratase deficiency DHONDT Online

Deletion 1p36 SLAVOTINEK Pending

Deletion 2q24 MAAS Online

Deletion 4p WIECZOREK Pending

Deletion 5q35 STOLL Online

Dent disease GRUNFELD Online

Dentatorubral pallidoluysian atrophy BRICE Online

Denys-Drash syndrome NIAUDET Online

Dermatomyositis CHERIN Pending

DES embryofetopathy ROBERT-GNANSIA Online


Desbuquois syndrome FAIVRE Online

Dextrocardia ANDERSON Pending

Diabetic embryopathy ROBERT-GNANSIA Online

Diffuse leiomyomatosis with Alport syndrome SESSA Online

Dihydropteridine reductase deficiency DHONDT Online

Distal myopathy with vocal cord weakness PENISSON-BESNIER Online

Distal myopathy, Nonaka type PENISSON-BESNIER Online

Dopamine beta-hydroxylase deficiency SENART Online

Double discordia ANDERSON Pending

Double outlet right ventricle WILKINSON Online

Double outlet right ventricle WILKINSON On line

Duane syndrome PIOZZI Online

Dubowitz syndrome TSUKAHARA Online

Eales disease BARTOLUCCI Online

Ebstein anomaly WILKINSON Pending

Ectopic coarctation KAEMMERER Online

Elejalde syndrome NAEYAERT Online

Eosinophilic idiopathic chronic pneumopathy MARCHAND Online

Ependymoma VASSAL OnlineEpidermolysa bullosa simplex and limb girdle musculardystrophy

URTIZBEREA Online

Erythroderma lethal congenital ROBERT-GNANSIA Online

Ewing sarcoma VASSAL Online

Exostoses, multiple LEGEAI-MALLET Online

Faciocardiomelic dysplasia lethal ROBERT-GNANSIA Online

Familial adenomatous polyposis OLSCHWANG Online

Familial amniotic bands ROBERT-GNANSIA Online

Familial focal segmental glomerulosclerosis GRUNFELD Online

Familial hemophagocytic lymphohistiocytosis (FHL) DE SAINT-BASILE Online

Fanconi anemia MOUSTACCHI Online

Farber lipogranulomatosis LEVADE Online

Fetal dihydantoin syndrome ROBERT-GNANSIA Online

Fetal iodine syndrome ROBERT-GNANSIA Online

Fetal methyl mercury syndrome ROBERT-GNANSIA Online

Fetal minoxidil syndrome ROBERT-GNANSIA Online

Fetal trimethadione syndrome ROBERT-GNANSIA Online

Fetal valproic syndrome ROBERT-GNANSIA Online

FG syndrome OPITZ Online

Fibrochondrogenesis AL-GAZALI Online

Fibrodysplasia ossificans progressiva URTIZBEREA Online

Fibromatosis juvenile hyaline RAHMAN Online

Fixed subaortic stenosis HAUSER Online

Fraser syndrome ROBERT-GNANSIA Online


Friedreich ataxia BRICE Online

Frontonasal dysplasia klippel feil syndrome DELAHAYE Pending

Fructose-1,6-bisphosphatase deficiency BAUSSAN Online

Fumaric aciduria SAUDUBRAY Online

Galactosialidosis MAIRE Online

Gamma-glutamyl transpeptidase deficiency RISTOFF Online

Gamma-glutamylcysteine synthetase deficiency RISTOFF Online

Gaucher disease STIRNEMMAN Pending

Generalized epilepsy with febrile seizures plus (GEFS+) GOURFINKEL-AN Online

Giant cell arteritis DUHAUT Online

Gitelman syndrome MEIJ Online

Glaucoma, hereditary DUREAU Online

Glucosephosphate isomerase deficiency MAX-AUDIT Online

Glutaryl-CoA dehydrogenase deficiency HOFFMANN Online

Glycogen storage disease type 1 MAIRE Online


Glycogen storage disease type 2B FROISSART Online



Glycogen storage disease type 5 MAIRE OnlineGlycogen storage disease type 6A, due to phosphorylase kinasedeficiency

MAIRE Online

Glycogen storage disease type 6B, due to liver phosphorylasedeficiency

MAIRE Online


Glycogenose, type 0 MAIRE Online

Goodpasture pneumorenal syndrome ROSSERT Online

Gorlin syndrome LO MUZIO Online

Great vessels transposition COOK Pending

Griscelli disease DE SAINT-BASILE Online

GTP cyclohydrolase deficiency DHONDT Online

Guanidinoacetate methyltransferase deficiency STOECKLER-IPSIROGLUOnline

Gusher syndrome MARLIN Online

Hallervorden-Spatz disease HARPEY Online

Heart tumor of child UZUN Pending

Hemangiopericytoma MAREC-BÉRARD Online

Hemochromatosis familial BRISSOT Online

Hepatoblastoma VASSAL Online

Hereditary methemoglobinemia, recessive BEAUVAIS Online

Hereditary primary hypomagnesemia (generic term) MEIJ Online

Hirschsprung disease deafness polydactyly ALBUISSON Pending

Hirschsprung disease type d brachydactyly MOWAT Pending

His bundle tachycardia VILLAIN Online

His bundle tachycardia VILLAIN Online


Histidinemia LEVY Online

Hodgkin disease VASSAL Online

Holt-Oram syndrome BOSSERT Pending

Homocarnosinosis JAEKEN Online

Homocystinuria due to cystathionine beta-synthase deficiency YAP Pending

Huntington disease BRICE Online

Hyperferritinemia, hereditary, with congenital cataracts BEAUMONT Online

Hyper-IGM syndrome, autosomal recessive DURANDY Online

Hyper-IGM syndrome, X-linked FISCHER Online

Hyperimmunoglobinemia D with recurrent fever GRATEAU Online

Hyperornithinemia SAUDUBRAY Online

Hyperoxaluria NIAUDET OnlineHypomagnesemia caused by selective magnesiummalabsorption

MEIJ Online

Hypomagnesemia with hypocalciuria MEIJ Online

Hypomagnesemia with normocalciuria MEIJ Online

Hypoparathyroidism, deafness and renal disease (HDR) GRUNFELD Online

Hypoplastic left heart syndrome WILSON Pending

Idiopathic neonatal atrial flutter WREN Pending

IgA, selective deficiency of FISCHER Online

Immune deficiency, familial variable FISCHER OnlineImmune dysregulation, polyendocrinopathy, enteropathy, X-linked

