4 July 2013 print
EUCERD update
Spotlight on...
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New Syndromes
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Scoping study published on the current state of European Reference Networks and future implications

There is an ongoing effort on part of the European Commission (EC) to promote quality health care for the citizens of the European Union. However, this can be especially challenging in specialised and complex areas such as rare disease. Establishing reference networks are essential for sharing knowledge as well as facilitating the mobility for expertise. It also helps Member States to provide highly specialised services for patients (especially in rare diseases). However, establishing networks can be complicated, requiring the use of agreed-upon terminologies and maintenance of common standards. In fact, The Directive on patients’ rights in cross-border healthcare (2011/24/EU) Article 12 foresees a common set of criteria that the networks should follow.

To analyse the current situation of reference networks and highly specialised centres in the different European Union countries and to possibly establish a logical, feasible and robust model, a scoping study was performed. The EC and The European Observatory on Health Systems and Policies (World health Organisation) have provided the details of this study in a document entitled Building European Reference Networks in Health Care: Exploring concepts and national practices in the European Union. Although this study was performed within a short time and only provides a rough estimation of the existing networks in Member States, it is still a valuable analysis and provides ample help for building future models of European Reference Networks.

This study assesses the historical context of how certain reference networks have been established in the European Member States. The document provides an examination of the medical conditions or interventions for which reference networks have been developed and the driving force for their establishment. The study also discusses the regulatory processes and the financial implications for establishing these networks. From the analysis, the study also proposes a road map for developing and synthesising reference networks in Europe, keeping in mind the heterogeneity and the needs of the Member States. Additionally the European Committee of Experts for Rare Diseases (EUCERD) has provided, in January 2013, a set of recommendations for setting up reference networks
Read the EUCERD Recommendations on European Reference Networks for Rare Diseases
Read the Cross-Border Directive

EUCERD update
Executive Summary of the 8th Meeting of the EUCERD now available
The executive summary of the 8th Meeting of the European Union Committee of Experts on Rare Diseases, held on 5-6 June 2013 in Luxembourg is now available online.

During the meeting a number of key topics were presented and discussed, including steps towards the establishment of a European platform for rare diseases registries, the role and content of a possible European Research Infrastructure Consortium on rare diseases information for research, the EUCERD opinion on newborn screening, and next steps towards the development of a EUCERD recommendation on genetic testing for rare diseases. For further details


Spotlight on...
Global Alliance now launched to aid in sharing genomic data

The cost of genome sequencing has fallen a million fold, and it is becoming more and more affordable and accessible for the average person. Even though the advances in genome sequencing have provided a wealth of knowledge, the data collected and studied are mostly disorganised and dispersed. Experts contend that there are no agreed-upon standards for representing genetic data or sharing them. Additionally there is currently no common procedures for assuring that patients consent to sharing their information.

To better serve the patient, research and clinical community, fifty representatives from eight countries met earlier this year to discuss how they can work collaboratively so that there is optimal use of the data generated. From this meeting, the delegation decided to develop the global alliance which will develop standards and policies to encourage data-sharing. The alliance also hopes to tackle other ethical issues that have cropped up due to the genomic revolution, such privacy and informed-consent concerns that may prevent researchers from sharing data by utilising cloud-computing platforms and analysis tools. The global alliance plans to base their model on the World Wide Web Consortium, which established HTML standards leading to an unprecedented growth of web pages across the Internet and also the Human Genome Project for its rapid development. The consortium now consists of more than 70 institutions in 13 countries with International Rare Disease Research Consortium (IRDiRC) as one of its members.
Go to the IRDiRC website
Read the Global Alliance White Paper

EU Policy News
EU quality of health care policy: how much is too much interference for the Member States

The role of the European Union (EU) in healthcare has been evolving over time. Although most Member States of the EU prefer healthcare mandates to be decided nationally, the authors in an article published in Health Policy discern a trend towards more EU involvement. This is especially so on policies of access to cross-border care and quality of care. The authors say that EU involvement can be beneficial when it “offers a forum for Member States to learn from each other on the subject of quality of care” especially for the poorer countries but are not in favour of EU dictating all healthcare policies. The author believes that since the accepted level of involvement of the EU in matters of healthcare is still grey and since healthcare policies can be quite “technocratic”, it is difficult to create benchmarks in healthcare by the EU for Member States. Additionally, the authors believe that “setting common enforceable standards may face both resistance from Member States that perceive these standards too high and therefore too expensive to maintain, and Member States that fear their own high quality standards to be replaced by lower ones” . The authors propose a balance of governance efforts between the two entities for quality of care.

