17 January 2015 print
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2014, a dynamic year for rare disease stakeholders
With the new year comes new beginnings, resolutions and wishes for the future, but this moment also offers the opportunity to review the previous year’s achievements. 2014 was both a busy and fruitful year for the rare disease community, punctuated with a number of major events bringing together old friends and new from across stakeholder groups and from the four corners of the globe, the 2014 European Conference on Rare Diseases in Berlin and Orphan Products and the International Rare Disease Research Consortium’s second conference in Shenzhen.

2014 saw the first meeting of the European Commission Expert Group on Rare Diseases, which replaced the European Union Committee of Experts on Rare Diseases. This multi-stakeholder group, has a mandate to aid the Commission with the development and implementation of rare disease policies. The Commission outlined its future priorities for the field of rare diseases in its implementation report, published in Autumn 2014, which took stock of the achievements following the implementation of the Commission Communication : Rare Diseases Europe’s Challenge (2008) and the Council Recommendation on an Action in the field of rare diseases (2009). In particular, the report highlighted the adoption of 16 national plans/strategies in Member States by the December 2013 deadline defined by the Recommendation: 4 additional plans were adopted in 2014 making the total 20 to date. The report concluded with a list of actions envisaged in the future year by the European Commission, which included the intention to maintain the EU’s coordinative role in the development of European policy on rare diseases and to support national activities, including plans and strategies for rare diseases. In addition, the Commission voiced their intent to continue support to the IRDiRC and initiatives developed under its umbrella and to play a role in collaborating with important international stakeholders in the field of rare diseases. Support to ensure proper codification of rare diseases was also cited as a priority as was support to increasing public awareness of rare diseases and patient empowerment. Finally, the Commission highlighted that much work would be carried out concerning the implementation of the Directive on cross-border healthcare including support to the development of tools to faciltate the cooperation and interoperability of European Reference Networks for rare diseases.

The Expert Group on Rare Diseases will provide support to the European Commission in the implementation of these goals. The Expert Group met three times in 2014 and adopted in its last meeting of the year a first recommendation on improving the codification of rare diseases which marks an important step forward in ensuring that rare diseases are made visible in health information systems through the use of Orphacodes when no appropriate specific code exists in current coding systems. Next steps to ensuring a coherant and integrated strategy in the field of coding of rare diseases will be pursued by the future Joint Action for Rare Diseases to start in 2015 which will support rare disease activities at European level, including Orphanet and the activities of the Expert Group.

The Expert Group was supported in its endeavours in 2014 by the EUCERD Joint Action through which a range of expert workshops were organised on the themes of quality of care for rare diseases and centres of expertise, European Reference Networks, national plans/strategies for rare diseases, trans-border genetic testing, evaluation of rare disease health projects and Orphacodes. Five national conferences were co-organised by Eurordis and National Alliances of rare disease patient organisations throughout Europe in the scope of the Joint Action with the aim of promoting the elaboration and implementation of national plans/strategies for rare diseases (consult the available conference reports).

At the European level, 2014 also saw the launch of the a much anticipated ontology of rare disases which represents an all-inclusive and singular resource point for the ontological analysis of rare diseases. The Orphanet Rare Disease Ontology (ORDO), jointly developed by Orphanet and the European Bioinformatics Institute (EBI), provides a structured vocabulary for rare diseases, capturing relationships between diseases, genes and other pertinent features, in a language directly understandable by computers. ORDO is available to all on the sites of BioPortal, EBI as well as Orphadata.

2014 was a year rich in rare disease events, kicked off by the highly successful international Rare Disease Day on 28th February 2014. Last year marked a record high of 84 participating countries and 410 events around the world: 9 countries participated for the first time (Cuba, Ecuador, Egypt, Guinea, Jordan, Kazakhstan, Kenya, Oman, and Paraguay). EURORDIS, organiser of the day, held a policy event in Brussels to mark the day. The 7th European Conference on Rare Diseases and Orphan Products was held in Berlin from 8-10 May bringing together 750 participants from over 40 countries, providing an excellent networking opportunity and the time to share experiences and explore new horizons. Taking stock of achievements and future endeavours to improve the quality of life of people with rare diseases, the conference report, presentations, and abstracts from the conference cover a range of interesting themes, ranging from healthcare services to research, from orphan products to approaches beyond medical care.
Another major event was the much awaited 2nd International Rare Diseases Research Consortium (IRDiRC) conference which took place in Shenzhen, China on 7-9 November 2014. Organised by IRDiRC in partnership with BGI, the conference brought together over 600 rare disease stakeholders from all over the world to discuss and share experiences and expertise. The main theme of the conference was collaboration, placing emphasis on contributing towards expertise, information and technology via global networks to improve diagnosis of rare diseases, patient access to best treatment and care, and patient and family support. IRDIRC promises to contribute to the development of 200 therapies for rare disease and means to diagnose all of them by 2020, which can only be possible through the collaborative efforts of academics, researchers, clinicians, industry leaders, policy makers and patient advocates, internationally.

In terms of support to the IRDiRC’s aims, the European Commission started to launch previously announced calls for proposals, including the continuation of the activities of the E-Rare ERA-Net on rare diseases which funds joint transnational calls between European funding bodies: this coordination activity was assured for the period of 2014-2019.
In the field of orphan medicinal products, 2014 saw a record number of orphan designations and market authorisations in Europe and the USA. At European level, the European Medicines Agency’s Committee on Orphan Medicinal Products (COMP) granted 196 positive opinions for orphan drug designation out of 259 examined submissions, and the European Commission granted 160 designations. Twelve products were granted marketing authorisation at European level in 2014 (consult the COMP’s meeting report of December 2014).
In the US, the Food and Drug Administration (FDA) reached a milestone with a record 49 approvals for rare diseases, with 467 designation requests (a nearly 35% increase over 2013), and 293 orphan drug designations grants, which constitutes approximately 13% increase over 2013). Although this provides an excellent incentive to developers of orphan drugs, they often carried with them a price tag that remains unaffordable by many rare disease patients.

What are the hopes of the ever advancing rare disease community at the start of this new year? As at the end of each year, there is cause for both pessimism and optimism. The rare disease field remains politically dynamic, but the biggest challenge for the year ahead will be the successful implementation of national plans and strategies for rare diseases in the current economic context. Limited resources, both at European and national level, will mean that priorities will have to be established and creative solutions will have to be imagined to ensure that the goals proposed by these initiatives can be reached. Scientific discoveries continue to accelerate in the field of rare diseases, bringing with them a wealth of new knowledge to be applied in order to improve the day to day lives of those living with a rare disease.

EU Policy News
EMA chooses six medicines in the first phase of the adaptive pathways pilot project
EMA launched the adaptive pathways pilot project in March 2014. The adaptive pathways approach (formerly known as adaptive licensing), is part of the Agency’s efforts to improve timely access for patients to new medicines. The concept of adaptive pathways foresees an early approval of a medicine for a restricted patient population based on small initial clinical studies. EMA has received 34 requests from companies to include their medicines in the adaptive pathways pilot project up to the beginning of December 2014, the medicines covered a broad range of therapeutic areas. Following review and discussion with companies, six medicines have so far been selected to go forward into more in-depth discussions with the company with the participation of all stakeholders, including health technology assessment (HTA) bodies and patients’ representatives. Applicants are invited to contact EMA (adaptivepathways@ema.europa.eu) for advice on the content and suitability of their request to be considered for stage II of the pilot.
Read the press release on the EMA website

National & International Policy Developments
Other European news
Telethon 2014 collects a record amount of € 82,353,996 in France
The Telethon in France ended on 7 December, 2014 with the counter showing € 82,353,996. This impressive fundraising effort has been applauded by the four families with children combating a rare disease as well as the researchers. On behalf of the families and researchers, AFM Téléthon thanked the sponsor - Garou, the children, volunteers, partners, artists, animators and, France Télévisions for the device exception made for the 28th Telethon. For 30 hours, the France Télévisions channels settled at the feet of the brillian Eiffel Tower in Paris, as well as in Metz, Perpignan, Marseille, Valves and Guadeloupe to bring on the extraordinary success of the 28th edition of the Telethon.
Go to the France2 website

Health care burden of Duchenne and Becker muscular dystrophies in Germany
A study published in the Orphanet Journal of Rare Diseases, determined the burden of Duchenne (DMD) and Becker (BMD) dystrophy in Germany. Both these dystrinopathy causes progressive disability leading to "reduced working capacity and high health care utilisation". The authors utilised a micro-costing method to examine the direct as well as indirect costs borne by patients, relatives, payers and society, to measure and compare the economic burden of DMD and BMD in Germany. The authors estimated that the annual disease burden including direct medical/non-medical, indirect and informal care costs of DMD was € 78,913 while total costs in BMD was € 39,060. The authors noted that loss of productivity and absenteeism of patients/caregivers as well as medical costs of rehabilitation services and medical were the most important indirect cost drivers and that the total costs increased with disease progression and clinical severity. The authors believe that “early assessments of economic aspects and the disease burden are essential to gain extensive knowledge of a distinct disease and above all play an important role in funding drug development programs for rare diseases”.
Read the open access article

