16 October 2014 print
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Orphanet unveils major and unique new scientific content on epidemiology, genetics and categorisation of clinical entities

Orphanet has recently incorporated new data to offer the best possible service in terms of information on rare diseases, and new functionalities to make searches for information on rare diseases more user-friendly. The additional data and tools aim to fine-tune and improve the accuracy of disease categorisation, disease epidemiology and the genetic contribution to disease onset. Most of the new data is accessible for download on Orphadata for reuse by investigators, policymakers and industry. The new data will also enrich ORDO, Orphanet’s rare disease ontology, over the next few months.

A better categorisation of diseases and a better characterisation of their equivalence in other terminologies

The database entries in Orphanet are diseases, but also include syndromes, anomalies, malformations, groups of diseases and disease sub-types. From now on, each clinical entity is assigned precisely one of these categories, allowing more accurate information on their exact number. Other precisions include updates on diseases now recognised under a different name or as part of another disease. Orphanet will redirect users towards the disease now accepted according to the literature. Similarly, a link on the website will redirect users to existing information on disease sub-types.

Orphanet has already generated alignments between ORPHA nomenclature and other terminologies, such as OMIM or other coding systems, including ICD-10, SNOMED-CT, MedDRA, MeSH and UMLS. Alignment between Orphacodes and ICD-10 has now been completed. It is now indicated whether terminology equivalence is exact or partial. This information will improve interoperability between databases that use different nomenclatures.

Extended genetic data

Genetic entries have also been expanded to provide information on the protein coded by the gene and the gene, the specific chromosomal location and all former symbols and synonyms.

Information on the relationship between genes and diseases was already provided, according to the following categories: “causal gene”, “modifier gene” or “susceptibility causing gene”. Functional information has been added, where available, on germline causal loss-of-function or gain-of-function mutations (for those that can be transmitted to future generations and are sufficient to cause disease). Such information is of particular interest for therapeutic research.

Large quantity of new epidemiological data

Disease hereditary patterns and age of onset categories have been refined for more accurate information. Prevalence, annual incidence, prevalence at birth and lifetime prevalence data are now available for download on Orphadata, in addition to prevalence intervals already available. Minimum, maximum and mean figures for each item are documented according to geographic zones where the information is available. The number of cases or families reported in the literature is also indicated for very rare diseases, and data sources and validity are supplied.

These new epidemiological entries available on a large number of rare diseases constitute a unique and global source of information which we hope are useful to all concerned users, namely policymakers, the research community and industrial actors involved in orphan drug development.


EU Policy News

The European Commission calls for candidates to represent patient organisations on the Committee for Orphan Medicinal Products
The European Commission is inviting candidates to apply for three positions as patient organisation representatives on the Committee for Orphan Medicinal Products (COMP). The COMP plays a central role at the European Medicines Agency (EMA) to designate orphan medicinal products. Article 4(3) of Regulation (EC) No 141/2000 of the European Parliament and Council on orphan medicinal products states that “The Committee shall consist of one member nominated by each Member State, three members nominated by the Commission to represent patients' organisations and three members nominated by the Commission”.

The current three patient representative members of COMP’s term of office will end in June 2015. Candidates for the next term must be available for three years and willing to travel to London for monthly meetings. Candidates should display experience to represent patient organisations at a European level and demonstrate competencies relevant to the Committee’s mission. The main task of the Committee is to examine applications for the designation of medicinal products as orphan medicinal products.

The deadline for application submission is 1st December, 2014

For further information and access to application forms


EMA launches a pilot project to involve patients in medicines’ benefit/risk assessment discussions
On 26th September, the European Medicines Agency (EMA) announced the launch of a pilot project to include patients in discussions with the Committee for Medicinal Products for Human use (CHMP) to assess drug benefits and risks. The project aims to increase transparency and patient awareness of the medicinal product assessment process.

Two patients suffering from a rare genetic blood disorder, erythropoietic protoporphyria (EPP), were invited to the September meeting to discuss their condition with the CHMP. The Committee will integrate patient input into their assessment of afamelanotide, a novel drug to protect EPP photosensitive patients from sunlight and UV radiation.

The EMA will run the pilot project for one year in order to assess outcome and feasibility, address organisational aspects, integrate CHMP and patient feedback, and propose long term implementation of the project.

Read the EMA press release


National & International Policy Developments

Other European news
Report from the international workshop on recommendations and criteria for European Reference Networks in the field of neuromuscular disorders

In October 2013, clinicians, scientists and patient representatives in the neuromuscular field discussed implementing European Reference Networks (ERNs) for neuromuscular diseases (NMD) with pilot ERN representatives at the 200th European Neuro Muscular Centre (ENMC) International Workshop. In the workshop report, published in Neuromuscular Disorders, Evangelista et al. discuss country experiences and the opportunities and challenges to establish ERNs in the field of NMDs.

NMDs are complex, chronic and multi-system disorders, requiring multi-disciplinary care. According to a study conducted in 2012 by NEUROMICS, around 500,000 to 600,000 patients suffer from rare NMDs in Europe. Because treatment is heterogeneous within and across countries, ERNs would contribute towards improving patient diagnosis and disease management, and mitigate burden on healthcare systems.

Based on studies assessing neuromuscular centres across Europe (Belgium, France, Italy, the Netherlands and Spain), many clinics, registries and national networks have developed heterogeneously in a number of countries. Six NMD reference centres are recognised in Belgium as offering multidisciplinary care at all stages of the disease. Italy’s network, consisting of thirty centres, focuses on registries, clinical trials, training and education. The Dutch neuromuscular research centre, ISNO, includes seven centres working closely with patient organisations. The Spanish network, RENEM, has prioritised patient data collection to harmonise healthcare planning and contribute towards research.

The workshop participants evaluated resources, opportunities and challenges to implement ERNs in the field of NMDs. In January 2013, the EUCERD Joint Action published recommendations on ERNs. Guidelines would be drawn up following the workshop, in accordance with these European health policy priorities on ERNs for rare diseases. Participants recommended establishing e-health tools and telemedicine to improve timely, seamless and cost-effective patient access to specialised health services. They acknowledged the central role of scientific societies to provide professional education and training. They also recognised the need to cover all NMD groups to avoid excluding patients with very rare NMDs.

It was agreed that all existing structures should be involved or incorporated into ERNs, including registries, biobanks, research teams, national and regional networks and patient organisations. Such multidisciplinary ERNs would be better equipped to improve patient diagnosis, deliver comprehensive care, measure and monitor health impact and outcomes, streamline and advance research, formulate guidelines and raise funds to ensure sustainability.

Consult the PubMed abstract

Report from the EUROPLAN UK National Conference on a strategy for rare diseases
The EUROPLAN National Conference on rare diseases in the UK took place on 24th June 2014 to assess the UK’s strategy for rare diseases and implementation of its four national plans. The conference report highlights recommendations and Rare Disease UK (RDUK) guidance to address rare diseases in all four nations, i.e. England, Scotland, Wales and Northern Ireland. In November 2013, health ministers from all four UK nations signed the UK Strategy for Rare Diseases outlining 51 commitments to address rare disorders.

The report recommends that Government Health Departments ensure UK-wide implementation of the UK Strategy commitments in order to improve equal access to health services and avoid wasting resources. Conference participants believe registries, centres of excellence, screening, research and training programmes should collaborate across UK nation borders, and beyond, to improve best practice guidelines, knowledge transfer and patient care. It was agreed the UK Government’s Rare Disease Forum will coordinate the four nations’ efforts to identify areas of joint action and implement the UK Strategy commitments.

The conference participants encouraged input from the Medical Research Council and Royal Colleges to fulfil the commitments. Stakeholder and patient engagement is also considered essential to improve cross border coordination and increase awareness of the UK Strategy implementation. RDUK is constituting a Patient Empowerment Group, composed of some thirty UK patient organisations, to participate in implementation talks. Furthermore, based on Wales’ experience, participants agreed that indicators should be introduced to monitor the progress of plans across the UK.

Further recommendations were made to increase collaborative research network flexibility within the UK and across borders in efforts to encourage translational research and improve treatments for rare diseases. Regulatory authorities and medicines’ evaluation organisations, such as the National Institute for Clinical Excellence (NICE), are advised to work together, along with patient organisations, industry and other stakeholders to improve access to orphan drugs. While specific to the UK, the recommendations are applicable to other European countries, as part of the EU strategy to improve cross border healthcare for rare disease patients.