CASANOVA Online

Incessant infant ventricular tachycardia WEREN Pending

Inclusion body myositis, IBM CHERIN Pending

Indomethacin embryofetopathy ROBERT-GNANSIA Online

Infantile recurrent chronic multifocal osteomyelitis GIRSCHICK Online

Interferon gamma, receptor 1, deficiency FISCHER Online

Iridogoniodysgenesis, dominant type DUREAU Online

Isthmian coarctation KAEMMERER Pending

Johanson-Blizzard syndrome STEINBACH Online

Kallmann syndrome HARDELIN Online

Kawasaki disease MAHR Online

Kimura disease LARROCHE Online

Klinefelter syndrome GRAHAM Online

Langerhans cell histiocytosis DONADIEU Online

Left ventricle-aorta tunnel BONNET Pending

Lesch-Nyhan syndrome TORRES JIMÉNEZ Online

Li-Fraumeni syndrome CHOMPRET Online

Linitis plastica POCARD Online

Lipodystrophy, Berardinelli type VAN MALDERGEM Online

Lissencephaly syndrome type 1 PILZ Pending

Long QT syndrome BEHR Pending

Lymphangioleiomyomatosis JOHNSON Online


Lymphoblastic lymphoma VASSAL Online

Macrophagic myofasciitis CHERIN Online

Macular degeneration, age-related MARDIN Online

Malignant hyperthermia susceptibility NIVOCHE Online

Marfan syndrome LEPARC Online

Maternal hyperphenylalaninemia ABADIE Online

Mediterranean fever, familial TOUITOU Online

Medullary cystic kydney disease, autosomal dominant AMOROSO Online

Medulloblastoma VASSAL Online

Megalencephalic leukodystrophy LOPEZ-TERRADAS Online

Mendelian susceptibility to atypical mycobacteria CASANOVA Online

Menkes syndrome CORDIER-ALEX Online

Mental retardation, X linked, marfanoid habitus VAN BUGGENHOUT Online

Mesangial sclerosis, diffuse NIAUDET Online

Methimazole embryofetopathy ROBERT-GNANSIA Online

Methylmalonicaciduria with homocystinuria SAUDUBRAY Online

Microcoria, congenital ROCHE Online

Microdeletion 22q11 PHELANT Pending

Microphthalmia, Lentz type ROCHE Online

Microscopic polyangiitis JENNETTE Online

Mitral atresia BONNET Pending

Molybdenum cofactor deficiency SAUDUBRAY Online

Muckle-Wells syndrome GRATEAU Online

Mucopolysaccharidosis type 1 BECK Online

Mucopolysaccharidosis type 2 MAIRE Online

Mucopolysaccharidosis type 6 FROISSART Online

Mucopolysaccharidosis type 7 MAIRE Online

Mucosulfatidosis MAIRE Online

Multiple sclerosis CHABAS Online

MURCS association CARRANZA-LIRA Online

Muscular dystrophy limb-girdle (generic term) VAN DER KOOI Online

Muscular phosphorylase kinase deficiency BAUSSAN Online

Myoclonic dystonia GASSER Online

Myoneurogastrointestinal encephalopathy syndrome LOMBES Online

N5-methylhomocysteine transferase deficiency SAUDUBRAY Online

Nail-patella syndrome NIAUDET Online

Nance-Horan syndrome TOUTAIN Online

Nasopharyngeal cancer BRENNAN Online

Naxos disease PROTONOTARIOS Online

Nephroblastoma VASSAL Online

Nephronophtisis NIAUDET Online

Nephropathy familial with gout GHIGGERI Online

Nephrotic syndrome, idiopathic steroid-resistant NIAUDET Online


Neuroblastoma VASSAL Online

Neurofibromatosis type 2 OLSCHWANG Online

Neurofibromatosis type 6 PINSON Online

Neuropathy hereditary motor and sensory lom type KALAYDJIEVA Online

Neuropathy hereditary with liability to pressure palsies GILBERT Online

Night blindness, congenital stationary ROCHE Online

Non-alcoholic steatohepatitis DUFOUR Online

Non-Hodgkin malignant lymphoma (generic term) VASSAL Online

Norrie disease ROCHE Online

Oculopharyngeal muscular dystrophy URTIZBEREA Online

Oligomeganephronic renal hypoplasia NIAUDET Online

Olivopontocerebellar hypoplasia lethal type ROBERT-GNANSIA Online

Ophthalmo acromelic syndrome TEKIN Online

Optic atrophy ORSSAUD Online

Optic atrophy, Leber type ORSSAUD Online

Optic nerve coloboma with renal disease GRUNFELD Online

Ornithine carbamoyltransferase deficiency SAUDUBRAY Online

Orofaciodigital syndrome type1 PRATI Online

Osteogenesis imperfecta CHEVREL Online

Osteopetrosis, malignant WILSON Pending

Osteosarcoma VASSAL Online

Ovarian germ cell malignant tumor RAY-COQUARD Online

Ovarian tumor of sex cord-stromal origin RAY-COQUARD Online

Oxoglutaricaciduria SAUDUBRAY Online

Pallister-Hall syndrome LACOMBE Online

Parkinson disease, genetic types BRICE Online

Parsonage-Turner syndrome KOLEV Online

Partial atrioventricular canal BINI Online

Patent ductus arteriosus familial MARTIN Pending

Pendred syndrome MARLIN Online

Pericardium congenital anomaly GILDEIN Online

Persistent hyperinsulinemic hypoglycemia of infancy DE LONLAY Online

Peters anomaly ROCHE Online

Peters-plus syndrome ROCHE Online

Peutz-Jeghers syndrome OLSCHWANG Online

Phenobarbital embryopathy ROBERT-GNANSIA Online

Pheochromocytoma PLOUIN Online

Phosphoglycerate kinase 1 deficiency MAX-AUDIT Online

Phosphoribosylpyrophosphate synthetase superactivity BECKER Online

Pigmentary retinopathy DOLLFUS Online

Pipecolic acidemia SAUDUBRAY Online

Plasminogen activitor inhibitor type 1 deficiency, congenital ANGLES-CANO Online

Platelet ADP P2Y12 receptor targeted by anti-thrombotic NURDEN Online


drugs, deficiency of

Polycystic kidney disease, dominant type NIAUDET Online

Polycystic kidney disease, recessive type NIAUDET Online

Polymicrogyria VILLARD Online

Polymorphic catecholergic ventricular tachycardia LUCET Online

Polymorphic catecholergic ventricular tachycardia LUCET On line

Polymyositis CHERIN Pending

Post-poliomyelitic syndrome NOLLET Online

Primary ciliary dyskinesia ETIENNE Online

Primary lateral sclerosis BRUGMAN Online

Primary pulmonary lymphoma CADRANEL Online

Progeria FAIVRE Online

Progressive external ophtalmoplegia LOMBES Online

Prolidase deficiency JAEKEN Online

Pseudohypoaldosteronism type 1 GRUNFELD Online

Pseudomyxoma peritonei SHERER Online

Psoriatic arthritis COMBE Online

Pulmonar fibrosis, idiopathic CORDIER Online