Socioeconomic burden of 10 Rare Diseases in Europe
Health Policy published a review of where lack of research on the socioeconomic cost, direct and indirect, for 10 rare diseases in the context of the BURQOL-RD project (“Social Economic Burden and Health-Related Quality of Life in patients with rare diseases in Europe”) was presented. The 10 rare diseases included Cystic Fibrosis, Duchenne Muscular Dystrophy, Fragile X syndrome, Haemophilia, Juvenile Idiopathic Arthritis, Mucopolysaccharidosis, Scleroderma, Prader-Willi Syndrome, Histiocytosis and Epidermolysis Bullosa. The authors found that the level of existing evidence is highest for diseases with available drug treatments and is not necessarily associated with disease rarity. They also found that cost evidence on rare diseases appears to be very scarce, with Cystic Fibrosis and Haemophilia being relatively well studied, compared to the other conditions and total lifetime cost figures were found only across four diseases, and total annual costs (including indirect costs) across five disease. Although methodological variations prevent any detailed comparison between conditions, most of the rare diseases examined are associated with significant economic burden, both direct and indirect. Most of the rare diseases examined in this study are associated with significant economic burden. Indirect costs associated with loss of productivity in most cases approach or exceed the level of direct costs. The study also revealed methodological issues related to the comparability of the available evidence across borders which need to be addressed in future research.
Consult the abstract

High economic burden associated with systemic sclerosis in France
A study published in the Scandinavian Journal of Rheumatology provided data on the economic burden and health-related quality of life (HRQoL) associated with systemic sclerosis (SSc) in France and to raise awareness of the repercussions of this disease for patients and caregivers and on the health and social care system. The HRQoL patients of 147 patients recruited through the Association des Sclérodermiques de France (ASF), the French association for SSc patients, and caregivers was assessed with the five-level EURQol-5 Dimension (EQ-5D-5L) health questionnaire. The average annual cost of SSc was estimated at € 22 459 per patient where “direct healthcare costs amounted to € 8452, direct non-healthcare formal costs to € 1606, direct non-healthcare informal costs to EUR 1875, and indirect costs resulting from patients’ absence from the labour market to € 10 526”. The main contributors to SSc costs were hospitalisations and early retirement. The authors concluded that the HRQoL for SSc are significant for both patients and caregivers in France, underscoring the need to develop tailored policies targeted at improving patients’ care and reducing the long-term impact of SSc.
Consult the abstract

11 centers designated as Genomic Medicine Centers to decode 100 000 genomes in the UK

Genomics England, a wholly owned Department of Health company, has been set up to deliver the latest “big genomics” venture, where 100 000 whole genomes from 75 000 patients and 25 000 genomes of tumours are to be sequenced by 2017. On Dec 22, NHS England announced that 11 centres across the country will become designated Genomic Medicine Centres to help deliver the targets of this project which focuses on rare diseases, infectious diseases, and cancer. According to researchers and clinicians, this ambitious but exciting project will require a huge amount of complex statistical analysis of huge amounts of linked clinical and molecular data marking the next era of bioinformatics in clinical research. Genomics England plan to use a new international system called Decipher which will link clinicians around the world and pool, with patients’ permission, anonymised data on multiple families with similar diseases to better understand genotype-phenotype relationships. Genomics England hopes researchers, clinicians, and those in training will collaborate with similar datasets in cancer and infectious diseases around the world. NHS will also work towards combating the ethical issues that may arise in a vast project such as security and protection of data as well as dealing with secondary or incidental findings.
Go to Genomics England website
Read the open access article - UK gears up to decode 100 000 genomes from NHS patient

Other International News
Health minister of Rajasthan, India promises help for rare disease patients
Speaking at the first stakeholders roundtable meet (RTM) undertaken by the Lysosomal Storage Disorders Support Society (LSDSS) India, the health minister of the state of Rajasthan in India - Rajendra Singh Rathore, has promised all possible support to patients with rare diseases. Rathore said the government would undertake a number of welfare initiatives, including setting up a committee, making treatment available under National Health Mission and making drugs available under the free medicine scheme, for such patients.
For more information

Alexion collaborates with University of Connecticut Stem Cell Institute to bring therapeutics to Rare Diseases
The University of Connecticut has announced a new stem cell research collaboration in the field of rare disease with Cheshire, Conn.based Alexion Pharmaceuticals Inc. The research collaboration will focus on the discovery and testing of therapeutic candidates to treat rare and disabling disorders for which there are currently no effective treatments. The collaboration will expand on the work of David Goldhamer, professor of molecular and cell biology and associate director of the University of Connecticut Stem Cell Institute. Goldhamer has identified the progenitor cell type that drives the pathology of a group of diseases, and has developed physiologically relevant disease models. These models will be used to further understand the pathophysiology of these disorders, and to test potential therapeutics.
For further information

Children's Rare Diseases Fund Launched in China
China Social Assistance Foundation (CSAF) launched the China Child Rare Disease Aid Fund in China National Children's Center in Beijing on Dec. 26, 2014. Considered to be the first special fund for minors with rare disease, the fund aims to help children with their sickness and at the same time establish a support system to boost their morale. The fund also plans to employ and give entrepreneurship assistance to the family members. However, the fund's main goal is to investigate the source of the diseases, create policies and regulations, cooperate in the international research about the disease, and enhance social harmony among children afflicted with disease. DeExpo President Zhang Yong donated 5,000,000 yuan (USD 804,531) on behalf of DeExpo.
Go to the China Social Assistance Foundation website

Funding Rare Disease Therapies in Australia
A report by the McKell institute in Australia has concluded that Australia’s system of funding rare diseases, conducted by the Life Saving Drug Program (LSDP), is in need of reform. This informative report highlights several challenges involved in bringing treatments for rare disease patients in Australia. The report identifies several problem areas including the fact that there is no common definition for rare diseases in Australia. The report also highlights that only two therapies, Kalydeco for Cystic Fibrosis, and Soliris for Atypical Hemolytic-Uremic Syndrome, are currently approved under Australia’s current program for rare disease therapies. Additionally, the report emphasises that Australian rare disease patients wait considerably longer than other western countries to access drugs, which sometimes could be as long as 8 years. The report makes five recommendations to overhaul the current program commencing with the formulation of a national strategy for rare diseases. Also recommended is flexibility in the analysis of cost-effectiveness and assessment of new therapies for rare diseases.
Read the report by McKell Institute

Guidance Documents and Recommendations
Evidence-based management of sickle cell disease: guidelines from the expert panel of the American Academy of Pediatrics
Consult the guidelines
To read more about "Sickle cell anemia"

Pediatrics ; 134(6):e1775 ; December 2014
Inherited epidermolysis bullosa: pain care practice guidelines
Consult the abstract
To read more about "Inherited epidermolysis bullosa"

BMC Medicine ; 12:178 ; November 2014
Huntington disease: technical standards and guidelines from the American College of Medical Genetics and Genomics
Consult the Pubmed abstract
To read more about "Huntington disease"
To read more about "Huntington disease"

Genet Med. ; 16(12):e2 ; December 2014
Friedreich ataxia: consensus clinical management guidelines
Consult the abstract
To read more about "Friedreich ataxia"

Orphanet Journal of Rare Diseases ; 9:184 ; November 2014
Bioinformatics, Registries and Data Management
Phenotip - a web-based instrument to help diagnosing foetal syndromes antenatally with sonographic markers
Incorporating ultrasound in routine prenatal care for foetal anomaly screening is essential as the detection of multiple foetal anomalies, and hence a possibility of a syndrome can be identified with further testing. However, none of the known databases include prenatal ultrasound findings in the search algorithm and deal poorly with prenatal marker synonyms, as they are mainly designed for postnatal use. An article published in the Orphanet Journal of Rare Diseases describes the development of a searchable database of foetal syndromes called Phenotip, which relies on antenatally diagnosable markers. The authors describe the construction of “a hierarchic tree of 1140 sonographic markers and submarkers, organized per organ system”, hence developing a database of syndromes that can be diagnosed prenatally. The authors believe that although Phenotip does not replace expert foetal care providers, it may provide support to sonographers, obstetricians, geneticists and foetal medicine specialists, to reach a diagnosis of a syndrome antenatally.
Read the open access article
Go to the Phenotip website

Rare Disease Biobanks are invited to publish their collection the RD-Connect Catalogue

Access to high-quality biological materials is essential for research on rare diseases. The new RD-Connect Catalogue of rare disease biological samples aims to unite rare biomaterials by facilitating sample search, and creating a strong network of rare disease biobanks in Europe. The sample catalogue, together with patient databases and clinical bioinformatics, is one of the three essential assets of the RD-Connect integrated platform.

Many benefits that bring a positive impact on the operations of the rare disease biobanks are available when they participate such as greater visibility in a global setting facilitating new collaborations as well as the ability to maximise the impact of their biobank. Participants will also have access to training material and policies according to international standards. Additionally interoperability in an international setting will also be assured by RD-Connect.

Existing European rare disease biobank networks such as EuroBioBank and TNGB (Telethon Network of Genetic Biobanks) are associated partners of RD-Connect, where they have contributed the establishment of data models and workflows. In addition, means to standardize biosample and data sharing procedures on ethical and legal grounds has been carefully considered within RD-Connect with dialogues from patient associations and international bodies. Biobanks that participate in the RD-Connect catalogue will become a part of a dynamic community that seeks to bring advancements in rare disease research.

How rare disease biobanks can contribute to the sample catalogue
In order to ensure the high quality of biological samples in research, all biobanks wishing to list biosamples via RD-Connect will be subjected to a simple assessment process before formal acceptance to the RD-Connect Catalogue and platform. The entire process is explained in detail on their webpage. Biobanks will receive feedback within two months of submission on the outcome of the review.