Read the report

UK policymakers call for a separate evaluation framework for ultra-orphan medicinal products for very rare diseases
In the UK, ultra-orphan medicinal products are assessed by the National Institute for Clinical Excellence’s (NICE) highly-specialised technologies (HST) evaluation framework. In March 2014, the UK’s Bioindustry Association (BIA) published a survey report of the political views on this evaluation framework, prior to the NICE’s formal consultation on the evaluation process, due to take place by the end of 2014.

The BIA’s findings indicated that 68% of MPs agreed that access to treatment for very rare diseases should not be based solely on the UK’s National Health Service’s (NHS) capacity to pay, but rather on patient medical needs. Furthermore, 63% of PMs were not in favour of capping per capita funding to treat very rare and complex diseases. Half of MPs disagreed that a standard mathematical methodology is appropriate to assess medicines for very rare diseases.

The report suggests that policymakers believe a separate HST evaluation process should be implemented to take into consideration the data limitations of small patient populations. They consider that priority should be given to assessing clinical efficacy of ultra-orphan medicines rather than cost effectiveness.

Read the report

The first sixteen rare disease cohorts of the RaDiCo programme have been launched

RaDiCo, a programme financed by the French Ministry for Research, aims to generate data on rare disease phenotypes in efforts to contribute towards clinical studies and epidemiology. The rare disease cohort composition is coordinated with rare disease healthcare providers and depends largely on data contribution and patients from reference centres and centres of expertise. These cohorts will facilitate research on rare disease natural history, disease mechanisms, new therapeutic investigation opportunities and public health indicators. RaDiCo launched a call for projects in January 2014 and received 63 letters of intent. An international expert panel selected sixteen of those rare disease cohorts, listed below:

  • RaDiCo-AC-ŒIL: National cohort for improving ocular and extra-ocular outcome prediction in patients with congenital defects of the eye; coordinated by Patrick Calvas and Nicolas Chassaing.

  • RaDiCo-ACOStill: Adult and Childhood Onset Still disease Cohort; coordinated by Sophie Georgin-Lavialle.

  • RaDiCo-COBBALT: COhort for Bardet-Bield syndrome and ALsTröm syndrome; coordinateur by Hélène Dollfus.

  • RaDiCo-COLPAC: National Cohort on Low Phospholipid-Associated Cholelithiasis (LPAC) syndrome for new knowledge on the epidemiology, clinical and genetic heterogeneity of the disease; coordinateur by Christophe Corpechot.

  • RaDiCo-ECYSCO: European Cystinosis Cohort; coordinateur by Aude Servais.

  • RaDiCo-EURBIO Alport: Alport Syndrome: European cohort and database for the search of biomarkers able to predict the progression of the renal disease; coordinated by Laurence Heidet et Bertrand Knebelmann.

  • RaDiCo-FARD: National cohort for the evaluation and monitoring of individual overall, physical, mental, social and economic disability in the course of rare skin diseases; coordinated by Christine Bodemer.

  • RaDiCo-GenIDA: International social network and data collection on the natural history of rare monogenic forms of intellectual disabilities; coordinated by Jean-Louis Mandel.

  • RaDiCo-IDMet: National and European cohort on Imprinting Disorders and Metabolism Future; coordinated by Agnès Linglart et Irène Netchine.

  • RaDiCo-MARFAN: National cohort on Marfan syndrome and related diseases; coordinated by Guillaume Jondeau.

  • RaDiCo-MPS: Mucopolysaccharidosis patients in France in the era of specific therapeutics; coordinated by Bénédicte Héron.

  • RaDiCo-PCD: Primary Ciliary Dyskinesia (PCD) national cohort: Identification of severity criteria from deep phenotyping and phenotype-genotype correlation study; coordinated by Estelle Escudier.

  • RaDiCo-PP: National cohort on periodic paralysis for clinical, genetic and medico-economic studies; coordinated by Savine Vicart.

  • RaDiCo-RESPI: Idiopathic Interstitial Pneumonia French cohort study: Genetic and environmental determinants, from infancy to elderly; coordinated by Annick Clement.

  • RaDiCo-RETICO: Inherited retinal dystrophies cohort; coordinated by Hélène Dollfus.

  • RaDiCo-REVASC: ARterial Evolutivity In the course of VASCular Ehlers-Danlos national cohort study; coordinated by Xavier Jeunemaître.

  • For further information

    Rare diseases and access to orphan drugs in Latvia: a national plan but much progress needed
    In an article published in the Orphanet Journal of Rare Diseases, Logviss et al. describe the situation in Latvia in the field of rare diseases. While a Latvian national plan for rare diseases was approved in June 2013, progress has been slow to increase activity and improve research, treatment and education in rare diseases. Though research on rare diseases has not been given priority in Latvia, researchers and experts are conducting several projects and collaborations with Baltic States and other countries. No official centres of expertise for rare diseases have been designated and only one rare disease patient register is listed by Orphanet. Patient data are collected in several university hospitals and patient organisations. Adoption of the e-health project, planned in 2014, is expected to improve patient data collection into a centralised database and a pilot project plans to apply Orphacodes and OMIM codes to identify rare disease patients.

    The national screening programme covers two rare disorders only — phenylketonuria and congenital hypothyroidism — and the National Health Service finances a few additional prenatal and postnatal diagnostic tests, including those for metabolic disorders, spinal muscular atrophy, Huntington disease and fragile X syndrome. No national clinical guidelines have been approved and rehabilitation services for rare disease patients have decreased over the past years due to reduced state funding for such medical services.

    The Latvian Rare Disease Association Caladrius was launched in 2009, to provide information and support, represent and help finance treatments for rare disease patients. Other rare disease patient organisations collaborate with Caladrius and hope to constitute a national alliance of rare disease patient organisations. The Latvian State Agency of Medicines (SAM) decides on pricing and reimbursement of EMA approved orphan drugs registered in Latvia and is responsible for drug safety and evaluation. Out of 72 EMA approved orphan drugs available in the EU, 28 only are available in Latvia. Some orphan drugs have been included in compassionate use programmes, i.e. allowing the use of unauthorised medicines, in Latvian hospitals. Since Latvia has developed no specific pricing policy, Logviss et al. suggest that budget impact studies would help determine the cost of treating rare disease patients and contribute towards better planning for rare disease management.

    While the launch of the rare disease national plan is a step forward, the authors state that considerable efforts are still required to address the needs of rare disease patients in Latvia.

    Read the open access article

    Other International News
    The FDA has awarded fifteen grants to stimulate drug, device and biological product development

    On 30th September, the FDA announced it has awarded fifteen grants, representing over US$ 19 million, to foster the development of medical devices, drugs and biological products for patients with rare diseases. Around a quarter of the funding is directed towards research on paediatric rare diseases.

    Read the press announcement

    Guidance Documents and Recommendations
    Hemoglobinopathy: EMQN best practice guidelines for molecular and hematology methods for carrier identification and prenatal diagnosis
    Consult the Pubmed abstract
    To read more about "Hemoglobinopathy"

    Eur J Hum Genet. ; [Epub ahead of print] ; July 2014
    Sickle cell anemia: summary of the National Heart, Lung, and Blood Institute (NHLBI) 2014 guidelines for management
    Consult the Pubmed abstract
    To read more about "Sickle cell anemia"

    JAMA ; 312(10):1033-48 ; September 2014
    Fibrous dysplasia and McCune-Albright syndrome: imaging for positive and differential diagnoses, prognosis, and follow-up guidelines
    Consult the Pubmed abstract
    To read more about "Fibrous dysplasia of bone"
    To read more about "McCune-Albright syndrome"
    To read more about "Mazabraud syndrome"

    Eur J Radiol. ; 83(10):1828-42 ; October 2014
    Methylmalonic and propionic acidemia: guidelines for the diagnosis and management
    Consult the Pubmed abstract
    To read more about "Vitamin B12-unresponsive methylmalonic acidemia"
    To read more about "Vitamin B12-responsive methylmalonic acidemia"
    To read more about "Methylmalonic acidemia with homocystinuria"
    To read more about "Propionic acidemia"

    Orphanet J Rare Dis. ; 9(1):130 ; September 2014
    Bioinformatics, Registries and Data Management

    Automated search tools to retrieve published rare disease cases would improve patient identification and diagnosis
    As the number of published clinical case reports and literature on rare diseases increases, so does the need to develop automated tools to identify and analyse the literature. This is particularly relevant in the field of rare diseases, where practitioners rely frequently on manually retrieved case reports to support their diagnosis of patients with rare conditions. In an article published in Database, Taboada et al. propose their methods of identifying and annotating relevant case reports in efforts to improve phenotypic descriptions for rare disease diagnosis.