Pulmonary alveolar proteinosis, congenital RUSSI Online

Pulmonary arterio-veinous fistula CORDIER Online

Pulmonary artery coming from the aorta AZCARATE Pending

Pulmonary branches stenosis BOUDJEMLINE Pending

Pulmonary Langerhans' cell histiocytosis in adult TAZI Online

Pulmonary supravalvular stenosis BOUDJEMLINE Pending

Pulmonary valve stenosis BOUDJEMLINE Pending

Pulmonary valves agenesis SAUER Pending

Pulmonary veins stenosis HOVELS-GURISH Pending

Pulmonary venous return anomaly HOVELS-GURISH Pending

Pyomyositis LORTHOLARY Online

Pyroglutamicaciduria RISTOFF Online

Pyruvate kinase deficiency MAX-AUDIT Online

Relapsing polychondritis DROSOS Online

Renal hypomagnesemia, hypercalciuria, nephrocalcinosis KNOERS Online

Retinoblastoma VASSAL Online

Retinoschisis, X-linked ROCHE Online

Rett syndrome MANCINI Online

Rhabdomyosarcoma VASSAL Online

Right atrium familial dilatation BONNET Pending

Right ventricule hypoplasia BONNET Pending

Robinow syndrome DELAHAYE Pending

Saethre-Chotzen syndrome CLAUSER Online

SAPHO syndrome SCHILLING Online

Sarcosinemia JAEKEN Online


Schindler disease MAIRE Online

Schnitzler syndrome LIPSKER Online

Scleroderma VLACHOYIANNOPOULOSOnline

Scott syndrome KERBIRIOU-NABIAS Online

Seckel syndrome FAIVRE OnlineSevere combined immunodeficiency due to adenosinedeaminase deficiency

PERIGNON Online

Severe combined immunodeficiency, T- B+ due to JAK3deficiency

NOTARANGELO Online

Sialidosis type 1 and 2 MAIRE Online

Silver-Russell dwarfism TOUTAIN Online

Simpson-Golabi-Behmel syndrome TOUTAIN Online

Sjögren syndrome MANOUSSAKIS Online

Smith-Magenis syndrome De Leersnyder Pending

Spastic paraplegia, familial VALENTE Online

Spondyloepimetaphyseal dysplasia HALL Online

Spontaneous periodic hypothermia HAUSFATER Online

Stargardt disease DEUTMAN Online

Subpulmonary stenosis VOGT Pending

Subvalvular aortic stenosis HAUSER On line

Succinyl-CoA acetoacetate transferase deficiency FUKAO Online

Supravalvar aortic stenosis BOUVAGNET Online

Supravalvular aortic stenosis BOUVAGNET Online

Susac syndrome BARTOLUCCI Online

Systemic vasculitis (generic term) BARTOLUCCI Online

TAP deficiency FISCHER Online

Thrombocythemia, essential BRIERE Online

Toluene embryopathy ROBERT-GNANSIA Online

Townes-Brocks syndrome MARLIN Online

Tracheobronchomegaly CORDIER Online

Tracheobronchopathia osteoplastica LAZOR Online

Transcobalamin II deficiency KAMOUN Online

Triatrial heart ANDERSON Pending

Tricuspid atresia COOK Pending

Trimethylaminuria EUGENE Online

Triose phosphate-isomerase deficiency LIVET Online

Triple H (HHH) syndrome SAUDUBRAY Online

Troncus arteriosus malformation BALLERINI Pending

Tuberous sclerosis WOLKENSTEIN Online

Tyrosinemia type 1 SAUDUBRAY Online

Udd tibial myopathy PENISSON-BESNIER Online

Uhl anomaly GERLIS On line

Ulcerative colitis ARDIZZONE Pending

Univentricular heart ANDERSON Pending


Usher syndrome LORENZ Online

Valvular dysplasia of the child BONNET Pending

Vascular malposition SIDI Pending

Ventricular septal defect KACHANER Pending

Viscero-atrial heterotaxia (Heart situs anomaly included) ANDERSON Pending

Vitamin D resistant rickets GARABEDIAN Online

Waardenburg syndrome type 1 FAIVRE Pending

Waardenburg syndrome type 2 FAIVRE Pending

Waardenburg syndrome type 3 FAIVRE pending

Waardenburg-Shah syndrome TOURAINE Online

Wagner disease EDERY Online

Weaver syndrome DELAHAYE Pending

Wegener granulomatosis GUILLEVIN Online

Welander distal myopathy, swedish type PENISSON-BESNIER Online

Whipple disease FEURLE Online

Wilson disease BARTOLUCCI Online

Xanthinuria SIMMONDS Online

X-linked lymphoproliferative disease FISCHER Online

X-linked severe combined immunodeficiency, T- B+ DE SAINT-BASILE Online

ZAP70 deficiency NOTARANGELO Online

1.4 Content of the Encyclopaedia

The content of the ORPHANET encyclopaedia as of 30 November 2002 is:

Number of diseases: ...................................................3,547Number of summaries in French .................................. 990Number of summaries in English ................................. 833Number of long texts in French and English................. 445


2- The directory of servicesThe directory of services includes information on resources supposed to improve themanagement of rare diseases.

2.1 Management of the databaseThe database is hosted by the Orphanet Sun server located in Evry, suburb of Paris. Thedatabase management system is Sybase. There is a team of 2 computer scientists attached toit.The database can be accessed by each partner from its place. The rights are well defined andeach partner can only input on data from its country.

The overall data collection process is under the responsibility of a French informationscientist who is in charge of the training of all partners and of the internal quality control.

The collection of data is done by information scientists at the country level: 3 in France, 3 inItaly, 1 in Germany, Switzerland, Belgium Austria and Spain.

Each national partner is responsible for the following tasks: collecting, validating andentering in the database information on:

- clinical laboratories performing diagnostic tests for rare diseases ( type of test,protocol)

- on-going research programmes about rare diseases (title of the programme, name ofthe responsible scientist, address)

- patients' organisations dedicated to rare diseases (name of the association, president,address, text of presentation)

- specialised clinics dedicated to rare diseases

During the first year they were asked to establish their national methodology to do so andstart collecting a few data to test the interface. They were also supposed to translate all thethesaurus and the screens in their national language.