Once accepted onto the RD-Connect catalogue, the biobank will have access to the catalogue database, where its own basic information can be inserted or curated. The biobank will at this point on be visible and be listed as one of the contributing RD-Connect biobanks. During the next phase the biobanks will submit the minimal dataset on their sample collection to the platform, and begin sharing samples via the RD-Connect catalogue.

Using Registries to Recruit Subjects for Clinical Trials
A study published in Contemporary Clinical Trials studied the use of patient/disease registries to recruit potential subjects for prospective clinical trials - describing the number, types and major benefits of using this approach. After conducting a focused database search in PubMed, EMBASE, and Web of Science for studies that used registries to recruit subjects for clinical trials published between the years 2004-2014, the authors found that registries are used very often to “identify very large number of subjects for screening for eligibility for clinical trials, especially in very large trials, rare disease trials, and trials involving minority patients”. The authors believe that with the help of registries potential subjects can be efficiently screened for eligibility and enrollment in prospective clinical trials, which can be a timely recruitment strategy.
Read the PubMed abstract

Validity of participant-reported diagnoses in an online patient registry
With increased internet accessibility worldwide, it is now possible to assemble individuals with rare diseases through web-based patient registries. However, the validity of participant reported medical diagnoses is unknown. A study published in Contemporary Clinical Trials evaluated the accuracy of participant-reported Neurofibromatosis Type 1 (NF1) diagnoses among participants in the NF1 Patient Registry Initiative. The authors obtained medical records for participants and classified them as having definite, probable, suspected, or no NF1 diagnosis. After a thorough analysis, the authors concluded that individuals enrolling in the NPRI accurately report their NF1 diagnosis and that medical record verification is matches with participant-reported information to a great extent.
Read the PubMed abstract


Ethical, Legal & Social Issues
How much can patients be involved in descions towards reducing uncertainities around orphan drugs?
An article published in Patient performed a systematic review to identify existing and proposed opportunities for patients with rare diseases and their families to provide input aimed at reducing decision uncertainties throughout the lifecycle of an orphan drug. The authors found several roles for rare disease patients in this context, although it was mostly restricted to addressing the clinical benefit of the drug in question. According to the authors, opportunities to be involved in discussions related to “‘value for money’, affordability, and adoption/diffusion are limited”.
Read the PubMed abstract


Orphanet News
Now Online Diagnostic Criteria for diseases
Information on diagnostic criteria for rare diseases which completes the clinical signs is now published in the 'Detailed information section' at the bottom of the disease page on the Orphanet website. This information is provided so as to avoid serial misdiagnosis and facilitate early therapeutic management. They are extracted from peer-reviewed articles and validated by the international community. Information is given with indication regarding their interpretation. The Diagnostic criteria for the following diseases can be found on the disease page:
Marfan syndrome
Autoimmune lymphoproliferative syndrome
Pudendal neuralgia
Proteus syndrome
Hereditary nonpolyposis colon cancer
IgG4-related sclerosing disease
Rett syndrome
Gorlin syndrome
PTEN hamartoma tumor syndrome
Homozygous familial hypercholesterolaemia
Nakajo-Nishimura syndrome


New Syndromes

Familial inflammatory syndrome with lupus-like manifestations due to germline dominant gain-of-function mutations in TMEM173
The authors evaluated a non-consanguineous family of mixed European descent, with 4 members affected by systemic inflammatory and autoimmune conditions, including lupus, with variable clinical expression. They identified a germline dominant gain-of-function mutation in TMEM173.
Consult the Pubmed abstract

J Clin Invest. ; 124(12):5516-20 ; December 2014
Novel 3p14.1p13 microdeletion syndrome with distal limb contractures and severe developmental delay in four patients
The authors reported on four patients with syndromic distal limb contractures presenting with a de novo 3p14.1p13 microdeletion. The clinical features associated multiple contractures, feeding problems, developmental delay, and intellectual disability. Facial dysmorphism was constant with low-set posteriorly rotated ears and blepharophimosis.
Consult the Pubmed abstract

Am J Med Genet A. ; 164A(12):3027-34 ; December 2014
3p25.3 microdeletions of SLC6A1 and SLC6A11 could result in intellectual disability, epilepsy, ataxia and stereotypic hand movements in three patients
The authors reported on three novel patients with overlapping proximal 3p25.3 microdeletions showing a consistent non-3p-phenotype with intellectual disability, epilepsy or electroencephalography abnormalities, ataxia and stereotypic hand movements. SLC6A1 and SLC6A11 were considered as suitable candidates for the major clinical features of the patients.
Consult the Pubmed abstract

Am J Med Genet A. ; 164A(12):3061-8 ; December 2014
Diabetes mellitus and multisystemic neurodegeneration caused by loss-of-function mutations in DNAJC3
The authors investigated three siblings with juvenile-onset diabetes and central and peripheral neurodegeneration, including ataxia, upper-motor-neuron damage, peripheral neuropathy, hearing loss, and cerebral atrophy. Exome sequencing identified a homozygous stop mutation in DNAJC3. Screening of a diabetes database with 226,194 individuals yielded eight phenotypically similar individuals and one family carrying a homozygous DNAJC3 deletion.
Consult the Pubmed abstract

Am J Hum Genet. ; 95(6):689-97 ; December 2014
Novel lethal congenital contracture syndrome (LCCS6) caused by a homozygous variant in ZBTB42 in a consanguineous Saudi family
The authors identified a novel homozygous variant in ZBTB42 in a consanguineous Saudi family with multiple stillbirths presenting with a new lethal congenital contracture syndrome termed LCCS6.
Consult the Pubmed abstract

Hum Mol Genet. ; 23(24):6584-93 ; December 2014
Ovarian failure, short stature, and chromosomal instability associated with MCM9 mutations in two unrelated consanguineous Turkish families
The authors studied two unrelated consanguineous Turkish families with daughters exhibiting primary amenorrhea, short stature, and a 46,XX karyotype. Homozygous pathogenic variants in MCM9 were identified.
Consult the Pubmed abstract

Am J Hum Genet. ; 95(6):754-62 ; December 2014

New Genes

MERRF is associated with a homozygous splice-site mutation in CARS2 in a consanguineous family with 2 affected individuals
Consult the Pubmed abstract
To read more about "MERRF"

Neurology ; 83(23):2183-7 ; December 2014
Isolated retinal degeneration and Bardet-Biedl syndrome caused by IFT172 mutations in three families
Consult the Pubmed abstract
To read more about "Bardet-Biedl syndrome"
To read more about "Retinal dystrophy"

Hum Mol Genet. ; 24(1):230-42 ; January, 2015
Overgrowth, macrocephaly and facial dysmorphism due to mutations in RNF125 in six patients from four families
Consult the Pubmed abstract
To read more about "Overgrowth - macrocephaly - facial dysmorphism"

Hum Mutat. ; 35(12):1436-41 ; December 2014
Gigantism and acromegaly are linked to GPR101 mutation
Consult the Pubmed abstract
N Engl J Med. ; 371(25):2363-74 ; December 2014
Autosomal recessive non-syndromic intellectual disability caused by biallelic truncating mutations in FMN2 in two consanguineous families
Consult the Pubmed abstract
To read more about "Autosomal recessive non-syndromic intellectual disability"

Am J Hum Genet. ; 95(6):721-8 ; December 2014
Catel-Manzke syndrome due to homozygous and compound-heterozygous mutations in TGDS in seven unrelated individuals
Consult the Pubmed abstract
To read more about "Catel-Manzke syndrome"

Am J Hum Genet. ; 95(6):763-70 ; December 2014
Early-onset parkinsonism and intellectual disability caused by mutations in RAB39B
Consult the Pubmed abstract
To read more about "Early-onset parkinsonism - intellectual disability"

Am J Hum Genet. ; 95(6):729-35 ; December 2014
Choanal atresia-deafness-cardiac defects-dysmorphism syndrome due to loss-of-function mutations in TXNL4A in 9 families
Consult the Pubmed abstract
To read more about "Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome"

Am J Hum Genet. ; 95(6):698-707 ; December 2014
Mesoaxial synostotic syndactyly with phalangeal reduction linked to BHLHA9 mutations in six families
Consult the Pubmed abstract
To read more about "Mesoaxial synostotic syndactyly with phalangeal reduction"

Am J Hum Genet. ; 95(6):649-59 ; December 2014
Galloway-Mowat syndrome due to loss-of-function mutations in WDR73 in two unrelated families
Consult the Pubmed abstract
To read more about "Galloway-Mowat syndrome"

Am J Hum Genet. ; 95(6):637-48 ; December 2014
Leigh syndrome is associated with mutations in GTPBP3 in 11 individuals from 9 families
Consult the Pubmed abstract
To read more about "Leigh syndrome"

Am J Hum Genet. ; 95(6):708-20 ; December 2014
Familial thoracic aortic aneurysm and aortic dissection linked to MFAP5 loss-of-function mutations
Consult the Pubmed abstract
To read more about "Familial thoracic aortic aneurysm and aortic dissection"

Am J Hum Genet. ; 95(6):736-43 ; December 2014
Infantile myofibromatosis: novel homozygous variant in NDRG4 in two brothers
Consult the Pubmed abstract
To read more about "Infantile myofibromatosis"