An example of a satisfactory balance reached in healthcare decisions between the EU and the Member States is in rare diseases. Each Member State follows its own National Plan for rare disease, but the EU also contributes by overseeing activities such as creating the European Reference Network (see above).
Consult the PubMed abstract


National & International Policy Developments
Guidance Documents and Recommendations
American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders
Microarray methodologies provide genomic data which are correlated with in situ hybridization data to doubly verify genomic aberrations of neoplastic disorders. To aid the laboratories in the consistent and methodical use of these technicyes in diagnostics, the American College of Medical Genetics and Genomics has developed professional standard and guidelines. An article published in the European Journal of Human Genetics, describe these. The authors first describe the advantages and disadvantages of DNA microarrays and then detail provide guidelines and recommendations for “Verification and validation of hardware, software, reagents and processes, means of collecting reference DNA, Quality control and assurance, analysis of data including analytical software” and finally on evaluating and interpreting results. The authors stress that “medical laboratory professionals must be prepared to identify, interpret, and report results with clinical relevance while being mindful of the social, ethical, and legal responsibilities of reporting genetic information”.
Consult PubMed

ACMG position statement on prenatal/preconception expanded carrier screening:
Read the Open Access article
Cysticercosis: guideline of the evidence base for different treatment strategies in adults and children
Consult the Pubmed abstract
To read more about "Cysticercosis"

Neurology. ; 80(15):1424-9 ; April 2013
Emergency guidelines and documents on Orphanet
Emergency guidelines for Classic homocystinuria in English

Bioinformatics, Registries and Data Management
From database to clinical trials: the case of juvenile neuronal ceroid lipofuscinosis (JNCL)

An article published in Contemporary Clinical Trials, the development of a registry for Juvenile neuronal ceroid lipofuscinosis (JNCL; Batten disease) and the subsequent start of clinical trials for the treatment of neuronal ceroid lipofuscinosis (NCL) is described. JNCL is a rare, inherited, fatal lysosomal storage childhood disorder, symptoms of which include vision loss, seizures, dementia, motor impairment, and behavioral and psychological problems. The authors believe that future success in therapeutic attempts to impact symptoms or disease progression relies on improved understanding of the clinical characteristics and nature of the disease process, as well as quantifiable endpoints to judge therapeutic efficacy. With the help of organisations such as Batten Disease Support and Research Association (BDSRA), University of Rochester Batten Center has made noteworthy progress over the past 10 years that has led to the initiation of clinical trials.

The BDSRA is an advocacy group representing families throughout North America who are affected by Batten disease and have enrolled 198 families with 237 NCL-affected children. With the help of the patients enrolled in this database, the Unified Batten Disease Rating Scale (UBDRS) was developed which helps in characterising and quantifying the various disease components and the natural history of disease progression The final form of the UBDRS includes a 20-item Physical Assessment, 12-item Seizure Assessment, 10-item Behavioral Assessment, 10-item Capability Assessment as well as a separate neuropsychological assessment. To validate a non-invasive method for genetic testing the URBC confirmed the genotype of each participant in URBC studies.

Since its initial planning meeting in 2001 with the BDSRA, the URBC has been successful in developing a registry of families interested in future research and recruiting research participants. An RO1 grant from the National Instute of Health at the U.S subsidises travel costs for these patients and a caretaker to the meetings. The authors have stated that “as a long-term objective, the URBC has sought to design and implement a clinical trial in Batten disease”. The URBC has received federal and foundation funding to implement its first randomized, controlled therapeutic clinical trial, which is currently underway.

In addition to the first randomised clinical trial by University of Rochester Batten center, the efforts of the BRSDA registry has lead to two other clinical trials, the progress on which will be announced in their annual conference . Click on the links below for further details on all three clinical trials.
Clinical Trial 1
Clinical Trial 2
Clinical Trial 3
Click on the link for detail on enrol in the registry
Consult the PubMed abstract


Ethical, Legal & Social Issues
Crediting OrphaNews for disseminating information published in the newsletter
OrphaNews has recently faced a disconcerting situation where we discovered that an online + print magazine (http://www.genome-rd.eu/) has published extracts of this newsletter since 2009, without providing due credit. Additionally, addressing this issue with the editor did not yield to a fruitful consequence either. This newsletter is intended for the rare disease community and definitely welcomes wide dissemination of the material published. However, since this newsletter is copyrighted, we ask that due credit is provided to OrphaNews while re-publishing our material. By doing this you will not only be abiding by copyright laws but will also acknowledge the time and hard work that is exerted by us into serving the rare disease community. Please contact the editor for any questions regarding the copyright or details on attributing material published in the newsletter.
U.S supreme court says no to patenting human genes but yes to patenting cDNA
Earlier this year, the ruling by the Federal Court of Australia in favour of Myriad Genetics and Genetic technologies for patenting the genes BRCA1 and BRCA2 had dampened the outlook for the research and diagnostics community considerably. This decision, was based on the contention that the patent was not for the human gene itself but for the extracted genetic material (Read more in OrphaNews). This decision is being appealed at the Federal Court of Appeals in Australia.

However, the U.S Supreme Court has now ruled against the patenting of genes by Myriad Genetics and decreed that “it is undisputed that Myriad did not create or alter any of the genetic information encoded in the BRCA1 and BRCA2 genes”. This ruling may not affect the revenue of Myriad genetics, but will make the test significantly cheaper for patients, as other research institutes and clinics will now also offer the test. As promising as this verdict may appear, the research and clinical community are not celebrating yet due to its ambiguous nature, where cDNA patenting was ruled to be legal. To defend this stance the Supreme court wrote that “the lab technician unquestionably creates something new when cDNA is made”. This dichotomous ruling does not comfort researchers, but it is a step forward and may affect the appeals process in the Federal Court of Australia and possibly bring some good news for Australian patients.
Article in Science Magazine
Article in New York Times
Article in Nature