    Currently available tools, such as PubMed’s Medical Subject Headings (MeSH) standard terminology thesaurus, GoPubMed search engine based on the Gene Ontology (GO) and MeSH and SEGOPubmed, offer various methods of retrieving abstracts using key term searches. While MeSH and GO are the most frequently used tools, others such as the Open Biological and Biomedical Ontologies (OBO), the National Center of Biomedical Ontology (NCBO) bioportal and the Human Phenotype Ontolgy (HPO) are more suitably adapted to certain diseases.

    Taboada et al. suggest developing methods, using the various available tools, to facilitate automated and exhaustive extraction of reports on patients with phenotypic similarities. The authors propose techniques to generate semantic patient data indexing using linguistic patterns which can be further analysed. They believe their approach would contribute towards data curation for rare disease indexing and analysis.

    Read the open access article

    Rare disease research networks: the necessity and value of pooling resources to advance research on urea cycle disorders
    Researchers working on rare diseases are frequently aware of the necessity to pool knowledge and resources to advance research and therapeutic development for rare diseases. In an article published in Molecular Genetics and Metabolism, Summar et al. describe the success of collaborations between registries, researchers and patient organisations operating in the field of urea cycle disorders (UCD) and between three large international consortia.

    Researchers, institutes and patient organisations have developed consortia in the United States, Europe and Japan to optimise their resources, in response to the lack of data, knowledge gaps and inadequate treatment guidelines on urea cycle disorders. The NIH’s Urea Cycle Disorders Consortium (UCDC) has enrolled 680 eligible patients in a longitudinal study and has developed seven clinical protocols. The EU-funded European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD) has enrolled 417 patients with UCD, and the Japanese UCD Consortium (JUCDC) has enrolled over 200 patients.

    The three consortia have also developed alliances among themselves through bi- and trilateral memberships to share knowledge and data. The authors highlight that, while the three consortia were launched several years apart, they have successfully built strong partnerships. Summar et al. suggest their success stems from four factors: cooperation, rather than competition, and human interaction; patient contribution; collaboration and credit sharing; and a respected and strong administration. The authors believe this example of collaboration on UCD illustrates how pooling resources helps overcome certain limitations of research on rare diseases. Research consortia are able to reach larger patient numbers, benefit from greater resources to explore and compare different therapeutic options and create opportunities to generate new ideas and projects.

    Consult the abstract

    The opportunities and technical challenges of sharing genomic data for research and diagnosis of genetic and rare disorders
    Rapid advances in sequencing technologies are constantly contributing towards improving clinical diagnostic powers to identify and treat genetic disorders and rare diseases appropriately. In an article published in Genome Medicine, Robinson describes the potential benefits but also the challenges of sharing and exploiting data generated by genomics technologies. The author highlights the technical barriers to store and share vast datasets using currently available bioinformatics tools.

    Robinson indicates that databases such as ClinVar, DECIPHER and PhenomeCentral allow researchers to search, share and store genetic data for research on rare diseases. Other recent projects were initiated to standardise data collection and facilitate data sharing, such as the Human Genome Variation Society (HGVS) and the Human Variome Project (HVP). While data repositories are useful to access individual datasets, users are invariably unable to access multiple datasets from different sources.

    The author describes NGS-Logistics software as a potential solution for researchers to retrieve and share large datasets from multiple data centres. If installed in each data centre, NGS-Logistics software can locate data in different centres according to searched genes or variants. Robinson suggests that NGS-Logistics could help researchers engage in collaborative efforts to share data and accelerate therapeutic development.

    Read the open access article

    Screening and Testing

    Report from the international workshop on biomarkers in Duchenne Muscular Dystrophy

    The 204th European Neuro Muscular Centre (ENMC) workshop on biomarkers aimed to increase international collaboration and harmonisation on research programmes in the field of biomarker discovery and development for use in the field of rare diseases. Biomarkers are used to evaluate disease progression — particularly relevant to chronic and progressive rare diseases — and the effect of drugs on disease evolution during clinical trials. In the workshop report published in Neuromuscular Disorders, Ferlini et al. highlight the recent progress made on biomarker research in Duchenne muscular dystrophy (DMD), illustrating current international collaborative efforts. The multidisciplinary participants acknowledged the need to further pool resources to increase patient data and biological sample collection in order to validate clinical findings.

    Presentations were given from the research, industrial and regulatory points of view to highlight biomarker uses. Participants expressed the necessity to develop guidelines to harmonise and regulate biomarker interpretation and application in order to satisfy product registration requirements. Patient organisations emphasised the need for patient and parent education and professional training to understand the role of biomarkers in DMD therapeutic investigations. DMD registry representatives highlighted the importance of developing standard operating procedures (SOP) to collect patient data and biological samples. Innovative technologies to develop biomarkers were presented to illustrate methods adapted to DMD.

    Participants agreed on the need to develop further collaborative programmes to share data between US and EU projects in order to optimise data and method exploitation for biomarker identification and validation. The authors report that lists of biomarkers for DMD will be drawn up and a DMD biomarker database should be set up. Finally, discussions will be conducted with regulatory bodies to establish biomarker regulation.

    Consult the abstract


    New Syndromes

    New syndrome with retinitis pigmentosa is caused by nonsense mutations in RDH11 in three siblings
    The authors investigated three siblings, born to asymptomatic parents, who each presented with atypical retinitis pigmentosa (RP) with systemic features, including facial dysmorphologies, psychomotor developmental delays recognized since early childhood, learning disabilities and short stature. RP-associated ophthalmological findings included salt-and-pepper retinopathy, attenuation of the arterioles and generalized rod–cone dysfunction. Atypical for RP features included mottled macula at an early age and peripapillary sparing of the retinal pigment epithelium. Whole-exome sequencing data identified compound heterozygous stop mutations in the RDH11 gene.
    Consult the Pubmed abstract

    Hum Mol Genet. ; 23(21):5774-80 ; November 2014
    Familial syndrome of conduction system disease, atrial tachyarrhythmia and dilated cardiomyopathy due to TNNI3K mutation
    The authors identified a familial syndrome of atrial tachyarrhythmia, conduction system disease, and dilated cardiomyopathy vulnerability. Seven members of a three-generation family exhibited the variably expressed phenotype. An unreported heterozygous missense mutation was found in TNNI3K.
    Consult the Pubmed abstract

    Hum Mol Genet. ; 23(21):5793-804 ; November 2014
    Hypomyelination with spinal muscular atrophy and cerebellar hypoplasia caused by EXOSC8 mutations
    The authors showed that homozygous missense mutations in EXOSC8 caused progressive and lethal neurological disease in 22 infants from three independent pedigrees. Affected individuals presented cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system or spinal motor neuron disease.
    Consult the Pubmed abstract

    Nat Commun. ; 5:4287 ; July 2014
    A human immunodeficiency reminiscent of APDS caused by heterozygous mutations in the PIK3R1 gene
    The authors identified heterozygous mutations in PIK3R1 in four patients from three unrelated families diagnosed with hypogammaglobulinemia and recurrent infections. The immunological phenotype of these patients was heterogeneous and reminiscent of that observed in activated PIK3-delta syndrome (APDS). Various defects in the PI3K-triggered pathway could cause primary immunodeficiencies.
    Consult the Pubmed abstract

    J Clin Invest. ; 124(9):3923-8 ; September 2014
    Novel syndrome of primordial dwarfism linked to NSMCE2 heterozygous frameshift mutations in two patients
    The authors characterized two patients with primordial dwarfism, extreme insulin resistance, and gonadal failure. They identified compound heterozygous frameshift mutations in NSMCE2.
    Consult the Pubmed abstract