Eur J Med Genet. ; 57(11-12):643-8 ; November 2014
Malignant Sertoli-Leydig cell tumor of ovary and well-differentiated fetal adenocarcinoma of the lung linked to DICER1 in one patient
Consult the Pubmed abstract
To read more about "Malignant Sertoli-Leydig cell tumor of ovary"
To read more about "Well-differentiated fetal adenocarcinoma of the lung"

Eur J Med Genet. ; 57(11-12):621-625 ; October 2014
Macrocephaly-autism syndrome is associated with CHD8 mutation
Consult the Pubmed abstract
To read more about "Macrocephaly-autism syndrome"

Am J Med Genet A. ; 164A(12):3137-41 ; December 2014
Persistent hyperplastic primary vitreous and Norrie disease linked to a novel mutation in TSPAN12
Consult the Pubmed abstract
To read more about "Persistent hyperplastic primary vitreous"
To read more about "Norrie disease"

Am J Med Genet A. ; 164A(12):2996-3002 ; December 2014
Autosomal dominant palmoplantar keratoderma and congenital alopecia linked to GJA1 mutation
Consult the Pubmed abstract
To read more about "Autosomal dominant palmoplantar keratoderma and congenital alopecia"

Hum Mol Genet. ; 24(1):243-50 ; January, 2015
Perrault syndrome due to compound heterozygous mutations in C10orf2 in two families
Consult the Pubmed abstract
To read more about "Perrault syndrome"

Neurology ; 83(22):2054-61 ; November 2014
Complex cerebral malformations due to mutations in KATNB1
Consult the Pubmed abstract
Neuron ; 84(6):1226-39 ; December 2014
Common variable immunodeficiency linked to CTLA4 mutations
Consult the Pubmed abstract
To read more about "Common variable immunodeficiency"

Nat Med. ; 20(12):1410-6 ; December 2014
Tetralogy of Fallot could be linked to TBX5 heterozygous mutations
Consult the Pubmed abstract
To read more about "Tetralogy of Fallot"

Am J Med Genet A. ; 164A(12):3100-7 ; December 2014
Intellectual disability: mosaic deletion of EXOC6B might play an important role
Consult the Pubmed abstract
Am J Med Genet A. ; 164A(12):3088-94 ; December 2014
Systemic sclerosis: identification of IL12RB1 as a novel susceptibility locus
Consult the Pubmed abstract
To read more about "Systemic sclerosis"

Arthritis Rheumatol. ; 66(12):3521-3 ; December 2014
Involvement of CNTNAP3 gene in the development of testicular germ cell tumor
Consult the Pubmed abstract
To read more about "Germ cell tumor of testis"

Orphanet J Rare Dis. ; 9(1):181 ; November 2014
Fibrolamellar hepatocellular carcinoma: translocation between CLPTM1L and GLIS3 promotes cancer phenotypes in hepatocellular carcinoma cell lines
Consult the Pubmed abstract
To read more about "Fibrolamellar hepatocellular carcinoma"

Hum Mol Genet. ; 24(1):50-63 ; January, 2015
Multiple system atrophy: LRRK2 exonic variants may contribute to susceptibility
Consult the Pubmed abstract
To read more about "Multiple system atrophy"

Neurology ; 83(24):2256-61 ; December 2014
Autosomal recessive cerebellar ataxia may be caused by CWF19L1 homozygous splice mutations
Consult the Pubmed abstract
To read more about "Autosomal recessive cerebellar ataxia"

Neurology ; 83(23):2175-82 ; December 2014

Research in Action

Clinical Research
Marfan syndrome: no significant difference in the rate of aortic-root dilatation between atenolol versus losartan treatment in children and young adults
Consult the Pubmed abstract Consult this study on Orphanet

To read more about "Marfan syndrome"

N Engl J Med. ; 371(22):2061-71 ; November 2014
Severe hemophilia B: long-term safety and efficacy of factor IX gene therapy
Consult the Pubmed abstract

To read more about "Severe hemophilia B"

N Engl J Med. ; 371(21):1994-2004 ; November 2014
Subependymal giant cell astrocytoma in patients with tuberous sclerosis: reduction or stabilization of tumor volume with everolimus
Consult the Pubmed abstract

To read more about "Subependymal giant cell astrocytoma"
To read more about "Tuberous sclerosis"

Lancet Oncol. ; 15(13):1513-20 ; December 2014
Huntington disease: safety, tolerability and efficacy of PBT2, a metal protein-attenuating compound
Consult the Pubmed abstract

To read more about "Huntington disease"

Lancet Neurol. ; 14(1):39-47 ; January, 2015
Inclusion body myositis: bimagrumab increases thigh muscle volume at 8 weeks
Consult the Pubmed abstract

To read more about "Inclusion body myositis"

Neurology ; 83(24):2239-46 ; December 2014
West syndrome: minimizing vigabatrin treatment to 6 months will reduce the prevalence of vigabatrin retinal damage
Consult the Pubmed abstract
To read more about "West syndrome"

Neurology ; 83(24):2262-8 ; December 2014
Hyperlipoproteinemia type 1: ISIS 304801, an inhibitor of APOC3 messenger RNA, reduces plasma APOC3 levels and triglyceride levels
Consult the Pubmed abstract
To read more about "Hyperlipoproteinemia type 1"

N Engl J Med. ; 371(23):2200-6 ; December 2014
Fabry disease: agalsidase alfa is well tolerated and demonstrates a stabilizing clinical effect in pediatric patients
Consult the Pubmed abstract
To read more about "Fabry disease"

Orphanet J Rare Dis. ; 26;9(1):169 ; November 2014
Graft versus host disease: the addition of mycophenolate mofetil to steroids did not improve clinical outcome over steroids alone
Consult the Pubmed abstract
To read more about "Graft versus host disease"

Blood ; 124(22):3221-7 ; November 2014
Isolated hypospadias: possible preventive effect of high doses of folic acid
Consult the Pubmed abstract
Am J Med Genet A. ; 164A(12):3108-14 ; December 2014
First report of allopregnanolone use to treat and resolve status epilepticus in children
Consult the Pubmed abstract
Ann Neurol. ; 76(6):911-5 ; December 2014
Adult pulmonary Langerhans cell histiocytosis: cladribine may be effective therapy in patients with progressive disease
Consult the Pubmed abstract
To read more about "Adult pulmonary Langerhans cell histiocytosis"

Orphanet J Rare Dis. ; 9(1):191 ; November 2014
Acquired thrombotic thrombocytopenic purpura: ADAMTS13 activity evaluation and anti-ADAMTS13 antibody detection could help to predict the risk of complications in pregnant women
Consult the Pubmed abstract
To read more about "Acquired thrombotic thrombocytopenic purpura"

Orphanet J Rare Dis. ; 9(1):193 ; November 2014
Acromegaly: treatment with somatostatin analogs can restore immature endothelial progenitor cells to normal levels
Consult the Pubmed abstract
To read more about "Acromegaly"

J Clin Endocrinol Metab. ; 99(12):E2549-56 ; December 2014
Glycogen storage disease due to glycogen debranching enzyme deficiency: improved energetic state of heart and skeletal muscle by introduction of Atkins diet
Consult the Pubmed abstract
To read more about "Glycogen storage disease due to glycogen debranching enzyme deficiency"

Orphanet J Rare Dis. ; 9(1):196 ; November 2014
Down syndrome: early thyroxine treatment of children only benefits growth
Consult the Pubmed abstract
To read more about "Down syndrome"

J Clin Endocrinol Metab. ; 99(12):E2722-9 ; December 2014
Neonatal diabetes mellitus: sulfonylurea therapy appears to be safe and often successful before genetic testing results are available
Consult the Pubmed abstract
To read more about "Neonatal diabetes mellitus"

J Clin Endocrinol Metab. ; 99(12):E2709-14 ; December 2014
Therapeutic Approaches

Mucopolysaccharidosis type 1: intrathecal gene therapy corrects central nervous system pathology in a feline model
Consult the Pubmed abstract
To read more about "Mucopolysaccharidosis type 1"

Mol Ther. ; 22(12):2018-27 ; December 2014
Hurler syndrome: normalization and improvement of central nervous system deficits in mice models after long-term peripheral delivery of BBB-targeted iduronidase
Consult the Pubmed abstract
To read more about "Hurler syndrome"

Mol Ther. ; 22(12):2028-37 ; December 2014
Friedreich ataxia: dyclonine rescues frataxin deficiency in mouse models and buccal cells of patients
Consult the Pubmed abstract
To read more about "Friedreich ataxia"

Hum Mol Genet. ; 23(25):6848-62 ; December 2014
Charcot-Marie-Tooth disease type 1A: PXT3003 downregulates Pmp22 over-expression and improves myelination, axonal and functional parameters in cellular and rat models
Consult the Pubmed abstract
To read more about "Charcot-Marie-Tooth disease type 1A"

Orphanet J Rare Dis. ; 9(1):201 ; December 2014
Cystic fibrosis: cysteamine (LYNOVEX), a novel mucoactive antimicrobial and antibiofilm agent, provides potential for a new therapeutic strategy
Consult the Pubmed abstract
To read more about "Cystic fibrosis"

Orphanet J Rare Dis. ; 9(1):189 ; November 2014
Dystrophic epidermolysis bullosa: genetically repaired induced pluripotent stem cells-derived fibroblasts restored the mechanical resistance to skin blistering in mice
Consult the Pubmed abstract
To read more about "Dystrophic epidermolysis bullosa"