Each partner has been provided with the computer system tools to access and update thedatabase from their own premises. These tools have been developed by the central team andtested to be fully operational by the end of the first contract. A new version has been preparedduring the year of this contract and will be released by March 2003.

For the database of services, the tasks to be achieved during the second year were:- For the central team in Paris:

- to train the new partners (Spain and Austria)- to support the first partners in their activity of collecting, validating and formating

their data (Belgium, Italia, Switzerland and Germany)- to produce a new version of the database management tool, taking into account all the

difficulties observed during the feasibility study.-- for all the partners to agree on the quality scheme proposed by the co-ordinating team,

identify sources of information and start collecting data-- for all partners to establish a national scientific advisory committee, in charge of

validating their data before they are released in the database-- for Belgium, Germany, Italy ,Switzerland and Spain, to collect data on services and enter

them into the database- for Austria, to identify sources of information and send out questionnaires to collect data


--2.2 Country specificities

2.2.1 For ItalyDuring the year 2002, the Orphanet-Italia project developed according to the plans.Sources of information were identified through the Italian Ministry of Health, LearningSocieties and Patients’ Organisations networks.For data collection on clinical laboratories and outpatient clinics they started from themonitoring of the genetic testing in Italy, of the year 2000, carried out by CSS-MendelInstitute on behalf of the Italian Society of Human Genetics (SIGU, Dallapiccola et al.,Analysis 2002: 5/6, 292-360 ) and raised on-line (www.sigu.univr.it). The census hadcollected the results from 265 diagnostic laboratories, including 141 cytogenetic and 124molecular genetic labs. On the basis of these results they contacted each lab and clinicdirectors by e-mails, fax and phone calls sending them Orphanet forms for data collectionand formal consent. The same procedure was adopted to collect data on research projects.Concerning data on patients’ organisations a peculiar work of national investigationthrough web searching and personal contact was conducted, a total number of about 330patients’ support groups was detected in Italy.Identifying highly specialised outpatient clinics, located outside official Institutions, was avery hard task which is not yet fully completed. Patients’ organisations are helping withthis.

2.2.2 For SpainSpain´s resources concerning Rare Disorders and Orphan Drugs had not been previouslycollected in a comprehensive manner. In order to initiate the work for the development ofOrphanet in Spain three priorities have been established:1. The collection of data should be initiated with all data concerning Genetic disorders,including clinics, laboratories, research projects, clinical trials and patient associations. Thefact that genetic care and testing is not formally organised due to the absence of a GeneticsMedical specialty makes this task considerably difficult and time-consuming.2. The interest for Orphanet-Spain made necessary an immediate translation of all thecontents of the website and an initiation of the translation of the texts of the Encyclopaedia.3. An effort has been made in establishing contacts with national health authorities,learning societies, patient organisations and latin-american forums in order to inform themabout the emergence of Orphanet in Spanish.

2.2.3 For GermanyThe responsibility for Orphanet Germany was transferred from Pr. Clemens Müller,University of Würzburg, to Pr. Jörg Schmidtke, Hannover Medical School, in July 2002.All suitably qualified clinical laboratories in Germany have been contacted through letters,phone calls, and questionnaires. Currently, two thirds of all laboratories have agreed toregister, and the majority of these are entered into the database. We have establishedcomplete address lists of genetic counselling clinics, and, with the kind support of themajor umbrella organisation of patient support groups, the "Kindernetzwerk", of patientorganisations. Questionnaires adapted to the needs of counselling clinics and patientorganisations have been prepared and printed. We are now in the process of distribution.The only difficulty encountered was the reluctance of some laboratory directors to entertheir test offers in yet another database, with Germany already having a well establishedinformation system serving professional needs. Similar reasons may apply to thoselaboratories not having responded at all in spite of reminders (about one third). The

http://www.sigu.univr.it/


suggestion is to emphasize, in a prominent place on the Orphanet website, that Europe hasa well functioning reimbursement system among countries with a national health caresystem, that individual laboratories may recruit samples from other countries, particularlyin the case of highly specialized test offers, and to provide some guidance regardingadministrative procedures in trans-national reimbursements.

2.3 National Scientific CommitteesThe data about services are collected under the responsibility of national scientificcommittees. The composition of those which are already fully operational is the following :

2.3.1 French scientific committeePr François Bargy, pediatric surgeryPr Françoise Baud, toxicologyPr Nicole Baumann, adult metabolic diseasesDr Claudine Blanchet-Bardon, dermatologyDr Damien Bonnet, pediatric cardiologyPr Philippe Bouchard, endocrinologyPr Alexis Brice, adult neurologyPr Nicole Casadevall, hematologyDr Valérie Cormier-Daire, pediatric bone diseasesPr Martin Danis, parasitologyPr Pierre Delmas, adult rhumatologyPr Marc Delpech, biochemistryPr Louis Dubertret, dermatologyPr Denis Duboc, adult cardiologyPr Jean-Louis Dufier, pediatric ophtalmologyDr Béatrice Fervers, oncologyPr Alain Fischer, pediatric immunologyPr Alain Gaudric, adult ophtalmologyDr Marie Gonzales, foeto-pathologyPr Michel Goossens, molecular biologyPr Jean-Pierre Grünfeld, adult nephrologyPr Loïc Guillevin, internal medecinePr Xavier Jeunemaitre, cardiovascular diseasesPr Jean Kachaner, paediatric cardiologyPr Didier Lacombe, dysmorphologyPr Marion Leboyer, psychiatryPr Xavier Mariette, rheumatologyPr Patrick Niaudet, pediatric nephrologyDr Luc Paris, parasitologyPr Thierry Philip, adult oncologyPr Gérard Ponsot, pediatric neuromuscular disordersPr Anne-Marie Prieur, pediatric rheumatologyDr Elisabeth Robert, teratolologyPr Jean-Marie Saudubray, metabolic diseases (Chairman)Pr Olivier Sterkers, adult otorhinolaryngologyPr Andoni Urtizberea, neuromuscular diseasesPr Domnique Valla, hepatologyPr Gilles Vassal, pediatric oncologyPr Michel Vekemans, cytogenetics