Defining “incidental findings” and the underlying ethics
A commentary in Genetics in Medicine by James Evans examines the term “incidental findings” and the current controversy surrounding it. The author believes that it is incorrect to think that incidental findings in other medical settings are “stumbled upon” but in fact they are systematically and methodically ascertained. For elucidating his point of view the author gives the example of MSH2 screening in Lynch syndrome. The author believes that only “known mutations (and in appropriate genes, nonsense and frame-shifting mutations) should be sought, otherwise, the number of false-positives generated would be overwhelming”. Likewise, the author stresses that clinicians must be conscious of the exisiting evidence regarding the list of genes to be queried. The author considers the current list of mutations proposed by the ACMG as a “good start”, but also argues that it could be even shorter and provides the example of Li–Fraumeni syndrome, where preventative measures are scant but ACMG has included the mutation that leads to Li-Fraumeni syndrome to be included. However, overall the author is satisfied with the ACMG recommendations on incidental findings, as he believes that they “are consistent with long-established norms of medical practice and bring genomics in line with the rest of medicine”.
Read the Open Access commentary

Discussion of Ethics of Non-invasive prenatal testing for single gene disorders using hypothetical scenarios
In an ethics commentary on Non-invasive prenatal testing for single gene disorders published in European Journal of Human Genetics, four hypothetical scenarios are presented. The authors highlight “how ethical ideals of respect for autonomy, privacy and fairness may come into play when offering non-invasive prenatal testing for single gene disorders”. The authors believe that the potential impacts of non-invasive prenatal testing for single gene disorders on clinical practice has implications for future policy and guidelines for prenatal care.
Consult the PubMed abstract


New Syndromes

A novel syndrome of hypohidrosis and intellectual disability linked to COG6 deficiency
In this study, a large consanguineous Saudi family with an unusual constellation of severe intellectual disability, hypohidrosis, abnormal teeth, and acquired microcephaly is described. A homozygous splicing mutation in COG6 was revealed which results in aberrant splicing and severe deficiency of the protein. Four additional patients representing two families of the same tribal origin as the original family were found to have the same mutation, confirming a founder effect.
Consult the Pubmed abstract

J Med Genet. ; 50(7):431-6 ; July 2013
Mutation in ADAT3 causes a novel autosomal recessive form of intellectual disability with strabismus
Authors showed the combined use of exome sequencing and homozygosity mapping to report a novel form of intellectual disability with strabismus. A novel intellectual disability disease gene that encodes an essential protein for a highly specialised form of RNA editing was revealed. A single missense mutation in ADAT3 was identified in all studied families on an ancient ancestral haplotype. For the first time, a human mutation in the t-RNA editing machinery was found. This finding expands the landscape of pathways involved in the pathogenesis of intellectual disability.
Consult the Pubmed abstract

J Med Genet. ; 50(7):425-30 ; July 2013
Multisystemic failure including renal tubulopathy caused by a homozygous mutation in TWINKLE in three siblings
Three deceased infants from a Pakistani consanguineous family had a similar new phenotype of cholestatic liver disease, hypotonia, severe failure to thrive, recurrent vomiting, renal tubulopathy, and a progressive neurodegenerative course. Exome sequencing revealed a homozygous novel mutation in TWINKLE gene. The hepatocerebral phenotype is well recognised in association with recessive mutations in TWINKLE gene. The feature of renal tubulopathy adds to the multisystemic presentation in these patients and further demonstrates an expansion of the phenotype in mitochondrial DNA depletion syndrome associated with TWINKLE gene mutations.
Consult the Pubmed abstract

Mol Genet Metab. ; 108(3):190-4 ; March 2013

New Genes

Leukoencephalopathies due to ClC-2 chloride channel deficiency
Consult the Pubmed abstract
Lancet Neurol. ; 12(7):659-68 ; July 2013
Familial exudative vitreoretinopathy: ZNF408 mutation identified in a large Dutch family
Consult the Pubmed abstract
To read more about "Familial exudative vitreoretinopathy"

Proc Natl Acad Sci U S A. ; 110(24):9856-61 ; June 2013
Autosomal recessive limb-girdle muscular dystrophy caused by a novel homozygous splice site mutation in DES in two affected individuals of a consanguineous family
Consult the Pubmed abstract
J Med Genet. ; 50(7):437-43 ; July 2013
C3 glomerulopathy: description of a novel pathogenic mechanism caused by a unique CFHR1 mutation
Consult the Pubmed abstract
J Clin Invest. ; 123(6): 2434–2446 ; June 2013
Congenital dyserythropoietic anemia type 3 is caused by a novel mutation in kinesin family member, KIF23
Consult the Pubmed abstract
To read more about "Congenital dyserythropoietic anemia type 3"

Blood. ; 121(23):4791-9 ; June 2013
Aplasia cutis congenital verticis: novel link between BMS1, the cell cycle, and skin morphogenesis
Consult the Pubmed abstract
To read more about "Circumscribed cutaneous aplasia of the vertex"

PLoS Genet. ; 9(6):e1003573 ; June 2013
LINS, a modulator of the WNT pathway, is an indispensable gene to human cognition
Consult the Pubmed abstract
Orphanet J Rare Dis. ; 8(1):87 ; June 2013
46,XY partial gonadal dysgenesis: novel androgen receptor mutation identified in one family
Consult the Pubmed abstract
To read more about "46,XY partial gonadal dysgenesis"