Sci Transl Med. ; 6(264):264ra165 ; November 2014
Hantavirus pulmonary syndrome: DNA vaccine–derived human immunoglobulins produced in transchromosomal bovines protect in lethal models
Consult the Pubmed abstract
To read more about "Hantavirus pulmonary syndrome"

Sci Transl Med. ; 6(264):264ra162 ; November 2014
K27M-expressing pediatric brainstem glioma: increasing H3K27 methylation by inhibiting K27 demethylase is a valid therapeutic strategy
Consult the Pubmed abstract
Nat Med. ; 20(12):1394-6 ; December 2014
Diffuse intrinsinc pontine glioma: inhibition of JMJD3 has robust antitumor activity in xenografts
Consult the Pubmed abstract
Nat Med. ; 20(12):1378-9 ; December 2014
Oral delivery of ACE2/Ang-(1–7) bioencapsulated in plant cells protects against experimental uveitis
Consult the Pubmed abstract
To read more about "Uveitis"

Mol Ther. ; 22(12):2069-82 ; December 2014
Diagnostic Approaches

Sézary syndrome: CD158k is a reliable marker for the diagnosis of the disease
Consult the Pubmed abstract
To read more about "Sézary syndrome"

J Invest Dermatol. ; 135(1):247-57 ; January, 2015
IgG4-related diseases: poor specificity and low positive predictive value for serum IgG4 concentrations as a diagnostic tool
Consult the Pubmed abstract
To read more about "Autoimmune pancreatitis type 1"
To read more about "Immunoglobulin G4-related sclerosing disease"
To read more about "Mikulicz disease"

Ann Rheum Dis. ; 74(1):14-8 ; January, 2015
Niemann-Pick disease type C: the suspicion index emphasizes the importance of a multisystem evaluation, but seems to be weak in monosymptomatic and infantile patients
Consult the Pubmed abstract
To read more about "Niemann-Pick disease type C"

Orphanet J Rare Dis. ; 9(1):176 ; November 2014
Progressive multifocal leukoencephalopathy: anti-JC virus antibody levels in serum or plasma, and cerebrospinal fluid JC virus antibody index as diagnostic tools
Consult the Pubmed abstracts
To read more about "Progressive multifocal leukoencephalopathy"

Ann Neurol. ; 76(6):792-801, 802-12 ; December 2014
Beta-propeller protein-associated neurodegeneration: early magnetic resonance imaging can help diagnosing the disease in childhood
Consult the Pubmed abstract
To read more about "Beta-propeller protein-associated neurodegeneration"

Am J Med Genet A. ; 164A(12):3095-9 ; December 2014

Patient Management and Therapy
Medullary thyroid carcinoma: review on the treatment
Consult the Pubmed abstract

To read more about "Medullary thyroid carcinoma"

J Clin Endocrinol Metab. ; 99(12):4390-6 ; December 2014
Primary biliary cirrhosis: review on obeticholic acid for the treatment
Consult the abstract

To read more about "Primary biliary cirrhosis"

Expert Opinion on Orphan Drugs ; 2(12):1351-1358 ; December 2014
Papillary or follicular thyroid carcinoma: review on lenvatinib for the treatment
Consult the abstract

To read more about "Differentiated thyroid carcinoma"

Expert Opinion on Orphan Drugs ; 2(12):1331-1340 ; December 2014
Pediatric homozygous familial hypercholesterolemia: review on rosuvastatin for the treatment
Consult the abstract

To read more about "Homozygous familial hypercholesterolemia"

Expert Opinion on Orphan Drugs ; 2(12):1325-1330 ; December 2014
Pulmonary arterial hypertension: review on beraprost sodium MR for the treatment
Consult the abstract

To read more about "Pulmonary arterial hypertension"

Expert Opinion on Orphan Drugs ; 2(12):1315-1323 ; December 2014
Inclusion body myositis: review on treatment strategies
Consult the abstract

To read more about "Inclusion body myositis"

Expert Opinion on Orphan Drugs ; 2(12):1255-1265 ; December 2014
Biliary atresia: review on treatment outcomes
Consult the abstract

To read more about "Biliary atresia"

Expert Opinion on Orphan Drugs ; 2(12):1267-1277 ; December 2014
Hemophilia: review on optimal therapy for inhibitors
Consult the Pubmed abstract
To read more about "Hemophilia"

Blood ; 124(23):3365-3372 ; November 2014
Hodgkin lymphoma, classical and anaplastic large cell lymphoma: review on brentuximab vedotin treatment
Consult the Pubmed abstract
To read more about "Classic Hodgkin lymphoma"
To read more about "Anaplastic large cell lymphoma"

Blood ; 124(22):3197-200 ; November 2014
Glioblastoma: a review on orphan drugs
Consult the abstract
To read more about "Glioblastoma"

Orphan Drugs : Research and Reviews ; Volume 2014:4 Pages 83—91 ; November 2014
Glycogen storage disease due to muscle glycogen phosphorylase deficiency: review on pharmacological and nutritional treatment
Consult the Pubmed abstract
To read more about "Glycogen storage disease due to muscle glycogen phosphorylase deficiency"

Cochrane Database Syst Rev. ; 11:CD003458 ; November 2014
Thoracic outlet syndrome: review on treatment
Consult the Pubmed abstract
To read more about "Thoracic outlet syndrome"

Cochrane Database Syst Rev. ; 11:CD007218 ; November 2014
Spina bifida: review on prenatal versus postnatal repair procedures
Consult the Pubmed abstract
Cochrane Database Syst Rev. ; 10:CD008825 ; October 2014
Friedreich ataxia and other hereditary ataxia syndromes: review on treatment for speech disorder
Consult the Pubmed abstract
To read more about "Friedreich ataxia"

Cochrane Database Syst Rev. ; 10:CD008953 ; October 2014
Myasthenia gravis: review on acetylcholinesterase inhibitor treatment
Consult the Pubmed abstract
To read more about "Myasthenia gravis"

Cochrane Database Syst Rev. ; 10:CD006986 ; October 2014
Interstitial lung disease: review on pulmonary rehabilitation
Consult the Pubmed abstract
To read more about "Interstitial lung disease"

Cochrane Database Syst Rev. ; 10:CD006322 ; October 2014
Paroxysmal nocturnal hemoglobinuria: review on eculizumab for the treatment
Consult the Pubmed abstract
To read more about "Paroxysmal nocturnal hemoglobinuria"

Cochrane Database Syst Rev. ; 10:CD010340 ; October 2014
Infant acute respiratory distress syndrome: review on ambroxol treatment for woment at risk of preterm birth
Consult the Pubmed abstract
To read more about "Infant acute respiratory distress syndrome"

Cochrane Database Syst Rev. ; 10:CD009708 ; October 2014
Sickle cell anemia: review on prophylactic antibiotics for preventing pneumococcal infection in children
Consult the Pubmed abstract
To read more about "Sickle cell anemia"

Cochrane Database Syst Rev. ; 11:CD003427 ; November 2014
Cystic fibrosis: reviews on molecular understanding, clinical application, and treatment
Consult the Pubmed abstracts
To read more about "Cystic fibrosis"

Nat Rev Genet. ; 16(1):45-56 ; January, 2015Cochrane Database Syst Rev. ; 10:CD009876, 10:CD001915, 11:CD000406, 10:CD008227 ; October 2014
Cochrane Database Syst Rev. ; 11:CD004197, 11:CD001912 ; November 2014
Hodgkin lymphoma: review on survivorship recommendations
Consult the Pubmed abstract
To read more about "Hodgkin lymphoma"

Blood ; 124(23):3373-3379 ; November 2014
Tetralogy of Fallot: prospective follow-up of 40 years after surgical correction
Consult the Pubmed abstract
To read more about "Tetralogy of Fallot"

Circulation ; 130(22):1944-53 ; November 2014
Methylmalonic acidemia with homocystinuria, type cblC: a review
Consult the Pubmed abstract
To read more about "Methylmalonic acidemia with homocystinuria, type cblC"

Orphanet J Rare Dis. ; 9(1):161 ; November 2014
Chronic immune thrombocytopenic purpura in children: review on clinical and laboratory predictors
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood ; 124(22):3295-307 ; November 2014
Dermatomyositis and polymyositis: review on optimal management of interstitial lung disease
Consult the abstract
To read more about "Dermatomyositis"
To read more about "Polymyositis"

Orphan Drugs : Research and Reviews ; Volume 2014:4 Pages 93-107 ; November 2014
Pediatric stroke: two reviews on management, follow-up, pressing issues and promising directions
Consult the Pubmed abstracts
Arch Pediatr. ; 21(12):1305-15 ; December 2014
Lancet Neurol. ; 14(1):92-102 ; January, 2015
Trisomy 13: review on medical conditions of nine children over the age of one year
Consult the Pubmed abstract
To read more about "Trisomy 13"

Am J Med Genet A. ; 164A(12):2987-95 ; December 2014
CHARGE syndrome: review on cognitive-motor profile, clinical characteristics and diagnosis
Consult the Pubmed abstract
To read more about "CHARGE syndrome"

Am J Med Genet A. ; 164A(12):3042-51 ; December 2014
Eosinophilic esophagitis: review on advances on clinical management
Consult the Pubmed abstract
To read more about "Eosinophilic esophagitis"

Gastroenterology ; 147(6):1238-1254 ; August 2014
Acroosteolysis dominant type: a review
Consult the Pubmed abstract
To read more about "Acroosteolysis dominant type"