Pr Jean-Louis Vildé, Infectious diseases

2.3.2 Swiss scientific committeeProf. Cem Gabay, RheumatologyDr Charles A. Haenggeli, Child NeurologyDr Michel Duchosal, HaematologyProf. Daniel Hohl, Dermatology/VenerologyProf. Claude Bachmann, Metabolic DiseasesDr Romain Lazor, PneumologyDr Armand Bottani, Medical Genetics /SSGMDr Christoph Meier, Endocrinology/DiabetesProf. J.-M. Jean-Michel Dayer, Allergy & ImmunologyDr N. Guertler, OtolaryngologyDr Hans Jung, Neurology

2.3.3 Italian scientific committeePr Giorgio Federici, Rome, Biochemistry:Pr. Antonio Pizzuti, Rome, Molecular Biology:Pr. Filippo Crea, Rome, Cardiology:Pr. Orsetta Zuffardi, Milan, Cytogenetics:Dr. Giovanna Zambruno, Rome, Dermatology:Dr. Cristina Digilio, Rome, Dysmorphology:Pr. Vincenzo Trischitta, San Giovanni Rotondo, Endocrinology:Dr Angelo Andriulli, San Giovanni Rotondo, Gastroenterology/Hepatology:Pr. Bruno Dallapiccola, Rome, Genetics:Pr. Roberto Foà, Rome, Haematology:Pr. Ferdinando Dianzani, Rome, Infectious diseases:Pr. Sebastiano Filetti, Rome, Internal Medicine/Rheumatology:Dr. Carlo Dionisi-Vici, Rome, Metabolic diseases:Pr. Gianfranco Rizzoni, Rome, Nephrology:Pr. Serenella Servidei, Rome, Neurology:Dr Enrico Bertini, Rome, Neuromuscular disorders:Pr. Francesco Guzzetta, Rome, Neuropediatric diseases:Pr. Lucio Luzzatto, Genoa, Oncology:Pr. Rosario Brancato, Milan, Ophtalmology:Dr. P. Bagolan, Rome, Pediatric Surgery:Pr. Gasperino Paone, Rome, Pneumology:

2.3.4 German scientific committeePr. Hanefeld, Göttingen, neuropediatrics and metabolic disease (chairman)Other nominations are on the way

2.3.5 Spanish scientific committeePr Pérez Jurado. Barcelona, GeneticsPr Mascaró. Barcelona, Dermatology:Dr. Font, Barcelona, Internal Medicine/Dermatology:Dr. Campos Castelló. Madrid, Neuropediatrics.Pr. Fernández Delgado. Valencia, Oncology..Pr. Tovar. Madrid, Paediatric Surgery.


Dr. García Alix. Madrid, Neonatology.Pr. Vicente Molina. Barcelona, General Pediatrics.Dr. Xavier Estivill, Barcelona, Molecular Genetics.

2.4 Current content of the database of servicesThe current version of the database includes information on specialized clinics, clinical labs,research projects and patients organization. The content of the database as of 30 November2002 is:

- Number of clinical laboratories ........................................................................ 537- Number of diseases with a diagnostic test ........................................................ 830- Number of research programmes ................................................................... 1347- Number of disease with a research programme ............................................... 933- Number of types of clinics ............................................................................... 131- Number of highly specialised clinics................................................................ 882- Number of support groups ............................................................................... 480- Number of diseases linked to support groups ................................................ 1280- Number of support groups with a website ........................................................ 392- Number of website hosted by ORPHANET ...................................................... 62- Number of professionals cited ....................................................................... 3036- Number of diseases linked to a website ......................................................... 1320- Number of distinct Url .................................................................................. 2972- Number of orphan drugs ................................................................................... 195

Including:- 25 drugs with a European marketing authorisation- 86 drugs with an American marketing authorisation- 19 drugs with a Japonese marketing authorisation- 29 drugs with an Australian marketing authorisation

- Number of disease linked to an orphan drug ................................................... 195

2.5 The quality charterAll the partners have agreed on a quality charter do be respected by all partners during ameeting held in Paris on 5-6 February 2002.

General principles- ORPHANET is committed to maintain, update and develop an Internet

database dedicated to rare diseases and orphan drugs.- ORPHANET is committed to maintain an access that is both free and free

of charge.- Collection of data and dissemination of information abide by the legal

provisions in force in the countries concerned: the professional code ofethics, any law on computing and liberties, on intellectual property rightsand any law or regulation applicable.

- The information disseminated and the services developed comply with thecodes and recommendations issued by the ad hoc committees recognizedat the national or international level, especially concerning the respect ofpatients' rights, the respect of the information confidentiality, thepatrimoniality of medical information, the practice of on-line medicine,and the safety of networks.


- Up to now, the codes and charters to which ORPHANET has adhered arethe following: the HONcode(http://www.hon.ch/HONcode/Conduct.html), the eHealth Code of Ethics(http//ihealthcoalition/org/ethics/ehcode.html), the "Guidelines for Medicaland Health Information Sites on the Internet" from the American MedicalAssociation (http//pubs.ama-assn.org/ama_web.html) and therecommendations from the French National Board of Physicians (ConseilNational de l'Ordre des Médecins).

- The database is under the responsibility of a scientific committee and aneditorial board whose members are appointed for their expertise in thediseases considered on the proposal of the learned societies, the healthauthorities of the countries involved or any relevant organization. All theinformation available to the public is validated by a member of thecommittees before it is put on line.

- All the information is updated as often scientific news require it or at leastonce a year for all the data, including the administrative data.

- The methods used to collect and validate the data are described below.The mention “Central Registry (CR)” means that the procedure is operatedexclusively at the Paris team level. The mention “National Registry (NR)”means that the procedure applies for every partner, including France.

Languages- Orphanet is a multilingual project. The common language between

partners is English.- The Central Registry is in charge of maintaining the database in French

and English.- Some National registries are in charge of providing translations in their

national language (Germany for German, Spain for Spanish, Italy forItalian).

Inclusion of diseases (CR)- The list of diseases which are included in ORPHANET is defined as any

condition, no matter its origin, which has a prevalence lower than 1 in2,000 in the European population.

- The list is established by the central registry. All suggestions to create anew disease entry or delete an existing entry, or re-organize theclassification must go to David Oziel ([email protected])

- Each disease is described by a name, synonyms, key-words using theMESH terminology. Any suggestion as to modify the name, synonyms orkey-words attached to a disease should also go to David Oziel.

- The NRs are responsible for the translation of these elements in theirNational language if different from French and English. The centralregistry maintains the list in English and French

- Each disease is classified by medical specialty and placed under theresponsibility of a scientific editor who is a recognised expert at theInternational level.

- There is at least one editor per medical specialty at the European level.The European experts form the European editorial board which is incharge of the Encyclopaedia.