    J Clin Invest. ; 124(9):4028-38 ; September 2014
    A new inborn error of metabolism affecting valine metabolism: ECHS1 mutations in Leigh disease
    Two siblings with fatal Leigh disease had increased excretion of S-(2-carboxypropyl) cysteine and several other metabolites. In contrast to neurodegeneration due to 3-hydroxyisobutyryl-CoA hydrolase deficiency (HIBCH deficiency), the excretion of 3-hydroxyisobutyryl-carnitine was normal in the children, suggesting deficiency of short chain enoyl-CoA hydratase (ECHS1 gene). Both children presented compound heterozygous mutations in ECHS1.
    Consult the Pubmed abstract

    Brain ; [Epub ahead of print] ; August 2014
    Patients with cataracts, growth hormone deficiency with short stature, partial sensorineural deafness and peripheral neuropathy or with Leigh syndrome present an IARS2 mutation
    The authors reported a novel disorder in three adult patients with a phenotype including cataracts, short stature secondary to growth hormone deficiency, sensorineural hearing deficit, peripheral sensory neuropathy and skeletal dysplasia. They identified identified a homozygous missense mutation in IARS2 in affected patients. Compound heterozygous mutations in IARS2 were independently identified in a previously unreported patient with a more severe mitochondrial phenotype diagnosed as Leigh syndrome.
    Consult the Pubmed abstract

    Hum Mutat. ; [Epub ahead of print] ; August 2014
    A hereditary bleeding disorder resulting from a premature stop codon in thrombomodulin
    The authors identified three members of a family with a history of post-traumatic bleeding to be heterozygous for a novel thrombomodulin (THBD) mutation.
    Consult the Pubmed abstract

    Blood ; 124(12):1951-6 ; September 2014
    A severe skeletal dysplasia resulting from a novel dominant COL11A1 mutation in a family
    The authors described a family with a severe skeletal dysplasia caused by a novel dominantly inherited COL11A1 mutation. Two siblings each presented with severe myopia, hearing loss, micromelia, metaphyseal widening of the long bones, micrognathia, and airway compromise requiring tracheostomy. Both died in early childhood because of tracheostomy dislodging or plugging. Their mother had mild rhizomelic shortening of the limbs, brachydactyly, and severe myopia; she was found mosaic for the COL11A1 mutation.
    Consult the Pubmed abstract

    Am J Med Genet A. ; 164(10):2607-12 ; October 2014
    Epithelial inflammation resulting from an inherited loss-of-function mutation in EGFR
    The authors identified a homozygous loss-of-function missense mutation in EGFR in a male infant with lifelong inflammation affecting the skin, bowel, and lungs. During the first year of life, his skin showed erosions, dry scale, and alopecia. Subsequently, there were numerous papules and pustules similar to the rash seen in patients receiving EGFR inhibitor drugs. The boy died at the age of 2.5 years from extensive skin and chest infections as well as electrolyte imbalance.
    Consult the Pubmed abstract

    J Invest Dermatol. ; 134(10):2570-8 ; October 2014
    Severe developmental delay in a boy and a girl due to de novo missense mutations in the NAA10 gene
    The authors identified de novo missense variants in NAA10 in two unrelated individuals, a boy and a girl, with severe global developmental delay and growth retardation but without any major dysmorphism.
    Consult the Pubmed abstract

    Eur J Hum Genet. ; [Epub ahead of print] ; August 2014

    New Genes

    Amelogenesis imperfecta is associated with deletion of AMBN exon 6
    Consult the Pubmed abstract
    To read more about "Hypoplastic amelogenesis imperfecta"
    To read more about "Amelogenesis imperfecta"

    Hum Mol Genet. ; 23(20):5317-24 ; October 2014
    Spectrum of neuromuscular clinical manifestations due to POMK mutations which disrupt muscle development
    Consult the Pubmed abstract
    To read more about "Limb-girdle muscular dystrophy"

    Hum Mol Genet. ; 23(21):5781-92 ; November 2014
    Spinocerebellar ataxia type 21: TMEM240 is at cause and should be tested in cases with mild or slowly progressive ataxia, particularly with moderate to severe cognitive impairment
    Consult the Pubmed abstract
    To read more about "Spinocerebellar ataxia type 21"

    Brain ; 137(Pt 10):2657-63 ; October 2014
    Familial neurofibromatosis type 3 is associated with a germline missense mutation in COQ6
    Consult the Pubmed abstract
    To read more about "Neurofibromatosis type 3"

    Genet Med. ; 16(10):787-792 ; October 2014
    Steel syndrome: a recessive osteochondrodysplasia caused by a COL27A1 variant suggested to be a founder mutation in the Puerto Rican population
    Consult the Pubmed abstract
    Eur J Hum Genet. ; [Epub ahead of print] ; July 2014
    Acroscyphodysplasia as a phenotypic variation of pseudohypoparathyroidism and acrodysostosis type 2 linked to either a GNAS or a PDE4D mutation
    Consult the Pubmed abstract
    To read more about "Metaphyseal acroscyphodysplasia"

    Am J Med Genet A. ; 164(10):2529-34 ; October 2014
    Juvenile Paget disease can be associated with an activating heterozygous duplication within TNFRSF11A
    Consult the Pubmed abstract
    To read more about "Juvenile Paget disease"

    Bone ; 68:153-61 ; November 2014
    Severe syndromic retinal ciliopathy caused by POC1B mutation
    Consult the Pubmed abstract
    Hum Mutat. ; 35(10):1153-62 ; October 2014
    Cone rod dystrophy due to homozygous missense variant in CNGA3 in a large consanguineous Pakistani family
    Consult the Pubmed abstract
    To read more about "Cone rod dystrophy"

    Eur J Hum Genet. ; [Epub ahead of print] ; July 2014
    A vacuolar myopathy with accumulation of sarcoplasmic reticulum protein aggregates caused by a mutation in the CASQ1 gene
    Consult the Pubmed abstract
    To read more about "Myopathy due to calsequestrin and SERCA1 protein overload"

    Hum Mutat. ; 35(10):1163-70 ; October 2014
    Disseminated superficial actinic porokeratosis associated with SLC17A9 missense variants in two Chinese pedigrees
    Consult the Pubmed abstract
    To read more about "Disseminated superficial actinic porokeratosis"

    J Med Genet. ; 51(10):699-704 ; October 2014
    Intractable seizures and evidence of defective endocytotic trafficking linked to a homozygous missense mutation in ZFYVE20 in a female
    Consult the Pubmed abstract
    Orphanet J Rare Dis. ; 9(1):141 ; September 2014
    Evidence against RAB40AL being the locus for Martin-Probst deafness-intellectual disability, as high prevalence of the variant is typical for a common genetic variation
    Consult the Pubmed abstract
    To read more about "Deafness - intellectual disability, Martin-Probst type"

    Hum Mutat. ; 35(10):1171-4 ; October 2014

    Research in Action

    Clinical Research
    Duchenne muscular dystrophy: safety and efficacy of drisapersen (a 2’-O-methyl-phosphorothioate antisense oligonucleotide) for treatment
    Consult the Pubmed abstract

    To read more about "Duchenne muscular dystrophy"

    Lancet Neurol. ; 13(10):987-96 ; October 2014
    Neurofibromatosis type 1: short-term benefit of methylphenidate on attention deficit hyperactivity-like disorder in children
    Consult the Pubmed abstract
    Consult this study on Orphanet

    To read more about "Neurofibromatosis type 1"

    Orphanet J Rare Dis. ; 9(1):142 ; September 2014
    Metastatic renal cell carcinoma: trial results support the standard treatment paradigm of first-line sunitinib followed by everolimus at progression
    Consult the Pubmed abstract
    Consult this study on Orphanet

    To read more about "Non-familial renal cell carcinoma"

    J Clin Oncol. ; 32(25):2765-72 ; September 2014
    Mucopolysaccharidosis type 2: idursulfase administration may result efficacious in delaying the somatic disease progression but did not improve several signs and symptoms
    Consult the Pubmed abstract

    To read more about "Mucopolysaccharidosis type 2"

    Orphanet J Rare Dis. ; 9(1):129 ; September 2014
    Glioblastoma: gene therapy to confer O6-benzylguanine resistance in hematopoietic stem cells enhances chemotherapy tolerance and efficacy in patients
    Consult the Pubmed abstract
    J Clin Invest. ; 124(9):4082-92 ; September 2014
    Corticosteroid-resistant autoimmune inner ear disease: early efficacy trial of anakinra
    Consult the Pubmed abstract
    J Clin Invest. ; 124(9):4115-22 ; September 2014
    Cerebellar ataxia with glutamic acid decarboxylase antibodies: subacute onset of symptoms and prompt immunotherapy are associated with good outcome
    Consult the Pubmed abstract
    JAMA Neurol. ; 71(8):1009-16 ; August 2014
    Malignant migrating partial seizures of infancy: quinidine treatment in a child with activating mutation in KCNT1 reduced seizure frequency and improved psychomotor development
    Consult the Pubmed abstract
    To read more about "Malignant migrating partial seizures of infancy"