Orphanet J Rare Dis. ; 9(1):200 ; December 2014
Bullous pemphigoid in infants: review on characteristics, diagnosis and treatment
Consult the Pubmed abstract
To read more about "Bullous pemphigoid"

Orphanet J Rare Dis. ; 9(1):185 ; December 2014
Inborn errors of metabolism presenting as cerebral palsy mimics: systematic literature review
Consult the Pubmed abstract
To read more about "Rare inborn errors of metabolism"

Orphanet J Rare Dis. ; 9(1):197 ; November 2014
Cerebrotendinous xanthomatosis: review of pathogenesis, clinical manifestations, diagnosis and management
Consult the Pubmed abstract
To read more about "Cerebrotendinous xanthomatosis"

Orphanet J Rare Dis. ; 9(1):179 ; November 2014
A Nature review supplement on hemophilia
Consult the supplement
To read more about "Hemophilia"

Nature ; 515:S157-S173 ; November 2014
Coffin-Siris syndrome: special issue of the American Journal of Medical Genetics
Consult the supplement
To read more about "Coffin-Siris syndrome"

American Journal of Medical Genetics. ; 166(3):241-366 ; September 2014
Three new and seventeen updated GeneReviews published
GeneReviews are expert-authored, peer-reviewed disease descriptions ("chapters") presented in a standardized format and focused on clinically relevant and medically actionable information on the diagnosis, management, and genetic counseling of patients and families with specific inherited conditions. Three new GeneReviews have been published for:
ADCY5-related dyskinesia
Duarte variant galactosemia
Susceptibility to infection-induced acute encephalopathy 3

Seventeen updated GeneReviews have been published for:
Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia
Charcot-Marie-Tooth disease type 1
Familial dysautonomia
POLG-related disorders
Pallister-Hall syndrome
Hermansky-Pudlak syndrome
Huntington disease
LRRK2-related Parkinson disease
Spastic paraplegia 3A
Central core disease
Unverricht-Lundborg disease
Chondrodysplasia punctata 1, X-linked
Jervell and Lange-Nielsen syndrome
Renal coloboma syndrome
Thiamine-responsive megaloblastic anemia syndrome


Orphan Drugs
Drug repurposing based on a new concept: Homopharma
Drug repurposing is increasingly being recognised as an important pathways in order to bring treatments for rare diseases quicker to the patients. New tools are being designed to discover new targets for medications that already have marketing authorisation, one of which is described in the Orphanet Journal of Rare Diseases called “Homopharma”. This concept is based on the fact that a set of proteins which have the conserved binding environment can be matched with a set of compounds are often able to inhibit these proteins. According to the authors this method can identify potential targets of compounds and reveal key binding environment and thus be instrumental in for discovering new usages for existing drugs. The experimental work of the authors showed that the four flavonoid derivatives, which can be used as anticancer compounds, selected by the authors, was able to inhibit multiple protein-kinases with similar physiochemical properties efficiently. The authors believe that “the Homopharma concept can have the potential for understanding molecular binding mechanisms and providing new clues for drug development”.
Read the open access article

Regulatory News
Orphan medicinal product regulations in EU and US
A paper published in Regulatory Toxicology and Pharmacology presents an analysis of the basic similarities and differences between the rules and regulations put forth by regulatory agencies of US and EU for development of medicinal products for rare diseases, also called orphan medicinal products. After describing the Orphan Drug Act (ODA) which was passed by the US FDA in 1983 and the Orphan Drug Regulation EC/141/2000 – EU enacted by the European Union in 1999, the authors compared the major perpectives that these acts have brought forth. According to the author, ODA not only encompasses drugs and devices, it also provides for greater flexibility which is not observed in the EU regulation. However, the author believes that considerable changes are taking place at the European level such as the adoption of national plans for rare diseases in many European countries which will prove to be beneficial to sponsors. Additionally, the author also outlines the joint initiatives of EMA and FDA concerning the procedures involving orphan drug designation which will also speed the process for the sponsors to bring the orphan medicinal products into the two regions simultaneously. Finally, the author states that ‘the impact of the orphan drug rules and regulations has been tremendous and as a result of these there are many medicines available in market for rare diseases” but also recognises the importance of several other reforms that need to take place in order to bring orphan medicinal products into the market in a timely manner.
Read the PubMed abstract

Stem cell therapy recommended for conditional marketing approval in EU
Holoclar is the first stem cell therapy to be recommended by the European Medicines Agency (EMA) for approval in the European Union (EU). This advanced therapy medicinal product (ATMP) containing stem cells is the first medicine developed to treat moderate to severe limbal stem cell deficiency (LSCD) due to physical or chemical burns to the eye(s) in adults, a rare eye condition that can result in blindness. Holoclar is based on autologous cultures of limbal stem cells, where a small sample of remaining stem cells in patients with LSCD are taken and grown into larger numbers in the laboratory and placed back on to the surface of the eye. Based on a robust assessment carried out by the Committee for Advanced Therapies (CAT) and the Agency’s expert committee for ATMPs, the Committee for Medicinal Products for Human Use (CHMP) recommended a conditional marketing authorisation of Holoclar in the EU. According to the EMA, “although the data supplied by the applicant show that the medicine's benefits outweigh its risks, the data are based on retrospective studies and are not yet comprehensive (and) therefore, an additional study on the use of Holoclar should be conducted”.
For further information go to the EMA website

Political and Scientific News
Clinical trial designs for rare diseases: International Rare Cancers Initiative portfolio

The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. European Journal of Cancer has published the methods used in ICRI portfolio which was presented in the multi-disciplinary workshop held in Amsterdam in September 2013 as well as other methods that have not yet been realised. The article explains that clinical trials can be designed using a wide array of possibilities as there is no ‘one size fits all’ solution, due to the challenges faced while studying rare cancers. Notable approaches to conducting clinical trials for rare cancers within the constraints of sample size and insufficient background information, common to rare cancers, are exemplified in this article. Other unrealised trial designs are also discussed, providing the readers and overview of the different types of clinical trials that are possible to combat the challenges of bringing treatments for rare cancers to the fore. The article notes that “progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases”, therefore warranting the use of non-traditional methods for conducting trials.
Read the open access article



Research on Eosinophil Associated Disorders (R01) and (R21)
These two NIH grants are open to non-US entities. Areas of interest include, but are not limited to, the following topics
Research on the fundamental immuno-biologic and mechanistic roles of human eosinophils in Eosinophil-Associated Disorders
Development of predictive biomarkers and clinical outcomes for Eosinophil-Associated Disorders Development of novel therapeutic targets for use in Eosinophil-Associated Disorders
Preclinical evaluation of existing therapeutic agents for use in Eosinophil-Associated Disorders
Identification and improvement of novel invasive and non-invasive techniques for the diagnosis andclinical monitoring of Eosinophil-Associated Disorders
Improvement of diagnostic criteria that delineate differential phenotypes within Eosinophil-Associated Disorders
Development of novel animal models with improved predictive value for human Eosinophilic-Associated Disorders
Earliest Submission Date for the R01 grant: 5 January 2015
Earliest Submission Date for the R21 grant: 16 January 2015

For further details on the R01 grant
For further details on the R21 grant

Support for European Reference Networks: efficient network modelling and validation (Horizon 2020, European Commission)
This is a call for proposals that will provide coordinated support to the activities of the ERN under the framework of Article 12 of Directive 2011/24/EU concerning implementation of a validated system methodology for the optimal organisation, governance, maintenance and continuous monitoring and evaluation of ERN and their centers. A budget of €29,000,000 has been made available for successful proposals in this area.Each proposal should present quantitative or qualitative indicators to quantify the potential impact.
Application Deadline: 21 April, 2015
For Further Information

ERare : Joint Transnational Call 2015 Preannouncement
ERare has opened the seventh ERare joint call for funding multilateral research projects on rare diseases (JTC 2015) together with the European Commission (EC) under the ERANetcofund mechanism. The call is expected to be opened simultaneously by the parties in their respective countries.The following 17 countries (23 funding agencies) intend toparticipate in this call: Austria, Belgium (Flanders and French speaking community), Canada (including Québec), France, Germany, Greece, Hungary, Israel, Italy, Latvia, Poland,Portugal, Romania, Spain, Switzerland, The Netherlands and Turkey.
The aim of the call is to enable scientists in different countries to build an effectivecollaboration on a common interdisciplinary research project based on complementarities andsharing of expertise, with a clear translational research approach.Projects shall involve a group of rare diseases or a single rare disease following theEuropean definition. For more information, details of the topic, eligibility criteria andtimeline go to www.erare.eu

DEBRA International research grants
The spring 2015 call for applications for new research funding from DEBRA International is now open, with a submission deadline of 1 March 2015. EpidermolysisBullosa (EB) is a group of rare genetic skin conditions, characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. This grant aims to:
  • Improve the understanding of the biology and genetics of all forms of EB, as better understanding can lead to new approaches to diagnose and treat EB;
  • Work towards the development of therapies (including possible gene-therapies, cell-therapies, drug therapies or protein therapies);
  • Understand the nature of wound healing and the development of skin cancer in EB, and seek to develop better treatments and prevention strategies;
  • Support clinical care research to improve the management of EB through symptom relief.