- Preferably there is also one expert par specialty at the NR level. Theseexperts form the National scientific advisory board which validates thedata on services.


Textual information on each disease (CR)- Each disease is associated with a text summarising the main characteristics

of the disease, its prevalence, cause, prognosis and treatment.- Every text is signed and dated.- The writer is selected by the scientific editor or is the scientific editor.- For very rare diseases the text is written directly by the CR.- All the texts are submitted for validation to the scientific editor in charge

of the disease before its release.- The texts are updated at least once a year, and more often if new relevant

scientific facts are published.- The texts are written in an English which is understandable by any non-

specialist healthcare professional.- All the texts are written in English.- The summaries are translated in French by the CR. Translation of the

summaries in other languages has to be envisaged at the NR levelproviding that funding is obtained (average cost: 0.15 Eurocent per word;200 words per summary)

- The editorial process is managed by scientific editors working at the CR.

Research projects (NRs)- The research projects are identified using all the sources of information on

research projects financed after a competitive process and a scientificevaluation.

- At the European level, the projects are those financed by the EuropeanCommission.

- NR have to establish the list of their National funding agencies. For Francethese sources are: INSERM, CNRS, Universities, Ministry of health andCharities like the AFM.

- The researchers are then approached to give their consent to be listed inthe database and to precise the list of diseases which applies to theirprogramme.

- The list of research projects is updated once a year.

Clinical laboratories (NRs)- Clinical laboratories performing tests to diagnose rare diseases (no matter

the methods) are identified using all the sources of information such aslists of the Ministry of Health, National reference centres, lists ofprofessional organisations, lists established by patients support groups,lists suggested by the scientific editors.

- A questionnaire is sent to these laboratories to precise the type of activity,the methods used, the list of diseases which are diagnosed and obtain theformal consent of the responsible person.

- All the data are validated by the National scientific expert of the relevantspecialty before being released. They are updated once a year.


Specialised clinics (CR and NRs)- Types of clinics which are relevant for each disease are defined by the CR.

Suggestions can be sent by the NRs.- List of clinics of each type are established by the NRs, using all possible

sources.- A questionnaire is sent to potential clinicians to precise the type of their

activity, and obtain their formal consent.- For highly specialised clinics, the responsible physicians have to provide

evidence of their expertise (list of publications, total number of patients,number of new patients per year).

- All lists are submitted to a National expert.- These lists are updated once a year.- Only comprehensive lists of clinics can be released (matter of fairness).

Clinical trials (NRs)- The on-going clinical trials for rare diseases are identified using all

possible sources of information (partnership with academic and industrialsponsors, partnership with National drug agencies, web search,notification by experts, support groups and scientific societies)

- Both the sponsors and the principal investigators have to be approached togive their consent to be listed in the database and to precise the diseasewhich applies to their trial.

- The list of clinical trials is updated at least once a year and automaticallywith the closing date.

Registries/ database of patients (NRs)- Registries/ database of patients are identified using all the sources of

information ( notification by experts, research projects, support groups)- At the European level, the projects are those financed by the European

Commission.- The responsible persons are then approached to give their consent to be

listed in the database and to precise the list of diseases which applies totheir registry.

- The list of registries is updated once a year.

Networks (NRs)- Networks of professionals organized around a rare disease or a group of

diseases are identified using all the sources of information ( notification byexperts, research projects, support groups).

- Only networks which are funded or administratively identifiable, are put inthe database.

- At the European level, the projects are those financed by the EuropeanCommission.

- The responsible persons are then approached to give their consent to belisted in the database and to precise the list of diseases which applies totheir network.

- The list of networks is updated once a year.


Support groups (NRs)- Support groups are identified using all relevant ways including a web

search and a partnership with Eurordis.- The presidents are contacted to get their permission and establish the scope

of diseases attached to their activity.

Orphan drugs (CR)- All Orphan approved (in the US, Japan, Europe) drugs or non-orphan

approved drugs with a specific indication for a rare disease are put in thedatabase.

- The lists are established using the information available at the relevantgovernmental agencies.

Web sites (CR)- Each disease is linked to relevant other web sites.- Each web site is evaluated for its relevance, consistency, credibility.- The URL addresses are re-checked once a month.- The web sites are listed with a comment on the language used and a

description of the type of information which may be expected.- Only sites run under the responsibility of a public agency or a non-profit

organisation are listed.- NRs care invited to suggest National websites to Severine Rastoul

([email protected]) corresponding to the above definition.

Design charter(CR)- There is a design charter which has to be respected.- The Orphanet logo is put on all documents used to run the activity.

European Website (CR)- There is a European website at the address:www.orpha.netwhich is

placed under the editorial responsibility of the CR.- Other URL have been bought. They redirect towww.orpha.net. Their list

is annexed.- The static pages on the European website give general information on rare

diseases, orphan drugs, the Orphanet project, the ethics charter and theprocedures.

- These texts are maintained in French and English by the CR. They aretranslated into National languages by the NRs.

National Websites (NRs)- NR may establish a National website of their own to give additional

information which is only relevant at the country level.- The address of the National website has to be www.orphanet.it/de/be…..- National web sites respect the design chart and the logo- Their front page has to give access to the CR website.

Logos- The front page of the European website contains logos of all the agencies

providing funding for the European project.

http://www.orpha.net/

http://www.orpha.net/


- The front page of the National websites contains logos of all agenciesproviding funding for the National projects.

2.6 Local teams: composition and training

2.6.1 French teamThe French team is composed of 12 persons:Project Director: Ségolène Aymé who is a medical geneticist, director ofresearch at the INSERMInformation scientists: Mounia El Yamani, Caroline Hagnéré, Anne-SophieLeGall, David Oziel, Nathalie Piroux, Séverine RastoulComputer scientists: Bruno Urbero, Nguyen Manh Hung, Jean-Pierre BarbeitosAssistant: Valérie FontenySecretary: Sandrine Gromat

2.6.2 Italian teamThe team includes 6 persons (4 medical doctors, 2 computer scientists, 1 editorialassistant):Project Director: Pr Bruno Dallapiccola;Medical geneticist and project supervisor: Dr Rita Mingarelli;Medical geneticist, in charge of research projects and outpatient clinics: Dr Anna Sarkozy;Medical geneticist, in charge of clinical laboratories and patients organisations: Dr DanielaZuccarello;Database coordinator, in charge of translation and data entry: Dr Roberta Ruotolo;Computer scientists: Dr Guendalina Capece, Dr Roberto Cespa.The team was trained by the coordinating team to use the database methodology throughtwo visits in Paris (on February and July2002), e-mails and phone calls.