    Ann Neurol. ; 76(3):457-61 ; September 2014
    Atypical hemolytic-uremic syndrome: C5b-9 endothelial deposits might help monitor eculizumab effectiveness, avoid drug overexposure, and save money
    Consult the Pubmed abstract
    To read more about "Atypical hemolytic-uremic syndrome"

    Blood ; 124(11):1715-26 ; September 2014
    Acute heart failure attributable to rupture of the mitral chordae tendineae should be recognised as a significant cardiovascular disorder in infants
    Consult the Pubmed abstract
    Circulation ; 130(13):1053-61 ; September 2014
    Rasopathy with clinical features overlapping Noonan and cardiofaciocutaneous syndromes caused by a novel SHOC2 variant
    Consult the Pubmed abstract
    To read more about "Noonan syndrome"
    To read more about "Cardiofaciocutaneous syndrome"
    To read more about "Noonan syndrome-like disorder with loose anagen hair"

    Hum Mutat. ; [Epub ahead of print] ; August 2014
    Therapeutic Approaches

    Diseases characterized by defects in the neuromuscular junction: DOK7 gene therapy benefits mouse models
    Consult the Pubmed abstract
    To read more about "Congenital myasthenic syndrome"
    To read more about "Emery-Dreifuss muscular dystrophy"
    To read more about "Postsynaptic congenital myasthenic syndromes"

    Science ; 345(6203):1505-8 ; September 2014
    Collagen VI congenital muscular dystrophy: NIM811, a cylophilin inhibitor without immunosuppressive activity, is beneficial in different models
    Consult the Pubmed abstract
    To read more about "Bethlem myopathy"
    To read more about "Congenital muscular dystrophy, Ullrich type"

    Hum Mol Genet. ; 23(20):5353-63 ; October 2014
    Autosomal recessive limb-girdle muscular dystrophy type 2F: use of a p38MAPK pharmacologic inhibitor reduced dystrophic disease in a mouse model
    Consult the Pubmed abstract
    To read more about "Autosomal recessive limb-girdle muscular dystrophy type 2F"

    Hum Mol Genet. ; 23(20):5452-63 ; October 2014
    Distal myopathy, Nonaka type: sialyllactose ameliorates myopathic phenotypes in symptomatic model mice
    Consult the Pubmed abstract
    To read more about "Distal myopathy, Nonaka type"

    Brain ; 137(Pt 10):2670-9 ; October 2014
    X-linked agammaglobulinemia: splice-correcting oligonucleotides restore BTK function in model mice
    Consult the Pubmed abstract
    To read more about "X-linked agammaglobulinemia"

    J Clin Invest. ; 124(9):4067-81 ; September 2014
    Familial platelet syndrome with predisposition to acute myelogenous leukemia: correction of RUNX1 mutation through gene targeting led to normalization of megakaryopoiesis
    Consult the Pubmed abstract
    To read more about "Familial platelet syndrome with predisposition to acute myelogenous leukemia"

    Blood ; [Epub ahead of print] ; August 2014
    22q11.2 deletion syndrome: pharmacologic inhibition of p53 partially rescues the mutant phenotype in mouse embryonic model
    Consult the Pubmed abstract
    To read more about "22q11.2 deletion syndrome"

    Proc Natl Acad Sci U S A. ; 111(37):13385-90 ; September 2014
    Short bowel syndrome: glucagon-like peptide-2 therapy improves outcomes of intestinal adaptation in a distal-intestinal resection neonatal piglet model
    Consult the Pubmed abstract
    To read more about "Congenital short bowel syndrome"

    Pediatr Res. ; 76(4):370-7 ; October 2014
    Inhibition of metalloprotease hyperactivity in cystic cholangiocytes halts the development of polycystic liver diseases
    Consult the Pubmed abstract
    To read more about "Isolated polycystic liver disease"
    To read more about "Autosomal recessive polycystic kidney disease"

    Gut ; 63(10):1658-67 ; October 2014
    Pancreatic carcinoma: identification of a new class of MDM2 inhibitor that led to regression of orthotopic tumors in mice
    Consult the Pubmed abstract
    To read more about "Pancreatic carcinoma"

    Gastroenterology ; 147(4):893-902.e2 ; October 2014
    Graft versus host disease: prophylactic extracorporeal photopheresis may provide an alternative and safe method for immunosuppression in the bone marrow transplant setting
    Consult the Pubmed abstract
    To read more about "Graft versus host disease"
    To read more about "Acute graft versus host disease"

    Blood ; 124(11):1832-42 ; September 2014
    Ebola hemorrhagic fever: chimpanzee-derived replication defective adenovirus vaccine boosted with modified Ankara virus generates acute and durable protective immunity in macaques
    Consult the Pubmed abstract
    To read more about "Ebola hemorrhagic fever"

    Nat Med. ; 20(10):1126-1129 ; October 2014
    Diagnostic Approaches

    Amyloidosis: review on diagnosis
    Consult the Pubmed abstract
    To read more about "Amyloidosis"

    Intern Med J. ; 44(1):7-17 ; January 2014
    Wiskott-Aldrich syndrome: newborn screening for severe T and B cell lymphopenia identifies a fraction of patients
    Consult the Pubmed abstract
    To read more about "Wiskott-Aldrich syndrome"

    Clin Immunol. ; 155(1):74-78 ; September 2014

    Patient Management and Therapy
    Ehlers-Danlos syndrome, vascular type: review on pregnancy-related deaths and complications in women
    Consult the Pubmed abstract
    To read more about "Ehlers-Danlos syndrome, vascular type"

    Genet Med. ; [Epub ahead of print] ; June 2014
    Myasthenia gravis: increased risk of osteoporosis in patients
    Consult the Pubmed abstract
    To read more about "Myasthenia gravis"

    Neurology ; 83(12):1075-9 ; September 2014
    Noonan syndrome: all children should be systematically evaluated for clinical signs of myeloproliferative disorders and basic hematological parameters
    Consult the Pubmed abstract
    To read more about "Noonan syndrome"

    J Med Genet. ; 51(10):689-97 ; October 2014
    Behçet disease with Budd-Chiari syndrome: early management with immunosuppressive and anticoagulation therapy is the best treatment for patients
    Consult the Pubmed abstract
    To read more about "Budd-Chiari syndrome"
    To read more about "Behçet disease"

    Orphanet J Rare Dis. ; 9(1):104 ; September 2014
    Report on the 199th ENMC international workshop on FHL1 related myopathies
    Consult the Pubmed abstract
    To read more about "Reducing body myopathy"
    To read more about "X-linked myopathy with postural muscle atrophy"
    To read more about "X-linked Emery-Dreifuss muscular dystrophy"
    To read more about "Familial isolated hypertrophic cardiomyopathy"

    Neuromuscul Disord. ; 24(5):453-62 ; May 2014
    Report on the 197th ENMC international workshop on neuromuscular disorders of mitochondrial fusion and fission
    Consult the abstract
    To read more about "Autosomal dominant optic atrophy, classic type"
    To read more about "Autosomal dominant optic atrophy plus syndrome"
    To read more about "Autosomal dominant Charcot-Marie-Tooth disease type 2A2"
    To read more about "Hereditary motor and sensory neuropathy type 6"
    To read more about "Severe early-onset axonal neuropathy due to MFN2 deficiency"

    Neuromuscul Disord. ; 24(8):736-42 ; August 2014
    Fabry disease and other lysosomal storage disorders: a review
    Consult the abstract
    To read more about "Fabry disease"
    To read more about "Glycogen storage disease due to LAMP-2 deficiency"
    To read more about "Glycogen storage disease due to acid maltase deficiency"

    Circulation ; 130(13):1081-90 ; September 2014
    Graft versus host disease: review on current and emerging strategies for the prevention
    Consult the abstract
    To read more about "Graft versus host disease"

    Nat Rev Clin Oncol. ; 11(9):536-47 ; September 2014
    Retinoblastoma: review on targeted management
    Consult the abstract
    To read more about "Retinoblastoma"