  • For Further Information

    Fondation Jerome Lejeune grant application
    Scientific Advisory Board of the Jérôme Lejeune Foundation invites submission from research projects aiming at deciphering the pathophysiology of the cognitive deficits of patients, especially those with trisomy 21 (Down syndrome) and other rare abnormalities such as fragile X, cri du chat, Rett, Williams-Beuren, Prader-Willi, Angelman, and other syndromes, excluding autism. - See more at: http://www.fondationlejeune.org/en/our-missions-and-actions/research/apply-for-a-grant-obtain-funding#sthash.vKIIZgmo.dpuf
    A call for European research projects on neurodegenerative diseases: risk and protective factors, longitudinal cohort approaches and advanced experimental models”
    With the aim of tackling the leading medical and societal challenges faced by our society, a JPND joint transnational co-funded call was launched on January 8th, 2015 in partnership with the European Commission under the ERA-NET Co-fund scheme. The call aims to establish a limited number of ambitious, innovative, multi-national and multi-disciplinary collaborative research projects that will add value to existing research in three JPND priority areas: • Longitudinal Cohort Approaches • Advanced Experimental Models • Risk and Protective Factors
    For Further Information


    Partnersearch, Job Opportunities
    Call for Interest: Endowed Chair for Health Services Research for rare diseases in children
    The Kindness for Kids Foundation is a non-profit organisation based in Munich, which is involved since its inception in 2003 for children with rare diseases. Under the proposed endowed professorship for health services research for rare diseases in childhood, the Foundation is looking for a suitable medical faculty as the location thereof. Objective of the Chair is to sustainably improve the quality of life of children with rare diseases.
    You can find the complete announcement hereIf interested, please submit a letter of intent initially by 31 December 2014, a necessary precondition for the further application. The application deadline is 28 February, 2015. Please contact Dr. Barske responsible for the promotion of research at Kindness for Kids, by phone (089 21 56 85 80) or by email (j.barske@kindness-for-kids.de).


    Courses & Educational Initiatives

    ESH-ENERCA Training course on haemoglobin disorders: laboratory diagnosis and clinical management
    Date: 23-24 January, 2015
    Venue: Barcelona, Spain

    The course will cover the following topics: Epidemiology in practice, Clinical aspects of thalassaemia, Trends in biological aspects of thalassaemia, Abnormal haemoglobins and Complications and treatments of thalassaemia and sickle cell disease.
    Participants are encouraged to submit clinical cases or abstracts for presentation and discussion during the meeting. Submit your detailed clinical case(s)online
    Deadline for clinical cases and abstracts: 24 November, 2014
    For Further Information

    INVITATION: How To Identify Rare Disease Patients Workshop – 30th January
    Date: 30 January, 2015
    Venue: London, UK

    This workshop will explore different methods for identifying patients in order to build communities and recruit for clinical research. Throughout the day, there will be short group discussion sessions where delegates will be able to share their own experiences and work together to apply the advice from the day to their own organisations. If you would like to attend, please email Flóra by Friday, 16th January 2015.
    For Further Information

    European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
    Date: 23 February – 3 March, 2015
    Venue: Nimes, France

    It is designed to provide advanced training in constitutional, haematological, and oncological cytogenetics to medical graduates, pharmacists, pathologists, biologists, health professionals and researchers, with an academic qualification.
    For Further Information

    Health care guidelines on rare diseases: Quality assessment
    Date: 23-24 February, 2015
    Venue: Rome, Italy

    This course is part of the capacity building activities of the project RARE-Bestpractices. These activities have been conceived to support the upcoming European Reference Networks and Centres of Expertise in the development of their capacity to produce and use health care guidelines, according to the criteria set up by the Commission Delegated Decision of the 10/3/2014 (2014/286/EU).
    For more information.

    Courses offered by Recordati Rare Diseases Foundation
    The Recordati Rare Diseases Foundation is offering five courses planned for next year. For Further Information, please contact Cecilia Kellquist, Coordinator and member of the board, ckellquist@rrd-foundation.org/www.rrd-foundation.org.
    Advanced metabolic course: Controversies in management
    Date: 11-13 March, 2015
    Venue: Manchester, UK

    in partnership with Willink Biochemical Genetics Unit, Manchester Centre for Genomic Medicine, Central Manchester University Hospitals NHS Foundation Trust.
    For Further Information

    The changing spectrum of IMD: surviving longer and growing old with IMDs
    Date: 21-23 May, 2015
    Venue: Washington DC, US

    Children’s Hospital of Pittsburgh, the Division of Medical Genetics and Children’s National, Department of Genetics and Metabolism.
    Registration deadline: 8th April

    Classification and diagnostic approach of IMD affecting the synthesis and remodelling of complex lipids
    Date: 24-26 June 2015
    Venue: Paris, France

    in partnership with the Pitié-Salpêtrière Hospital Pierre et Marie Curie University Paris VI; the Academic Medical Center, University of Amsterdam and the University Children’s Hospital of Zurich.
    Registration deadline: 13th May

    Genetic congenital heart diseases
    Date: 7-9 October 2015
    Venue: Rome, Italy

    in partnership with Bambino Gesù Children’s Hospital, Rome
    Registration deadline: 27th August

    Neurotransmitter focus course
    Date: 9-10 November 2015
    Venue: Venice, Italy

    in partnership with University Hospital for Child and Adolescent Medicine of Heidelberg and University Hospital of Padua. Registration deadline: 26th September

    3Gb-TEST course on NGS: Next-generation sequencing in a diagnostic setting
    Date: 20-23 April, 2015
    Venue: Prague, Czech Republic

    This 4-day course on Next Generation Sequencing in Prague - Czech Republic in the period of 20-23th April 2015 will focus on clinical diagnostics using exome/genome sequences, variant identification and analysis including afternoon practicals (limited places). The course will also include an evening symposium co-organised by Milan Macek; “Genotranslation: Interpretation of genome data in diagnostics”
    For Further Information

    Date: 1-5 June, 2015
    Venue: Barcelona, Spain

    ExPRESS 2015 is the name of the exciting new programme for the upcoming annual EURORDIS Summer School. ExPRESS, which stands for Expert Patients and Researchers EURORDIS Summer School, will gather for the first time both researchers and patient representatives who will be trained together. The trainers are from patient organisations, research institutes and the European Medicines Agency. The four-day training programme develops the capacity of patients' advocates to act as experts in regulatory processes and further their implication in medicines development and advocacy actions both at the national and European levels.
    For Further Information contact Nancy Hamilton
    Visit the EURORDIS website for more information.

    Phenomin: European Advanced School for Mouse Phenogenomics
    Date: 8-12 June, 2015
    Venue: Alsace, France

    PHENOMIN offers an international training of excellence providing master's degrees, engineers, PhDs and researchers with an innovative program focused on best practices in the use of the mouse model for biomedical research; this program also addresses the item of continuing professional education consistent with the new European directive requirement for lab animal protection in experiments.
    For Further Information

    3rd RARE DISEASES SUMMER SCHOOL organized by radiz
    Date: 1-3 July, 2015
    Venue: Zurich, Switzerland

    The 3rd radiz Rare Diseases Summer School will focus on a wide variety of subjects in the arena of rare diseases, from disease mechanisms and animal models, to improving diagnoses, to novel therapeutics. There will be lectures and workshops on drug development, model organisms, how to choose clinical endpoints, clinical trials, regulatory aspects, patient registries, patient initiated research, ethical considerations, as well as what rare diseases may tell us about common diseases.
    For Further Information


    What's on Where?

    European Forum for Good Clinical Practice Annual Conference 2015
    Date: 27-28 January, 2015
    Venue: Brussels, Belgium

    “How do we improve health without betraying confidentiality within current and upcoming EU Regulations?” will debate the tensions between confidentiality and transparency in health research.
    For Further Information

    Colloquium on Therapeutic Patient Education (TPE): From practice to research on therapeutic patient education: methodology
    Date: 29 January, 2015
    Venue: Paris, France

    This colloquium will focus on relationships between practice and research in TPE, especially methodological questions pertaining to saidrelationships. The purpose of TPE is to “help patients acquire and hone the skills they need to live with chronic disease”.
    For Further Information

    Development of Medicines For Paediatric And Rare Diseases: Situation Assessment And The Way Forward
    Date: 3-4 February, 2015
    Venue: Basel, Switzerland

    The conference is planned as a kick-off meeting for an annual event to establish a platform for people that work in academic research, commercial drug development, clinical research, patient advocacy, philanthropy, regulatory authorities, & more, and will allow to contribute to a new framework of thinking, interacting and networking with key people that otherwise are not easy to meet.
    For Further Information

    6th International Meeting on Pulmonary Rare Diseases and Orphan Drugs
    Date: 27-28 February, 2015
    Venue: Milan, Italy

    The International Meeting on Pulmonary Rare Diseases and Orphan Drugs is the only European event dedicated to different types of rare pulmonary diseases affecting both parenchymal and vascular structures. The meeting will be an opportunity to exchange and disseminate knowledge among experts in different areas of clinical and basic research in respiratory medicine, in efforts to provide new insights into science and clinical care, thus helping patients and supporting doctors.
    For Further Information

    2nd International Klaus Betke Symposium on Pediatric Hematology
    Date: 6–7 March, 2015
    Venue: Munich, Germany

    The conference will focus on Rare Diseases of the Human Immune System – Neutrophil Granulocytes and Biology of Mitochondria.
    For Further Information

    3rd Edition of the Orphan Drug & Rare Disease Seminar
    Date: 27 March, 2015
    Venue: Lyon, France