2.6.3 Belgian teamThe Belgian team is composed of two persons:Pr Jean-Pierre Fryns, country coordinator, who is a medical geneticistMrs Veerle Govers who is in charge of the data collectionThe Belgian team has been trained in october 2002.

2.6.4 Austrian teamThe Austrian team is composed of two persons:Pr Gert Utermann, country coordinator, who is a molecular geneticistDr Birgit Kunz , who is in charge of the data collection.The Austrian team will be trained in march 2003.

2.6.5 German teamThe Orphanet Germany team consists of:Pr. Jörg Schmidtke, coordinatorDipl. Biol. Kathrin Rommel, information scientist.Pr. Schmidtke is head of the Institute of Human Genetics at Hannover MedicalSchool and is chair of Human Genetics. He has a long scientific record in themolecular genetics of human inherited disease. Kathrin Rommel has a Diploma(Master's Degree) in Biology and is in the process of submitting her PhD thesison molecular genetic studies of fibrillinopathies. In November 2002 sheattended a one week training course in Paris. Under the guidance of the


Information scientists David Oziel she aquired the basis knowledge of theapplication programm “Major2 V2.4” which is currently in use for enteringdata into the Orphanet database.

2.6.6 Spanish teamThe team in Spain is composed of four members. Two pre-doctoral researchersPilar Sancho and Jesus Del Valle are dedicating 70% of their time to the projectand are funded by Orphanet. 30% of their time is dedicated to Doctoral coursesand integration in the common educational tasks of the Department. Theiractivities are mainly related to the collection and entry of data and initialpreparation of part of the text translations. Pilar Sancho attended a 3 daytraining period in Paris with French team, in November 2002.The coordinator for Spain, Dr. Miguel Del Campo is a geneticist andpediatrician. He has mainly been in charge of organising the distribution oftasks, attending the Orphanet organisation meetings in Paris, Strasbourg andRome, supervising all translated material, translating personally many texts andorganising the dissemination of the project at the country level. Dr. PérezJurado, head of the scientific advisory board has initiated the task of recruitingthe scientific advisors for Spain and contributed substantially to the translationprocess.

2.6.7 Swiss teamThe Swiss teamis composed of :Pr Célia Blanchet-Delozier, the Swiss Orphanet Supervisor, who is a geneticistOlivier Menzel (PhD student), in charge of the data collection/insertionTelassim Alberti, WebmasterThe Swiss team has been trained in october 2002.


3- Collaboration Orphanet / Eurordis

During the past year, discussions went on with Eurordis regarding a possible collaboration.They ended with a formal agreement which is the following:

“Letter of intent - Collaboration between Eurordis and Orphanet on Eurordis Portal

Further to several contacts heading in the meeting of September 4th, 2002 in the framework of the PARD 2project, it has been decided to reinforce the collaboration between Orphanet and Eurordis around the newEurordis portal and the Orphanet website through the search for synergies and complementary approaches in thebenefit of users.

Within the PARD 2 project"New communication technologies (website) to the service of the rare disordersnetwork and sharing of good practices in different help services to patients, already existing in Europe (hotline)" this collaboration will be implemented in various areas:

1. Directory of patient organisationsThe directory of patient organisations designed and updated by Orphanet will be complemented with additionalfields and with information from countries with no Orphanet team.Right now the information displayed on associations and organised by disease includes name of association,president name, address, telephone, link to web page. Added fields could include the main types of actions andservices (clickable list of max. 10 items) or information on existing patient groups.

Orphanet will:• enable the access to the database from both websites• increase the number of fields to fit with Eurordis needs• give full responsibility for data collection and data release to partners in countries not yet covered by

Orphanet national teams• provide tools to update the database from these remote sites• provide training to the partners on how to use the toolEurordis will• identify possible partners in new countries and cover costs implied by training in Paris• identify possible partners in countries already covered by Orphanet to work with the national Orphanet

teams.The job of the partners would be to:• be trained to the updating tool and to the procedures to be followed• identify associations concerned in their country• send them a questionnaire• check the diseases covered• punch the data• update the data once a year• liaise with an Orphanet or a Eurordis employee for any issue.

Forecasted implementation timing: from December 2002 to January 2003 for database changes, 2003 onwardsfor integration of data from new countries

2. Links between the two websitesWhenever possible links will be built between the two websites to avoid duplication and increase exchanges.Forecasted implementation timing: from December 2002 on an ongoing basis

3. Content buildingOrphanet agrees to cooperate with Eurordis on content pages of the Eurordis website and links to usefuldatabases.Forecasted implementation timing: from December 2002 on an ongoing basis


This collaboration will be further extended in the second quarter of 2003 within the PARD 3 project"Pan-European Patient Network for Information on Rare Diseases and Orphan Drugs"and the development of theEurordis portal.In particular four areas of collaboration in that framework could be:

a) collaboration on the development of forumsOrphanet and Eurordis will start a discussion to develop guidelines for managing forums (like rules for acceptingor refusing a message and possibly for changing the title of a message to improve understanding…) and tocommission a specialist for programming such a tool. On a case by case basis, forums could be identified asOrphanet only, Eurordis only, or showing both logos and being accessible from both sites.

b) common access to an event management interface

c) the extension to other European countries of the NESTOR computer system, presently implemented in France,giving associations or national alliances the possibility to build and host their websites free of charge;

d) the joint development of a tool to facilitate individual contacts between isolated patients/persons with veryrare diseases.

The two partners will also invite a member of the other organisation to meetings discussing topics of potentialmutual interest.

Paris, December 24th, 2002(issued in two original copies)

Yann Le Cam Ségolène AyméChief Executive Officer Scientific DirectorEurordis Orphanet

4- Dissemination of results

4.1 Statistics of the serverThe usefulness of the database was supposed to be done through the number of connectionsper day, number of different sites, number of countries, length of connections, types ofrequest and analysis of messages received.

The number of connections is increasing regularly as shown on the following figures:


Fig 1 : Number of sites

31 000 33250 35500 40000 42000 44500 46500 48500 53000 55500 58000

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Fig.2 Number of files

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The current website is visited every day by 3,500 different people from over 110 countries.

A survey about the identity of the users was implemented in September 2002. It gave thefollowing results:

The visitors are:- the patient it self (18.5%)- the parents of a patient (11.5%)- a family member (15.2%)


- MD-hospital-based (14.9%)- MD-private practice (8.3%)- experts in the field of rare diseases (3.6%)- non MD healthcare professionals (13.5%)- other type of professionals (6.5%)- others (8%).