    Curr Opin Ophthalmol. ; 25(5):374-85 ; September 2014
    Pancreatic carcinoma: a review
    Consult the abstract
    To read more about "Pancreatic carcinoma"

    N Engl J Med. ; 371(11):1039-49 ; September 2014
    Sinonasal carcinoma: review on clinical, pathological, genetic and therapeutic advances
    Consult the abstract
    Nat Rev Clin Oncol. ; 11(8):460-72 ; August 2014
    Disorder of sex development: two reviews on management and genetics
    Consult the abstracts
    To read more about "Disorder of sex development"

    Nat Rev Endocrinol. ; 10(9):520-9 ; September 2014
    Nat Rev Endocrinol. ; 10(10):603-615 ; October 2014
    Chronic acquired demyelinating polyneuropathies: review on diagnosis and treatment
    Consult the abstract
    To read more about "Chronic inflammatory demyelinating polyneuropathy"
    To read more about "Lewis-Sumner syndrome"
    To read more about "Polyneuropathy associated with IgM monoclonal gammapathy with anti-MAG"
    To read more about "Multifocal motor neuropathy"
    To read more about "POEMS syndrome"

    Nat Rev Neurol. ; 10(8):435-46 ; August 2014
    Guillain-Barré syndrome: two reviews on pathogenesis, diagnosis, treatment and prognosis
    Consult the Pubmed abstracts
    To read more about "Guillain-Barré syndrome"
    To read more about "Miller-Fisher syndrome"

    Nat Rev Neurol. ; 10(8):469-82 ; August 2014
    Nat Rev Neurol. ; 10(9):537-44 ; September 2014
    Complex regional pain syndromes: review on treatment
    Consult the Pubmed abstract
    To read more about "Complex regional pain syndrome"
    To read more about "Complex regional pain syndrome type 1"
    To read more about "Complex regional pain syndrome type 2"

    Nat Rev Neurol. ; 10(9):518-28 ; September 2014
    Neuromyelitis optica: two reviews on prevalence, pathogenesis and treatment
    Consult the Pubmed abstracts
    To read more about "Neuromyelitis optica"

    Nat Rev Neurol. ; 10(9):493-506 ; September 2014
    Nat Rev Neurol. ; 10(9):529-36 ; September 2014
    ANCA-associated vasculitis: two reviews on key advances
    Consult the Pubmed abstracts
    To read more about "Eosinophilic granulomatosis with polyangiitis"
    To read more about "Microscopic polyangiitis"
    To read more about "Granulomatosis with polyangiitis"

    Nat Rev Rheumatol. ; 10(8):484-93 ; August 2014
    Nat Rev Rheumatol. ; 10(8):494-501 ; August 2014
    Simpson-Golabi-Behmel syndrome types I and II: a review
    Lire le résumé
    To read more about "Simpson-Golabi-Behmel syndrome"
    To read more about "Simpson-Golabi-Behmel syndrome type 2"

    Orphanet J Rare Dis. ; 9(1):138 ; September 2014
    Legionellosis: review on epidemiology and clinical management
    Consult the Pubmed abstract
    To read more about "Legionellosis"

    Lancet Infect Dis. ; 14(10):1011-1021 ; October 2014
    Goldenhar syndrome: a review
    Consult the Pubmed abstract
    To read more about "Goldenhar syndrome"

    J Med Genet. ; 51(10):635-645 ; October 2014
    Ectodermal dysplasias: a special section in the October issue of the American Journal of Medical Genetics
    Consult the special issue
    American Journal of Medical Genetics ; 164A(10):2415-2489 ; October 2014
    One new and one updated Clinical Utility Gene Card published in the European Journal of Human Genetics
    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 one new Clinical Utility Gene Card for:
    X-linked immunodeficiency with magnesium defect, Epstein-Barr virus infection and neoplasia (XMEN)

    The European Journal of Human Genetics has published one updated Clinical Utility Gene Cards for:
    Aarskog–Scott Syndrome (faciogenital dysplasia)

    Ten 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. Ten updated GeneReviews have been published for:
    NDP-related retinopathies
    Nemaline myopathy
    PINK1 type of young-onset Parkinson disease
    Autoimmune lymphoproliferative syndrome
    Dystonia/Parkinsonism, hypermanganesemia, polycythemia, and chronic liver disease
    Shwachman-Diamond syndrome
    Stickler syndrome
    Urea cycle disorders
    Very long-chain acyl-coenzyme A dehydrogenase deficiency


    Orphan Drugs

    Political and Scientific News
    Orphan drug reimbursement in Belgium: assessing official and non-official decision criteria
    While most orphan drugs would not satisfy standard cost-effectiveness criteria to justify their high prices, many of them are systematically reimbursed. In an article published in Orphanet Journal of Rare Diseases, Picavet et al. describe the situation in Belgium, suggesting that a number of non-official factors influence the orphan drug reimbursement evaluation process. The Belgian Drug Reimbursement Committee (DRC) is responsible for evaluating applications for orphan drug reimbursement and the assessment process is based on five official criteria: therapeutic value, price, level of reimbursement, clinical significance and budgetary impact.

    Based on interviews, the authors collected evidence of how official and non-official factors may influence the decision making process for orphan drug reimbursement. Because no cost-effectiveness studies are required, the DRC has no pharmaco-economic data to support reimbursement decisions. The DRC, however, does carefully examine the budget impact analysis to help formulate a decision. While age and disease burden are integrated into reimbursement decisions, some cases are sometimes treated exceptionally, such as children with life threatening diseases. Orphan drugs are often attributed unofficial prices that are not communicated in order to avoid parallel trading.

    Other factors that may influence reimbursement decisions include the role of patient organisations. While they are not officially consulted during the decision making process, they create disease awareness which may influence opinions on the drug’s benefits. Similarly, expert opinions are not formally part of the reimbursement decision process, but may be included in the drug assessment. Further factors such as media influence, industry and government investment for research, ethical considerations and changing political climates could all have an impact on orphan drug reimbursement decisions.

    Picavet et al. believe that greater transparency of reimbursement criteria is needed to hold the DRC members more accountable for reimbursement decisions. A multi-criteria decision analysis (MCDA) has been proposed to integrate a larger range of official factors to evaluate orphan drugs in Belgium. The authors suggest the different criteria could be weighted according to their societal value. While they should be included, the authors recognise, nonetheless, that certain criteria are not easily quantifiable and could interact with each other.

    Read the open access article

    Mitigating adverse effects of orphan drugs despite challenges to conduct clinical trials on rare diseases
    Orphan drugs to treat rare and often life threatening diseases are authorised based on results from clinical trials in invariably limited patient numbers and accelerated approval procedures. Furthermore, the FDA recommends no population number thresholds for clinical trial safety studies for orphan drugs. In an article published in Expert Opinion on Orphan Drugs, O’Connell and Pariser compare and assess pre-market safety evaluation processes for rare and common disease drugs.

    The authors indicate that patient numbers in common disease drug safety trials are nine times greater than numbers included in orphan drug studies. In efforts to mitigate the higher risk uncertainty associated with orphan drug use, the FDA requires orphan drug developers to satisfy Risk Evaluation and Mitigation Strategy (REMS) programmes that include elements to assure safe use (ETASU) before or after drug approval. REMS ETASU programmes cannot, however, replace pre-market drug safety evaluation studies nor should they delay patient access to orphan drugs.

    O’Connell and Pariser highlight the challenges to assess orphan drug risk and safety profiles, since they are invariably based on incomplete and sparse data. The authors observed that safety labels for orphan drugs rarely required modifications following post market safety evaluations. They believe, therefore, that higher proportions (in terms of disease prevalence) of patients in orphan drug clinical trials than in common disease drug trials may compensate for the lack of pre-market data available for orphan drug evaluation.

    Rare disease patients, their families and physicians often tolerate higher risk uncertainty concerning orphan drug use, because an alternative is usually unavailable. Nevertheless, the authors believe that orphan drugs are generally and should systematically be assessed according to rigorous safety evaluation procedures. They recommend that orphan drug developers and regulatory agencies apply all necessary and appropriate methods to obtain a maximum amount of orphan drug safety data without impeding on patient access to these treatments.