J Clin Endocrinol Metab. ; 98(6):2223-9 ; June 2013
Acute generalised exanthematous pustulosis: recessive mutations in the IL36RN gene
Consult the Pubmed abstract
To read more about "Acute generalized exanthematous pustulosis"

J Invest Dermatol. ; 133(7):1904-7 ; July 2013
Predisposition to encephalopathy with febrile status epilepticus due to genetic variation in ADORADA2
Consult the Pubmed abstract
Neurology. ; 80(17):1571-6 ; April 2013
Idiopathic ventricular fibrillation, not Brugada type: non-synonymous polymorphism in SEMA3A as a risk factor
Consult the Pubmed abstract
To read more about "Idiopathic ventricular fibrillation, not Brugada type"

PLoS Genet. ; 9(4):e1003364 ; April 2013
Congenital pulmonary venous return anomaly: identification of SEMA3D signalling defects
Consult the Pubmed abstract
To read more about "Congenital pulmonary venous return anomaly"

Nat Med. ; 19(6):760-5 ; June 2013
Amyotrophic lateral sclerosis: involvement of CREST variants
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

Nat Neurosci. ; doi: 10.1038/nn.3412 ; May 2013
Congenital heart disease: a marked excess of de novo mutations in histone-modifying genes
Consult the Pubmed abstract
Nature. ; 498(7453):220-3 ; June 2013
Meckel syndrome: likely pathogenic mutation in three novel candidate disease genes
Consult the Pubmed abstract
To read more about "Meckel syndrome"

Eur J Hum Genet. ; 21(7):762-8 ; July 2013
Oculocutaneous albinism: exome sequencing identifies SLC24A5 as a candidate gene
Consult the Pubmed abstract
To read more about "Oculocutaneous albinism"

J Invest Dermatol. ; 133(7):1834-40 ; July 2013
Pituitary adenoma and pheochromocytoma/paraganglioma are associated with familial SDHA mutation
Consult the Pubmed abstract
J Clin Endocrinol Metab. ; 98(6):E1103-8 ; June 2013

Research in Action

Clinical Research
Atypical hemolytic uremic syndrome: terminal complement inhibitor eculizumab was associated with significant time-dependent improvement in renal function
Consult the Pubmed abstract
To read more about "Atypical hemolytic uremic syndrome"

N Engl J Med. ; 368(23):2169-81 ; June 2013
Urea cycle disorder: ammonia control and neurocognitive outcome with glycerol phenylbutyrate
Consult the Pubmed abstract
To read more about "Carbamoylphosphate synthetase deficiency"
To read more about "Ornithine transcarbamylase deficiency"
To read more about "Citrullinemia type I"
To read more about "Argininemia"
To read more about "Argininosuccinic aciduria"
To read more about "Hyperornithinemia-hyperammonemia-homocitrullinuria"

Hepatology. ; 57(6):2171-9 ; June 2013
Polyneuropathy associated with IgM monoclonal gammopathy with anti-MAG: rituximab is ineffective in improving inflammatory neuropathy
Consult the Pubmed abstract
To read more about "Polyneuropathy associated with IgM monoclonal gammopathy with anti-MAG"

Neurology. ; 80(24):2217-2225 ; June 2013
Mucopolysaccharidosis type 2: improvement in growth rate following idursulfase treatment
Consult the Pubmed abstract
To read more about "Mucopolysaccharidosis type 2"

Mol Genet Metab. ; 109(1):41-8 ; May 2013
Myelofibrosis with myeloid metaplasia: review and discussion of published and presented survival data on patients treated with ruxolitinib
Consult the Pubmed abstract
To read more about "Myelofibrosis with myeloid metaplasia"

Blood. ; 121(24):4832-7. ; June 2013
Kennedy disease: positive effect of clenbuterol on the disease progression
Consult the Pubmed abstract
To read more about "Kennedy disease"

Neurology. ; 80(23):2095-2098 ; June 2013
Gene Therapy
Rescue of the disease phenotypes of X-linked retinoschisis and Leber’s congenital amaurosis with a new evolved adeno-associated virus variant
Consult the Pubmed abstract
To read more about "X-linked retinoschisis"
To read more about "Leber congenital amaurosis"

Sci Transl Med. ; 5(189):189ra76 ; June 2013
Therapeutic Approaches

Transthyretin-related familial amyloid cardiomyopathy: AG10 inhibits amyloidogenesis and cellular toxicity
Consult the Pubmed abstract
To read more about "Transthyretin-related familial amyloid cardiomyopathy"

Proc Natl Acad Sci U S A. ; 110(24):9992-7 ; June 2013
Primary effusion lymphoma: strong rationale for the combined use of bortezomib and suberoylanilidehydroxamic acid
Consult the Pubmed abstract
To read more about "Primary effusion lymphoma"

J Clin Invest. ; 123(6):2616-28 ; June 2013
Mucopolysaccharidosis type 1: enzyme replacement therapy started at birth improves outcome in difficult-to-treat organs
Consult the Pubmed abstract
To read more about "Mucopolysaccharidosis type 1"

Mol Genet Metab. ; 109(1):33-40 ; May 2013
Diagnostic Approaches

Three Clinical Utility Gene Cards published in the European Journal of Human Genestic
EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases. The European Journal of Human Genetics has published three new Clinical Utility Gene Cards for:

Incontinentia pigmenti
Campomelic dysplasia
Rothmund–Thomson syndrome
List of Clinical Utility Gene Cards