4.2 List of invited conferences given by Orphanet partners:

4.2.1 Conference by Ségolène Aymé for Orphanet:« Orphanet : une réponse adaptée à la problématique des maladies rares » Journéenationale du comité français pour la scolarisation des enfants et adolescents atteints detroubles de la santé. CNEFEI, Suresnes, 5 Décembre 2001

« La E-santé : un exemple de succès avec l’internet au services des maladiesorphelines » Colloque Initiative Net Santé, Paris, 13 Décembre 2001

« L’utilisation d’Internet dans le secteur social de la santé : l’exemple d’Orphanet »Séminaire au Mastère d’E-business d’HEC. 12 Février 2002

« Maladies orphelines ou la solitude des malades » Bar des Sciences. Café « Le pèretranquille », Paris. 6 Mars 2002

« L’épidémiologie des maladies rares » MEDEC, Paris, 14 Mars 2002

« L’état de la Recherche sur les maladies rares : freins et opportunités » Séminaire del’IFR 02 Institut Claude Bernard, Paris, 22 Mars 2002

« L’internet au service des maladies rares : l’expérience d’Orphanet » Séminaires del’Institut Gustave Roussy, Villejuif. 14 Mai 2002

“Information scientifique et intelligence économique : l’exemple d’Orphanet et desmédicaments orphelins”. Forum Benchmark e-Pharmacie, Paris, 23 Mai 2002

“Provision of genetic services in Europe”. European Society of Human Geneticsmeeting. Strasbourg, 27 May 2002

« Maladies rares et médicaments orphelins : l’expérience d’Orphanet » Réunion del’Amical des Praticiens Conseil de la CNAMTS ; Paris , 28 Mai 2002

« Maladies rares et médicaments orphelins » Journées annuelles de Association pourl’Information et le Recherche sur les Maladies Génétiques. Paris , 2 juin 2002

“Unequal access to genetic services in Europe”. European Rare Diseases AwarenessConference, Barcelona, Spain, 14 June 2002

“Recent European Initiatives on Platform development for Rare Diseases”. DIA annualmeeting, Chicago, USA, 19 June 2002

“Hereditary inflammatory disorders in Orphanet”. Third International Conference on


Familial Mediterranean Fever and Hereditary Inflammatory Disorders. La GrandeMotte, Septembre 26 2002

“Importance of Orphan Medicinal Products. Health Insurance in Transition”. 5thInternational Conference. 28 September 2002, Zagreb, Croatia

“Les plateformes au service de la recherche clinique dans les maladies rares”. ColloqueINSERM : « Maladies rares et Recherche clinique :Optimiser les moyens etl’environnement pour accélérer le développement de thérapies innovantes ». Paris,Vendredi 11 Octobre 2002

“Nouvelles technologies de l’information et de la communication et les maladies rares:une longue histoire”. Colloque “NTIC, pathologies chroniques et professionnels desanté” InetSanté. Paris, 22 octobre 2002

“The Orphan Drug Regulation: its impact on innovation in the European Union”. Thirdworkshop on partnering for rare disease therapy development: From research todevelopment: from bottlenecks to solutions. Rome, 24 October 2002

“ Impact of an Internet-based information service on rare diseases on the uptake ofhealth care services : the Orphanet initiative” . Annual meeting of the InternationalSociety for Quality in Health Care, UNESCO, Paris, November 7,2002.

4.2.2 Conference by Miguel Del Campo for Orphanet-Spain :

« The Orphanet database:an online resource for rare diseases »Departament de Cièncias Experimentals i de la Salut. Universitat PompeuFabra, Barcelona. 17 May 2002

« Orphanet : an encyclopaedia of rare diseases »Grupo de Pediatría. Institut Universitari Dexeus. Barcelona, June 11 2002

« The Orphanet database:an online resource for rare diseases »Universitat Pompeu Fabra. Facultat de Cièncias de la Salut i de la vida.Aula 101. Barcelona Tuesday, September 24th 2002

« Orphanet : a tool to manage rare diseases »Sociedad Catalana de Pediatría. Academia de Cièncias Médicas de Barcelona.Reunión del grupo de Dismorfología. Monday October 7 2002.

4.2.3 Conferences by Celia Delozier for Orphanet-Switzerland

“Orphanet: a database of rare diseases”Swiss Society of Medical Genetics, 15 April 2002.

The Orphanet project was also presented to the quarterly meeting of the SIAK Network(Swiss Network for Cancer Research and treatment) in April 2002.

4.2.4 Conferences for Orphanet Italy


"Supporti informatici per le malattie rare".Congresso Malattie Genetiche Rare, Messina 23 November, 2002 - Dr Rita Mingarelli:" Nuove prospettive della Genetica e della Biologia Molecolare".58° Congresso dellaSocietà Italiana di Pediatria, Montecatini 28. September-2 October, 2002 - Pr BrunoDallapiccola:

4.2.5 Orphanet booth at the Annual meeting of the European Society of HumanGenetics in Strasbourg, FranceOrphanet got a booth at the Annual meeting of the European Society of HumanGenetics in Strasbourg, France (25-28 May 2002). This meeting is attended by 1,500participants. 300 of them have visited the booth. Many potential collaborations withother European and eastern countries have been identified.

5- Acknowledgement of the EU financial suport

The Eu funding is mentioned on the Orphanet website. The logo of the Europeancommission is on the front page of the site. The funding is mentioned in the pagesdescribins the project, as shown on the figures below:




6- Conclusion

The Orphanet project is developing according to the plans. The first year was a very busy onewhich permitted to explore all the difficulties for transmitting our five-year experience withdata collection. The procedures are now well in place and should be easily adopted by thenew partners.

The experience also clearly showed to the partners that there was a great need in gettingnational funding to expand the local teams. Several countries are on the way of havingcomplementary funding.

Many more countries would like to join, especially countries from eastern Europe. We arewilling to incorporate them into the network if the corresponding funding is identifyed.

This report was produced by a contractor for Health & Consumer Protection Directorate General and represents the views of thecontractor or author. These views have not been adopted or in any way approved by the Commission and do not necessarilyrepresent the view of the Commission or the Directorate General for Health and Consumer Protection. The EuropeanCommission does not guarantee the accuracy of the data included in this study, nor does it accept responsibility for any use madethereof.

Documents

Programme of community action on rare diseasesec.europa.eu/health/ph_projects/2001/rare_diseases/fp_raredis_2001... · Programme of community action on rare diseases Contract 2001/CVG4