    Consult the abstract

    Chemical drugs could be an alternative to gene therapy to treat certain genetic diseases
    In addition or as an alternative to gene therapy, chemical drugs could offer benefits to treat certain genetic disorders resulting from loss-of-function (LOF) or gain-of-function (GOF) mutations. In an article published in Drug Discovery Today, Sun et al. found that most chemical drug binding sites are located far from the gene mutation locus. Based on this assumption, the authors suggest that chemical drugs could target certain genetic disorders without the gene mutation interfering with the drug binding site.

    Over a hundred drug target pairs were matched with drug indications and genetic disease traits by comparing drug targets registered in the Therapeutic Target Database and genes registered in OMIM. These drug targets were studied to assess the influence of genetic mutations on candidate chemical drugs. The authors indicate that most of the studied genetic mutations had little influence on the drug binding sites. They suggest therefore that more chemical drugs should be considered as candidates to treat genetic and rare diseases.

    Consult the PubMed abstract

    The need to push beyond Normal Science to advance research on rare diseases
    In an editorial published in Expert Opinion on Orphan Drugs, Teagarden describes how progress in rare disease research depends largely on overcoming established scientific patterns and research approaches, otherwise known as Normal Science. In 1962, the Kuhn Cycle challenged the concept of Normal Science, which evolves progressively based on the accumulation of news ideas. His theory gave rise to the term 'paradigm shift', invariably used to describe disruptions in scientific research approaches.

    Teagarden illustrates how research on rare diseases depends on paradigm shifts to succeed. In the field of rare diseases, research breakthroughs have often resulted from patient organisation and parents’ perseverance to find a treatment for rare disease patients. The author suggests such actors need training to challenge and overcome Normal Science, attract more funds to initiate research programmes and identify potential roadblocks in research projects. With adequate training, advocacy groups could act as linchpins to dissolve resistance to innovation and scientific breakthroughs in rare disease research.

    Consult the abstract



    Collagen VI Alliance Call for Projects 2015
    A new international alliance has been established by AFM-Téléthon, the Muscular Dystrophy Campaign, Muscular Dystrophy Ireland, Cure CMD and the Swiss Foundation for Research on Muscle Diseases to fund research into collagen VI deficiencies that will further the development of therapeutic approaches and/or demonstrate a strong translational impact in this research field. In order to drive the development of treatments for these conditions forward, AFM-Téléthon and the Muscular Dystrophy Campaign have joined forces to launch a Call for Projects dedicated to collagen VI deficiencies with a particular focus on Ullrich muscular dystrophy and Bethlem myopathy.
    The research will be funded by the members of the Collagen VI Alliance. The call will be coordinated by the Muscular Dystrophy Campaign.

    Application deadline: 20 November, 2014

    For further details


    News from the Patients' Associations

    EURORDIS has launched a call for its 2015 Awards nominations
    EURORDIS has announced the fourth edition of its Awards for outstanding accomplishments, distinction and leading work in the field of rare diseases. The EURORDIS Awards recognise the significant contributions from patient advocacy groups, volunteers, companies and policymakers towards reducing the burden of rare diseases on people's lives.

    For further information

    EURORDIS campaign for European Year for Rare Diseases 2019
    In 2019, EURORDIS will celebrate the 20th anniversary of the EU Regulation on Orphan Medicinal Products adoption and the 10th anniversary of the Commission Communication and Council Recommendation on rare diseases. The European Year will send a strong public and political message on behalf of the 30 million Europeans affected by rare diseases and aims to raise awareness and draw researchers’ attention on these rare, mostly unknown, seriously debilitating and often life-threatening diseases.

    For further information


    Courses & Educational Initiatives

    Workshop: a common vocabulary to classify resources in the life science domain
    Date: 16 October, 2014
    Venue: Brussels, Belgium

    A one day vocabulary workshop, organised by ELIXIR, BioMedBridges and RDA, to agree on common vocabulary to classify resources in the life sciences domain. The course welcomes representatives of societies, networks, institutes, organisations, research infrastructures and projects and will involve and welcome ontologists to participate in discussions.
    For further information

    Genodermatoses Network Training Session
    Date: 30-31 October 2014
    Venue: Paris, France

    The objective of this course is to increase knowledge on cutis laxa, ectodermal and keratodermal disorders, their detection, diagnosis and management; develop and improve skills to manage common problems in different genodermatoses; encourage health care providers to adopt a multidisciplinary approach; provide updates on latest findings and treatments; highlight the key role of patient groups; and network specialists. This training is intended for all health care providers involved in the field of rare skin diseases.
    For further information

    III International EPIRARE workshop: rare disease and orphan drug registries
    Date: 24-25 November, 2014
    Venue: Rome, Italy

    Participants will be able to exchange experiences and present scientific results, in an effort to foster international collaboration.
    For further information

    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


    What's on Where?

    Dysmorphology and Radiology of Inborn Errors of Metabolism
    Date: 16-17 October, 2014
    Venue: Manchester, UK

    The topics covered will be of interest to clinicians who deal with rare disorders or have an interest in clinical genetics, IEMs or paediatrics. Participants are expected to have some background knowledge of the field, although extensive experience is not required. Participants are strongly recommended to bring interesting, unusual or unsolved cases for discussion.
    For further information

    II International Conference on Rare Cardiovascular Diseases
    Date: 16-17 October, 2014
    Venue: Krakow, Poland

    Under the Development of the European Network in Orphan Cardiovascular Diseases framework, co-funded by the Malopolska Regional Operational Programme, the conference is aimed at general physicians and experts treating patients with rare cardiovascular diseases. Discussions will also cover the healthcare system organisation for this group of patients. The conference is aimed at strengthening awareness on the need to coordinate research, disease registries and knowledge exchange to improve care for patients with rare cardiovascular diseases.
    For further information

    International Scientific Symposium on Angelman Syndrome 2014
    Date: 17-19 October, 2014
    Venue: Paris, France

    Organised by the French Angelman Syndrome Association (AFSA), the symposium will bring together international scientists studying the mechanisms associated with Angelman syndrome and promote exchanges between researchers to advance research in genetics and neuroscience on this rare disease. The meeting is open to official representatives of European and national Angelman syndrome organisations (up to 2 persons per organisation).
    For further information

    64th Annual Meeting of the American Society of Human Genetics: ASHG 2014
    Date: 18-22 October, 2014
    Venue: San Diego, US

    The ASHG Annual Meeting is the largest human genetics meeting and exposition in the world. This year’s meeting is expected to attract over 6,500 scientific attendees and over 200 exhibiting companies. ASHG members and leading scientists from around the world are selected to present their research findings at invited, platform, and poster sessions. Abstracts of work submitted for presentation at the Annual Meeting are published online and are citable. ASHG's Annual Meeting also features a trade show floor that offers attendees the opportunity to view state-of-the-art medical and laboratory equipment, products, services, and computer software designed to enhance human genetics research, teaching, and consultation.
    For further information

    NORD’s Rare Diseases and Orphan Products Breakthrough Summit
    Date: 22-23 October, 2014
    Venue: Alexandria, Virginia, US

    The 2014 Breakthrough Summit will concentrate on innovative content and will welcome the top leaders from the FDA, NIH, Industry, Patient Groups, Payers and Research Institutions to address the progress of rare disease diagnosis, genomics, drug development, patient engagement, product approvals, FDA oversight and market accessibility to orphan products.
    For further information

    14th International Congress on Neuronal Ceroid Lipofuscinoses (Batten Disease)
    Date: 22-25 October, 2014
    Venue: Córdoba, Argentina

    Batten disease is a common name for a group of rare, neurodegenerative genetic disorder affecting approximately 1 in 30,000 individuals. This conference will bring together experts on the latest research into Batten disease, experimental therapies, and clinical perspectives. Workshops will also be organised, covering topics such as patient registries and ethical issues.
    For further information

    International VHL Medical Symposium
    Date: 23-25 October, 2014
    Venue: Madrid, Spain

    Biennial International VHL Medical Symposia bring together the leaders in VHL basic, translational and clinical research, as well as the leading clinicians in clinical treatment for VHL. The gathering creates a stimulating environment while helping to make connections among these professionals that will spur the pace of progress in understanding and treating VHL. The content is aimed at medical researchers and healthcare professionals. Patients and caregivers are encouraged to attend. Their participation is highly valued as they are the true authorities of von Hippel-Lindau.
    For further information