Isolated NADH-CoQ reductase deficiency: association of NUBPL mutations with a unique, consistent, and recognisable magnetic resonance imaging pattern
Consult the Pubmed abstract
To read more about "Isolated NADH-CoQ reductase deficiency"

Neurology. ; 80(17):1577-83 ; April 2013
Central nervous system lymphomas: CXCL13 and IL-10 as potentially important biomarkers
Consult the Pubmed abstract
To read more about "Diffuse large B-cell lymphoma of the central nervous system"
To read more about "Primary central nervous system lymphoma"

Blood. ; 121(23):4740-8 ; June 2013

Patient Management and Therapy
Immune thrombocytopenic purpura: increased risk of venous thrombosis and sepsis after splenectomy
Consult the Pubmed abstract
To read more about "Immune thrombocytopenic purpura"

Blood. ; 121(23):4782-90 ; June 2013
PMM2-CDG syndrome: assessment of the occurrence of specific risk factors for thrombotic events
Consult the Pubmed abstract
To read more about "PMM2-CDG syndrome"

Mol Genet Metab. ; 109(1):107-11 ; May 2013

Orphan Drugs
Regulatory News
Two medicinal products intended to treat rare diseases approved by EMA
RoActemra has now been approved by the European Medicines Agency (EMA) to treat a rare form of arthritis in children and HyQvia have been approved for the treatment of myeloma or chronic lymphocytic leukaemia with severe secondary hypogammaglobulinaemia and recurrent infections. Neither RoActemra or HyQvia have received orphan designations from the EMA.
Learn more about RoActemra
Learn more about HyQvia

Japan approves Avastin for brain cancer
Avastin (bevacizumab) has been approved by The Japanese Ministry of Health, Labour and Welfare (MHLW) as an adjunct treatment for malignant glioma (brain cancer), newly diagnosed glioblastoma (GBM) in combination with radiotherapy and temozolomide chemotherapy. Although, Avastin has previously been withdrawn as a treatment for breast cancer, due to the limited treatment options available to treat glioma and glioblastoma this avastin appears to be of promise to these patients.
Read the Roche press release

22 positive opinions recommending orphan designation at the June 2013 COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted ten positive opinions issued at the June 2013 COMP meeting for the treatment of:

• amyotrophic lateral sclerosis (2 separate medicinal products)
• pulmonary alveolar proteinosis
• B-lymphoblastic leukaemia/lymphoma
• pancreatic cancer
• follicular lymphoma
• malignant thymomas
• plasma cell myeloma
• ataxia telangiectasia
• limbal stem cell deficiency
• ovarian cancer
• hyperargininaemia
• carbamoylphosphate synthase-1 deficiency
• ornithine translocase deficiency
• citrullinaemia type 2
• argininosuccinic aciduria
• citrullinaemia type 1
• N-acetylglutamate synthetase (NAGS) deficiency
• ischaemia/reperfusion injury associated with solid organ transplantation
• follicular lymphoma
• lymphoplasmacytic lymphoma
• hepatitis B re-infection following liver transplantation
Consult the European Register of Designated Orphan Medicinal Products
Consult the Orphanet list of orphan drugs authorised for marketing in Europe

Political and Scientific News
French Brugada Association calls for enquiry into the depleting amount of Quinidine in the market
In an open letter published in Journal of the American College of Cardiology, Pierre Garçonnat and Blandine Subra- Executive Vice President and President of the Association of Brugada syndrome France respectively- have expressed concern over the fact that Quinidine may soon be impossible to obtain in France. Quinidine is an important drug to stabilise arrhythmic storms in patients with Brugada syndrome. According to the authors, even Sanofi, manufacturer of the anti-arrhythmic drug: sérécor (active ingredient: hydroquinidine), admit to the direness of the situation. This lack of quinidine has been a matter of international disquiet as multiple articles have been published since 2007 involving this topic (PubMed links to access the articles). Many patients have contacted The French Brugada Association for help and the authors are asking “authors and clinicians to provide us with appropriate information about the beneficial effects of quinidine in their patients with Brugada syndrome”.
Link to French Brugada Association
Consult PubMed

Experts of chronic myeloid leukaemia Nature Biotechlogy addressing excessive drug prices

Experts of chronic myeloid leukaemia (CML) have published an article in Blood protesting the price for cancer drugs particularly for CML. The article addresses the various intricate factors involved in pricing drugs and makes their case for lowering drug prices and for maintaining “sound long term healthcare policies”. They believe that the exorbitant prices of these drugs are causing substantial harm to the patients and an urgent dialogue involving all parties concerned is required.