    Jointly organized by Eudipharm, F-CRIN and OrphanDev, this Eudipharm training seminar aims at raising awareness among clinical research actors on drug development specificities for rare diseases. This edition will attempt to answer this very “hot topic” by providing tools and solutions to clinical research professionals and project carriers, thanks to the participation of clinical research experts and the authorities.
    For Further Information

    3rd Asia-Pacific Prader-Willi Syndrome Conference 2015: From Better Start to Better Living
    Date: 11-12 April, 2015
    Venue: Melbourne, Australia

    The conference provides opportunity for scientists, professionals, parents and caregivers to join together, providing a forum to share expertise.The conference welcomes anyone who may be interested to participate in this event as the more knowledge and information that can be discovered and shared means a better quality of life for those living with PWS, their medical professionals, carers and families.
    For Further Information

    2nd International GENCODYS Conference on Integrative Networks in Intellectual Disabilities
    Date: 27-29 April, 2015
    Venue: Crete, Greece

    European funded research consortium GENCODYS exploits a multilevel approach to resolve the integrative networks in intellectual disabilities. The conference will bring together about 150 top researchers, medical doctors and patient representatives in the field of Cognitive Research and related activities.
    Talks and submissions for talks have to be related to studies of cognitive dysfunction but can include other fields, namely genetics, cellular, molecular and physiological studies, genomics and epigenomics and bioinformatics.
    For Further Information

    Trisomy 21 Research Society (T21RS) International Conference
    Date: 4-6 June, 2015
    Venue: Paris, France

    T21RS promotes research on Down syndrome and stimulates collaboration between researchers worldwide. The first edition of the T21RS International Conference will be held at the site of the Hôpital de la Pitié-Salpêtrière in Paris. More details will be announced in due course.
    For Further Information

    Date: 6-9 June, 2015
    Venue: Scotland, United Kingdom

    The European Human Genetics Conference (now in its 49th year) is a forum for all workers in human and medical genetics to review advances and develop research collaborations. The ESHG conference is where the latest developments in human genetics are discussed, and where professionals from all parts of human genetics meet.
    For Further Information

    38th European Cystic Fibrosis Conference
    Date: 10-13 June, 2015
    Venue: Brussels, Belgium

    This course is intended for early career medical and paramedical health care workers involved in CF care and /or CF research.
    For Further Information

    Tourette Syndrome Congress 2015
    Date: 24-26 June, 2015
    Venue: London, United Kingdom

    The 1st World Congress on Tourette Syndrome and Tic Disorders is designed for clinicians, researchers , post-doctoral fellows, medical residents and allied healthcare professionals with an interest in current research, diagnosis and treatment of these and related conditions.
    For Further Information

    7th International Conference on Children’s Bone Health
    Date: 27-30 June, 2015
    Venue: Salzburg, Austria

    The International Conference on Children’s Bone Health (ICCBH) meetings provide an international forum for the presentation and discussion of current basic and clinical science in the field of bone metabolism and bone mass in children, adolescents and young adults.
    The call for abstracts opens in September 2014.
    Abstract deadline: 6 February 2015.
    For Further Information

    The 11th International Conference on Developmental Coordination Disorder
    Date: 2-4 July, 2015
    Venue: Toulouse, France

    This 11th congress on Developmental Coordination Disorder (DCD) aims to provide some answers to these important questions: diagnostic criteria, causal factors, prognostic markers, management of DCD and associated disorders.
    For Further Information

    The First Russian Congenital Aniridia Conference
    Date: 3-4 July, 2015
    Venue: Cheboksary, Russia

    The conference will aim at sharing knowledge and experience about Congenital Aniridia by increasing the dialogue between patients and doctors about the problems of congenital aniridia.
    For Further Information

    10th European Cytogenetics Conference
    Date: 4-7 July, 2015
    Venue: Strasbourg, France

    The 10th European Cytogenetics Conference allows all cytogeneticists from Europe and further afield to come together to hear about and discuss the most exciting developments ranging from applications in prenatal or cancer diagnosis to chromosome biology in epigenetics and evolution.
    For Further Information

    The Fourth International Conference on the Glycoproteinoses
    Date: 23-26 July, 2015
    Venue: Missouri, US

    The conference will bring together leading investigators from around the world to discuss the latest advances in understanding the pathophysiology of these rare disorders and the status of the development of new therapies. The intent is to stimulate an interchange of ideas and develop collaborations among investigators with different approaches and expertise.
    For Further Information

    Glycoproteinoses: Fourth International Conference on Advances in Pathogenesis and Therapy
    Date: 23-26 July, 2015
    Venue: Missouri, United States

    The Fourth International Conference on the Glycoproteinoses will bring together leading investigators from around the world to discuss the latest advances in understanding the pathophysiology of these rare disorders and the status of the development of new therapies.
    For Further Information

    Date: 8-11 August, 2015
    Venue: Perth, Australia

    The HGSA ASM 2015 promises to be an exciting meeting with a strong scientific program on the theme of Rare Diseases and Indigenous Genetics. The HGSA is the foremost scientific body for those working in the field of Human Genetics throughout Australia and New Zealand.
    For Further Information

    SSIEM Official Satellite Symposia – Second World Conference on Congenital Disorders of Glycosylation (CDG)
    Date: 28-30 August, 2015
    Venue: Lyon, France

    “The 2nd World Conference on Congenital Disorders of Glycosylation for Families and Professionals: a challenging story of sugar trees” is expected to draw more than 250 attendees consisted of families and the main CDG professional Key Opinion Leaders coming from all countries. Speaker presentations will cover a diverse range of themes previously voted on.
    For Further Information

    Topical Meeting on Osteogenesis Imperfecta
    Date: 28-30 August, 2015
    Venue: Lyon, France

    This seminar will focus on the health issues of adult people with Osteogenesis Imperfecta, especially the non-skeletal problems and hopes to spark an interest in the matter and stimulate further research.
    For Further Information

    2nd International Primary Immunodeficiencies Congress (IPIC)
    Date: 5-6 November, 2015
    Venue: Budapest, Hungary

    The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the Second International Primary Immunodeficiencies Congress (IPIC). This event will build on the successful outcomes of the first IPIC, attended by 400 participants. The congress will consist of a two-day programme and is open to all stakeholders with an interest in clinical management of primary immunodeficiencies (PIDs).
    For Further Information

    13th International Congress of Human Genetics (ICHG) 2016
    Date: 3-7 April, 2016
    Venue: Kyoto, Japan

    Hosted by the East-Asian Union of Human Genetic Societies (EAUHGS) and the Japan Society of Human Genetics, the 13th ICHG will focus on progress in genome analysis technologies and big data in order to explore disease mechanisms and treatment opportunities.
    Registrations open in 2015.
    For Further Information


    Commercial events

    Pharma Pricing and Market Access Congress 2015
    Date: 24-26 February, 2015
    Venue: London, United Kingdom

    The conference provides information on the latest policies affecting market access from payers, HTA authorities and leading industry experts.
    For Further Information

    World Orphan Drug Congress USA 2015
    Date: 3-7 April, 2016
    Venue: Maryland, United States

    The conference will boast of more than 800 industry stakeholders all gathered under one roof.
    For Further Information

    Pan-Omics Summit
    Date: 21-22 May, 2015
    Venue: Massachusetts, United States

    Representatives from big pharma, academic institutions, and government research labs will present data on advances in new technology and case studies on therapeutic targets, molecular diagnostics, and integration of complex data.
    For Further Information

    Epigenomics & Novel Therapeutic Targets Conference
    Date: 21-22 May, 2015
    Venue: Massachusetts, US

    This conference is for the scientists, researchers, laboratory leaders, and managers who are working in the field. This conference allows these experts to share their findings and techniques with colleagues in order to bridge technological and computational gaps that affect datasets, interpretation, and the clinical applications of epigenomics.
    For Further Information

    World Orphan Drug Congress Asia 2015
    Date: 3-4 June, 2015
    Venue: Singapore

    For Further Information


    OrphaNews, The Newsletter of the Rare Diseases Community.
    OrphaNews is supported by the European Commission's DG SANTE (RD-ACTION Joint Action N° 677024) and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Kate Bushby, Ana Rath
    Editor: Divya Unni
    Editors for Scientific Content: Sophie Höhn
    Contact Us
    Editorial Board: Valentina Bottarelli, Victoria Hedley, Yann LeCam, Stephen Lynn, Charlotte Rodwell, Domenica Taruscio, Ariane Weinmann Valentina Bottarelli, Victoria Hedley, Yann LeCam, Stephen Lynn, Charlotte Rodwell, Domenica Taruscio, Ariane Weinmann

    Advisory Editorial Board: Ségolène Aymé, Anna Bucsics, Paul Boom, Bruno Dallapiccola, Jordi Llinares-Garcia, Adam Heathfield, Alastair Kent, Dominique Péton-Klein, Milan Macek, Till Voigtländer

    Orphanet Partner Country Representatives: Romi Armando (Argentina), Kristine Hovhannesyan (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Micheil Innes (Canada), Ingeborg Barisic (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Sirpa Ala-Mello (Finland), Joerg Schmidtke (Germany), Eileen Treacy (Ireland), Annick Raas-Rothschild (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Vaidutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequeiros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Dorra H'mida (Tunisia), Ugur Ozbek (Turkey), Dian Donnai (UK)
    Orphanet - All rights reserved
    Disclaimer : This presentation is part of the project / joint action N° 677024 / RD-ACTION' which has received funding from the European Union's Health Programme (2014-2020).

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