    30th Annual Meeting of the Histiocyte Society
    Date: 28-30 October, 2014
    Venue: Toronto, Canada

    The Annual Meeting of the Histiocyte Society serves as the main forum for many of the world's most accomplished histiocytosis researchers and medical professionals to engage in vital collaboration and dialogue with one another. This year, the Society's 30th Annual Meeting will feature presentations on the study and treatment of the histiocytic disorders. Society members will present updates on ongoing Society-sponsored clinical trials on the histiocytic disorders.
    For further information

    ESID Meeting 2014
    Date: 29 October - 1 November, 2014
    Venue: Prague, Czech Republic

    The 16th Biennial Meeting of the European Society for Immunodeficiencies (ESID 2014), offers access to the latest research and analysis in the field. Meeting participants will gain insights into innovative perspectives in both basic and clinical research. The scientific programme will draw together experts from around the world to discuss breakthroughs in diagnostic immunology, genetics and immunobiology of human diseases, advances in clinical practice, novel therapeutic approaches to tolerance induction and new insights into stem-cell and cellular therapies.
    For further information

    Date: 30 October, 2014
    Venue: Rome, Italy

    As a part of its programme the E-Rare Consortium is organising the special Symposium dedicated to collaboration in rare diseases research. The event will gather rare diseases stakeholders: funders, researchers, patient organisations and regulatory bodies. Three symposium sessions will give an overview on how cooperation among funders, scientists and other relevant stakeholders helps advance rare diseases research with ultimate patient benefits. E-Rare will take this opportunity to present its future plans and activities in the context of the forthcoming "E-Rare-3" action.
    For further information

    New frontiers in Neuroacanthocytosis and Neurodegeneration with Brain Iron Accumulation: From Benchside to Bedside
    Date: 30 October - 1 November, 2014
    Venue: Stresa, Italy

    This third joint symposium on Neuroacanthocytosis addresses neurologists, interns, haematologists and biotechnologists working in the field of diagnostic, clinical and therapeutic management of patients affected by Neuroacanthocytosis and brain iron accumulation diseases. The scientific issues of this meeting will cover both the identification and characterisation of new aspects of this condition, as well as clinical developments.
    The international NBIA umbrella patient organisation NBIA Alliance offers travel grants for postdoctoral fellows and early career clinical doctors, involved in NBIA research and interested to attend the 3rd Joint NA & NBIA Symposium.
    For further information

    2nd International Rare Diseases Research Consortium (IRDiRC) Conference
    Date: 7-9 November, 2014
    Venue: Shenzhen, China

    The second conference is organised by the International Rare Diseases Research Consortium (IRDiRC), in collaboration with the BGI. The conference will gather top scientists from Europe, North America and Asia-Pacific for dynamic exchanges on knowledge and expertise. The event will also include an educational track. The ambition of this conference is to provide researchers with opportunities to establish new collaborations and confront different cultural approaches to the challenges posed by rare diseases.
    For further information

    4th Pan-European Conference on Haemoglobulinopathies and Rare Anaemias
    Date: 7-9 November, 2014
    Venue: Athens, Greece

    The 4th Pan-European Conference on Haemoglobinopathies and Rare Anaemias aims to educate and empower patients, develop European expert collaborative networks and improve multidisciplinary interaction concerning policy decision making.
    For further information

    Third International Symposium on Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS)
    Date: 12-13 November, 2014
    Venue: Montreal, Canada

    The Montreal Neurological Institute and Hospital will host the 3rd International Symposium focusing on advances in understanding ARSACS (Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay) in the larger context of mitochondrial dysfunction in neurodegeneration. This two day symposium will bring together clinical, ataxia, and mitochondrial experts, as well as drug developers, to discuss how to accelerate the discovery of treatments for ARSACS.
    For further information

    Ataxia Telangiectasia Clinical Research Conference 2014
    Date: 13-15 November, 2014
    Venue: Nijmegen, The Netherlands

    The bi-annual A-T Clinical Research Conference 2014 brings together leading figures from the fields of clinical science and translational research in Ataxia-Telangiectasia. The objective of the conference is to share knowledge and map progress in the fields of current research and help identify priorities for future research and opportunities for collaboration. The programme includes lectures, presentation of selected abstracts, a poster session, four workshops, a ‘best poster prize’ and a social programme.
    For further information

    Cilia 2014
    Date: 18-21 November, 2014
    Venue: Paris, France

    Cilia 2014 will focus on (but not be limited to) recent advances in cilia structure and function, including trafficking, cilia and development, cilia in human genetic disease and cilia in infectious microorganisms. The event is organised by four European cilia networks: GDR CIL (France), the Ciliopathy Alliance, the Nordic Cilia & Centrosome Network (Scandinavia) and the EU-FP7 SYSCILIA programme.
    For further information

    European Williams Syndrome Conference
    Date: 21-23 November, 2014
    Venue: Budapest, Hungary

    The European Federation of Williams Syndrome (FEWS) organises, with the Hungarian Williams Syndrome Association (HWSA), this conference to raise awareness, increase interaction between stakeholders and establish international cooperation.
    The focus is to share good practice and knowledge on the disease between European Countries with a good expertise and other European Countries with lesser experience on the syndrome. The ultimate goal is to improve patient care and contribute to EU policy on rare diseases.
    The conference targets healthcare professionals, caregivers, politicians, patient organisations, researchers and academics, national authorities, medical societies, health industry, media, etc., as well as professionals from countries with limited knowledge about the syndrome, in order to spread awareness.
    For further information

    22nd René Touraine Foundation for Dermatology Scientific Meeting
    Date: 5 December, 2014
    Venue: Paris, France

    Every year, the Scientific Meetings go over any acquired knowledge on one skin cell. Mornings are reserved for fundamental approaches, while afternoons are devoted to approaches applied to physiopathology, pharmacology and therapeutic. These are multi-subject meetings. Each presentation starts with a general overview of the terminology used, and continues with the speaker’s own research.
    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 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

    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

    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

    Orphan Drugs and Rare Diseases
    Date: 20-21 October, 2014
    Venue: London, UK

    SMi present the 3rd Annual Orphan Drugs and Rare Diseases Conference. The Orphan Drugs market is set to rise as a result of pharmaceutical companies now looking to orphan drugs as an essential revenue stream with 2014 set to be the year to see Orphan adoption.
    For further information

    3rd annual World Biosimilar Congress
    Date: 11-12 November, 2014
    Venue: Geneva, Switzerland

    The 3rd annual World Biosimilar Congress offers keynotes, case studies and roundtables covering topics relating to process, production, regulation and marketing strategies for biosimilars. Speakers and attendees include industry executives, middle managers, academics, key influencers and end-users.
    For further information

    The World Orphan Drug Congress Europe 2014
    Date: 12-14 November, 2014
    Venue: Brussels, Belgium

    The World Orphan Drug Congress Europe offers partnering opportunities in the orphan and rare disease field. Key networking platforms include: Dedicated networking functions; Privately hosted meeting areas; Online partnering portal and access to free smartphone app; Personal networking managers to assist in meeting scheduling.
    For further information


    Media, Press & Publications

    “Driving Blind”: a road trip documentary of two brothers suffering from degenerative eye disease Choroideremia

    Brothers Tod and Justin Purvis suffer from degenerative eye disease Choroideremia, an X-linked chorioretinal dystrophy causing progressive degeneration of the choroid, retinal pigment epithelium and retina. The brothers travelled across the United States, exploring urban and rural sights, camping on the way and discovering the beauty of their country before their vision becomes severely impaired. They have produced a documentary of their travels, Driving Blind, to illustrate their appreciation of what life has offered them until now.

    For further information and access to the film


    OrphaNews, The Newsletter of the Rare Diseases Community.
    OrphaNews 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: Antonia Mills
    Editors for Scientific Content: Catherine Pouzat, Sophie Höhn
    Contact Us
    Editorial Board: Ségolène Aymé, Paul Boom, Anna Bucsics, Kate Bushby, Barbara Cagniard, Lorenzo Dagna, Adam Heathfield, Lilian Lau, Yann Le Cam, Jordi Llinares-Garcia, Antoni Monserrat, Charlotte Rodwell, Gerhard Steffes, Till Voigtländer, Jaroslaw Waligora

    Orphanet Partner Country Representatives: Kristine Hovhannesyan (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), 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), Ugur Ozbek (Turkey), Dian Donnai (UK)
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