Reiterating the concerns of these experts, the editorial published in Nature Biotechnology also addresses “the plight of a growing cadre of leukemia patients who no longer can afford to pay for their treatments (while) price tags for drugs entering the US market continue to skyrocket”. The editorial points to the exponential increase in the prices of drugs which now can cost a patient an upward of US$ 200,000 per year a tendency observed in several approved drugs the past few months alone. Although, in some cases the exorbitant prices are reflective of the developmental cost for the drug, the editorial object to the “companies seeking price premiums for drugs that have only marginal benefits and are not new drugs, but year-on-year price increases for older drugs”. The editorial also point that insurance companies do cover the patients who need the drugs in the U.S, but the insurance companies routinely make the patients pay by charging them “higher insurance premiums and deductibles, additional coverage exclusions or limits, and increasing copayments”. Nature Biotechnology hopes that industry organizations and company management will give a serious consideration to initiatives that reduce the burden on patients.
Read the open access article of experts opinion on drug prices for CML
Read the open access Nature Biotechnology editorial



Jérôme Lejeune Foundation - Research Projects
The foundation will support projects of basic or clinical research (neuroscience, behavior, genetics, molecular biology, therapy, etc.) that is intended to result in the discovery of treatments to improve the capacity of patients with genetic diseases with intellectual disabilities, especially the Trisomy 21 (except autism). Projects oriented towards clinical studies will be given priority. Application deadline is: 19 August 2013 .
Consult the website
For further information email conseilscientifique@fondationlejeune.org

Care-for-Rare Science Award 2013

The Histiocytosis Association have announced the launch of the 2013 Request for Research Proposals (RFRP). Each year, the Association awards individual research grants to promote better treatments and a cure for histiocytic disorders for scientists around the world. Proposals for scientific research will be accepted for studies into the causes, mechanisms, and improved means of treatment for histiocytic disorders. They will be evaluated on the basis of science, feasibility, and relevance. Application deadline is 31 July 2013.
For any additional questions or concerns, please contact grants@histio.org.

NORD announces seed grants for rare disease research
NORD has announced funding opportunities in 6 areas of rare disease research. NORD has invited applicants from within the US and overseas to apply. Full proposals are due by 11 September 2013. Researchers with projects in the following areas are encouraged to apply

RFPs for Pseudomyxoma Peritonei (PMP), Spring 2013
Two grants are available through NORD ($50,000/grant) for research related to Pseudomyxoma Peritonei (PMP).

RFP for Growth Failure in Children with Cardiofaciocutanous (CFC) Syndrome
Funding is available ($30,000) for research on growth failure in children with cardiofaciocutaneous (CFC) syndrome.

RFP for Glycine Encephalopathy, aka Nonketotic Hyperglycinemia, Spring 2013
Funding for research related to Glycine Encephalopathy, aka Nonketotic Hyperglyinemia, is available through NORD's Research Seed Grant Program ($34,000).

RFP for Adult Primary Lateral Sclerosis (PLS)
Funding is available ($30,000) for research on Primary Lateral Sclerosis (PLS).

RFP Available for Research Related to Dubowitz Syndrome
Funding is available ($30,000) for research on Dubowitz Syndrome
For further details


Partnersearch, Job Opportunities
Grantholder position for the establishment of the European Technological Platform on Rare Diseases
The JRC Institute for Health and Consumer Protection has started recruitment for the Grantholder position for establishing the European Technological Platform on Rare Diseases. The tasks will involve liaising with the Rare Diseases expert communities and patient organisation. Candidates with extensive experience working in the field of RD and/or epidemiology are encouraged to apply: For further details

Courses & Educational Initiatives
International Summer School “Clinical practice guidelines on rare diseases”
Date: 8-12 July, 2013
Venue: Rome, Italy

Istituto Superiore di Sanità is inviting applications from participants who would like to learn more about development process of clinical practice guidelines.
The following topics will be covered:
o Identifying key clinical issues to be included (scope)
o Developing review questions using PICO and planning the systematic review
o Identifying evidence: formulating, executing and documenting a search strategy
o Assessing the quality of relevant studies, summarizing and interpreting the body of evidence to make recommendations
o Obtaining formal consensus in the absence of evidence (Delphi-like method)
o Appraising synthesis documents: guidelines and systematic reviews
The course format consists of brief presentations followed by individual or small group exercises.
This course is free of charge and application/registration is currently open. Please, feel free to circulate this information to those who may have an interest in attending.
For further details

The 1st radiz Rare Diseases Summer School
This course scheduled for 4-6th July 2013 in Zurich, Switzerland will focus on a wide variety of subjects in the area of rare diseases, from disease mechanisms and animal models, to improving diagnoses, to novel therapeutics. These will be presented in the form of lectures by international experts on rare diseases. Please apply by sending a short CV, a letter of motivation including a brief description of your project or research interest, and one letter of recommendation to For further information email saskia.karg@kispi.uzh.ch. For further details
International Summer School Rare Disease and orphan Drug Registries
Date: 16-20 September 2013
Venue: Rome, Italy

Application Deadline: 15 July 2013 Further Information about this course can be found on the epirare website For further details

Orphan Drug & Rare Disease Seminar: accelerating access to therapeutic innovation
Date: 17-18 October 2013
Venue: Marseille, France

This event, jointly organised by Eudipharm, F-Crin and OrphanDev, will aim to address issues that to help fill the current discrepancies in translational research for rare diseases and creating awareness of clinical research sectors. For further details


What's on Where?

Haemophilia centres certification system across Europe
Date: 11 July 2013, 9:00 a.m. - 1:30 pm
Venue: Rome, Italy

The objective of the Meeting is the exchange of accreditation and certification experiences in use in different EU Member States. During the event the new European Standards for Haemophilia Centres developed in the context of EUHANET project (www.euhanet.org) will be presented to be followed by a national seminar for Italian Regional Authorities on the implementation of a guideline for HCs institutional accreditation approved by the State-Regions Agreement of March 12, 2013
For further details

8th International Prader-Willi Syndrome Conference
Date: 17-21 July 2013
Venue: Cambridge, UK

An opportunity for all involved worldwide in research, working or living with people with PWS to present current research and explore best practice in clinical and day to day management of PWS.
For further details

International Symposium on Urea Cycle Disorders (UCD)
Date: 1-2 September 2013
Venue: Barcelona, Spain

The symposium will focus on recent advances in UCD clinical and translational research which provide insights into the pathophysiology of these disorders. These advances will form the basis for the development of novel therapeutic approaches for UCDs that aim at decreasing mortality and preventing the effects of hyperammonemia on brain function. The satellite symposium will provide a forum for international researchers, clinicians, trainees and patients’ families to share and discuss research in UCD. This meeting will be the first formal joint meeting between the Urea Cycle Disorders Consortium (UCDC) and the European-Registry and Network for Intoxication Type Metabolic Disease (E-IMD).
For further details

International Congress of Inborn Errors of Metabolism
Date: 3-6 September 2013
Venue: Barcelona, Spain

The organisers have put together an ambitious and high level scientific programme, allowing the participation of multidisciplinary delegates where important topics and cutting edge research on inborn errors of metabolism will be discussed.
For further details

Orphan Drugs Summit 2013
Date: 11-13 September 2013
Venue: Copenhagen, Denmark

This commercial event will highlight several burning topics revolving market authorisation of Orphan Medicinal Products such as market access, regulatory framework, clinical trial development as well as financing.
For further details

2nd Conference of 'EB-CLINET - Clinical Network of EB Centres and Experts'
Date: 17-18 September 2013
Venue: Salzburg, Austria

The conference will present and discuss the work packages initiated during the 2012 EB clinet meeting.
For further details

2nd International Symposium on Hypothalamic Hamartomas
Date: 20-21 September 2013
Venue: Marseille, France

This Symposium will provide a platform for collaboration and education and offer an opportunity to set a road-map for the next ten years of treatment and research for the treatment of hypothalamic hamartomas. Abstract Deadline: 15 July
For further details

EUROPLAN National Conferences Finland
Date: 21 September 2013
Venue: Helsinki, Finland

Organised by Finnish Rare Diseases Alliance (HARSO)

Second Symposium on ATP1A3 in disease Genotype/Phenotype Correlations, modelling and identification of potential targets for treatment
Date: 23 - 24 September 2013
Venue: Rome, Italy

The aim of this Symposium is to present the progress of research undertaken on Alternating Hemiplegia of Childhood (AHC), after the finding of the ATP1A3 gene as the primary cause of this rare neurological disease. The symposium also aims to promote international collaboration and recruit new teams of researchers. Clinical aspects of the disease such as genotype/phenotype correlations will also be highlighted as well as possibilities towards the establishment of clinical trials for AHC.
For further details

1st Iberoamerican Conference on Rare Diseases
Date: 24 - 25 September 2013
Venue: Brasilia, Brasil br>
This event will be held at University of Brasilia, Catholic University of Brasilia, where stakeholders of rare diseases nationally and internationally will be coming together to share their views .
For further details

EUROPLAN National Conferences Poland
Date: 27-28 September 2013
Venue: Warsaw, Poland

Organised by Polish National Forum for rare diseases therapy (ORPHAN)
For further details visit www.rzadkiechoroby.pl/europlan

EUROPLAN National Conferences Italy
Date: 26 September 2013
Venue: Rome, Italy


Mitochondrial Disease: Translating biology into new treatments
Date: 2-4 October 2013
Venue: Cambridge, UK

This is a brand new conference that will discuss mitochondrial medicine. During this interactive conference several experts will speak about translational mitochondrial medicine. Abstracts are due by 16 July 2013 and the registration deadline is on 20 August 2013.
For further details

US Conference on Rare Diseases & Orphan Products: The New Era in Healthcare
Date: 7-9 October 2013
Venue: Maryland, United States of America

This annual meeting will be attended by stakeholders in the rare disease community - patients, patient organizations, researchers, drug and device companies, investors, thought leaders and government.
For further details

The 10th Balkan Congress of Human Genetics and 2nd Alps Adria Meeting on Human Genetics (AABC2013)
Date: 10-12 October 2013
Venue: Bled, Slovenia

This congress will deal with several issues pertaining rare genetic disorders, with sessions focusing exclusively on rare human disease.
For further details

Orphan Drugs and Rare Diseases
Date: 14-15 October 2013
Venue: London, UK

This commercial orphan drugs conference focuses on the current rare diseases drug development landscape where world leading expert speaking faculty will highlight cutting edge research via case studies taking place in previously untreatable patients with highly rare diseases, current regulatory policies involving the FDA & EMA, new drug discoveries and partnerships in clinical trials and drug development with patient groups.
For further details

3rd European Rett Syndrome Conference Maastricht, “Research Update & Preventive Management”
Date: 17-19 October 2013
Venue: Maastricht, The Netherlands

This conference aims to gather renowned researchers and clinicians working in the area of Rett Syndrome, to encourage interdisciplinary international cooperation. The conference also aims to provide stakeholders with the latest information on treatment of symptoms as well as preventative manangement.
For further details

Thalassemia International Federation World Congress
Date: 19-23 October 2013
Venue: Abu Dhabi, United Arab Emirates

Topics for this conference includes “all aspects of prevention, management and care of thalassemia and sickle cell disease and a one-day patient programme”.
For further details

The 2nd International Workshop Rare Disease and Orphan Drug Registries
Date: 21-22 October 2013
Venue: Rome, Italy

Application Deadline: 15 July 2013 Further Information about this course can be on the epirare website For further details

World Cord Blood Congress IV and Innovative Therapies for Sickle Cell Disease
Date: 24-27 October 2013
Venue: Monaco, Principauté de Monaco

This international conference will cover a wide range of topics including cord blood transplant in adults and children, the role of HLA in cord blood transplant, stem cells, cord blood banking and regulatory issues. The scientific programme comprises of an international panel of distinguished scientitists and clinicians with a special session on sickle cell disease. This conference is open to all professionals working in fields related to cord blood biology and clinical applications from both public and private sectors, including physicians, research scientists, technicians, data analysts, nurses as well as healthcare policy makers.
For further details

EUROPLAN National Conferences Hungary
Date: 25-26 October 2013
Venue: Budapest, Hungary


HGV2013: 14th International Meeting on Human Genome Variation and Complex Genome Analysis
Date: 30 September - 2 October, 2013
Venue: Seoul, South Korea
HGV2013 will bring together human geneticists from around the world to explore and share the latest in genetic technology, cancer genetics, population genetics, genomic medicine and more. This 3 day meeting will include plenary talks from over 25 high-profile speakers with over 200 posters, a student-mentor luncheon, a journal publishing workshop, and plenty of networking opportunities.
For further details

First International Primary Immunodeficiencies Congress (IPIC)
Date: 7-8 November 2013
Venue: Estoril, Portugal
The International Patient Organisation for Primary Immunodeficiencies (IPOPI) announces the First International Primary Immunodeficiencies Congress (IPIC), a congress for all stakeholders with an interest in primary immunodeficiencies (PIDs). IPIC will provide a two-day programme focusing on clinical developments including PIDs pathogenesis, treatment, management of complications and more. Access to diagnosis and care, SCID newborn screening and other key world developments will also be addressed.
For further details

EUROPLAN National Conferences The Netherlands
Date: 7-8 November 2013
Venue: Amsterdam, The Netherlands

Organised by Dutch Genetic Alliance (VSOP)

World Orphan Drug Congress 2013
Date: 14 November 2013
Venue: Geneva, Switzerland

This commercial conference and exhibition bringing together buyers, sellers and key influencers from across the orphan and rare disease industry. Having welcomed over 1000 orphan and rare disease stakeholders in only its 3 year history, the event in Europe’s logical choice for Biotech and Pharma orphan drug players who want to meet Rare Disease Networks, Patient Groups, COMP Members, HTA Experts, Regulators and Payers.
For Further Information

EUROPLAN National Conferences Lithuania
Date: 14 November 2013
Venue: Vilnius, Lithuania

Organised by Ministry of Health

EUROPLAN National Conferences Luxembourg
Date: 20 November 2013
Venue: Luxembourg

Organised by Luxembourg Alliance for Rare Diseases and Neuro Muscular Diseases (ALAN)

XIIIth International Congress on Neuromuscular Diseases (ICNMD)
Date: 5-10 July 2014
Venue: Nice, France

ICNMD is regular meeting of the Research Group on Neuromuscular Diseases-World Federation of Neurology that takes place every 4 years for the past 50 years. This conference will present a unique opportunity for sharing scientific advances by those involved in the fields of improving care, understanding disease pathogenesis, and developing innovative treatments in muscle, neuromuscular junction, peripheral neuropathies and motor neuron diseases.
For further details


Orphanews International, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews International is supported by the European Commission's DG SANCO (EUCERD Joint Action N° 2011-22-01)
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Divya Unni
Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Barbara Cagniard, Virginie Hivert, Sophie Höhn, Helena Kaariainen, Odile Kremp, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Jaroslaw Waligora

EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Rumen Stefanov (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Zsuzsanna Lengyel (Hungary), Thor Thorarinsson (Iceland) , John Devlin (Ireland), Annick Raas-Rotshild (Israel), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Romalda Baranauskiene (Lithuania) , Yolande Wagener (Luxembourg), Miriam Dalmas (Malta), Jolande Huizer (Netherlands), Stein Are Aksnes (Norway), Jacek Gralinski (Poland), Alexandre Diniz (Portugal), Emilia Severin (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), To be nominated (Sweden) , Sabina Gallati (Switzerland), Edmund Jessop (UK)
EUCERD ECDC Representative: Andrew Amato
EUCERD Patient Organisation Representatives: Dorica Dan, Yann Le Cam, Christel Nourissier, Bianca Pizzera
EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
EUCERD European Commission Participants: Catherine Berens, Iiro Eerola, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Jaroslaw Waligora, Antoni Montserrat Moliner, Michael Huebel, Bruno Sepodes (EMA-COMP)

Orphanet Partner Country Representatives: Tamara F. Sarkisian (Armenia), Hugh Dawkins (Australia), Till Voigtlander (Austria), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Joerg Schmidtke (Germany), Helen Michelakakis (Greece), András Becskeházi (Hungary), Andrew Green (Ireland), Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbané (Lebanon), Viadutis 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), Ugur Ozbek (Turkey), Dian Donnai (UK)
For more information on the European Union Committee of Experts on Rare Diseases
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