6 December 2014 print
Nat Pol News
ELS News
EU Project
New Syndromes
New Genes
Research in Action
Patient Man & Therapy
Orphan Drugs
Courses & Education
What's on?
Media, Press & Publications
Subscribe / Unsubscribe
Search the Orphanews archives :


Two significant steps towards improved codification for rare diseases

Currently, only a small fraction of rare diseases have codes in international nomenclatures, making it a challenge to trace patients with rare diseases in health information systems on a national and international level. Having codes for each rare disease would help European and national health authorities obtain a better knowledge of healthcare pathways and of their impact on specialised health care services (centres of expertise for instance) as well as on a country’s budget planning for health and social service.

Although much headway has been made to ensure that the rarest diseases will appear in the next version of the International Classification of Diseases (ICD11) currently available in a beta version, the release date of this classification is not scheduled until 2017, and implementation may be much later. In order to ensure that rare diseases can be traced in health information systems as soon as possible, Orpha codes, which are linked with ICD11, are proposed as a complementary coding system when a code does not exist for a rare disease. Two steps were recently made to improve the codification of rare diseases in the form of the adoption of the Commission Expert Group on Rare Diseases’ first recommendation on ways to improve codification for rare diseases (Read the coding recommendation), and an expert workshop aimed at sharing experiences and approaches to the use of Orpha codes as a complementary coding system.

A first recommendation for the Commission Expert Group on Rare Disease focuses on improving codification
The European Commission Expert Group on Rare Diseases adopted its first recommendation on codification for rare diseases at their third meeting last month. Addressed to the MS and the European Commission, it outlines the state of play in the field, and provides the rationale for the use of Orpha codes as a complementary coding system when no specific code exists for a rare disease.

Six recommendations are proposed to improve the codification of rare diseases in health information systems. These include the need to consider a complementary approach whilst rare diseases are incorporated into ICD and SNOMED-CT; the importance of exchanging experiences on the use of Orphacodes at national level through a working group to be established in a future EU Joint Action on rare diseases ; and the further promotion of Orphacodes within the ICD11 revision process taking place at the World Health Organization. Member States are encouraged to consider and explore the feasibility of the use of Orphacodes at national level and to include the codification of rare diseases as an area of their national plans/strategies for rare diseases. The recommendation concludes with a strong encouragement for EU Member States and the European Commission to seek possibilities to support the implementation of identified solutions.

Exchanging experiences and approaches to coding rare diseases
On 1-2 October 2014, the European Commission's Joint Research Centre (JRC) hosted a workshop to explore the best ways in which to improve the codification of rare diseases in health information systems through the complementary use of Orphacodes. Orphacodes are the codes attributed to all rare diseases within the Orphanet classification. Experts from the fields of coding and registries joined Member State representatives to discuss the possible models for implementation of the additional Orphacodes at national level alongside the terminologies currently in use, as well as the possible areas of European collaboration to facilitate the use of data for rare diseases research in the future.

Participants agreed that coding systems, tools and practices around Europe are highly heterogenous and that a sole solution adapted to all countries' needs is unrealistic. However, a majority of European countries are interested in making rare disease patients visible in their health information systems using an Orphacode as a complementary code when one does not exist in the terminology they currently use. It was decided to promote further exchange between the countries interested in using Orphacodes and those that do so already so as to help countries define the best strategy, notably through the development of an alignment of Orphacodes and the versions of the International Classification of Diseases (ICD) used in each country. Although all efforts to implement Orphacodes will be carried out at national level due to national specificities, a common approach for data exploitation will be needed at European level in the future.
Consult the report from the workshop on Orphacodes in Health Information Systems.

These two steps bring the rare disease community a little further forward towards the goal of making rare diseases visible in health information systems. Once an effective system is in place, a wealth of information will be made available to help improve our knowledge of healthcare pathways, which will hopefully lead to improved planning of health and social services.
Read the flash report on the proceedings of the meeting of Commission Expert Group on Rare Diseases held on 12-13 November 2014

National & International Policy Developments
Other European news
Abstracts from the 7th European Conference on Rare Diseases and Orphan Products -2014, now available
The 7th European Conference on Rare Diseases and Orphan Products was held in Berlin from 8-10 May. This conference, organised by EURORDIS, in collaboration with the DIA, was attended by more than 750 participants from over 40 countries, who contributed to the success of this informative conference. The conference activities centred around issues and topics that affect rare disease stakeholders and took stock of what has already been achieved and future endeavours that will aid in improving the quality of life of rare disease patients. The conference concentrated on six themes: Improving Healthcare Services; Knowledge Generation & Dissemination; Research from Discovery to Patients; State of the Art & Innovative Practices in Orphan Products; Emerging Concepts & Future Policies for Rare Disease Therapies; and Beyond Medical Care, which provided much needed information to rare disease patients. EURORDIS and DIA have provided access to information presented in this conference to those who were unable to attend the conference by providing links to the presentations.
The abstracts from this enlightening conference have been published and are freely available in the Orphanet Journal of Rare Diseases.
IQWiG recommends randomised control trials for orphan drugs
On behalf of the Federal Ministry of Health (BMG), the German Institute for Quality and Efficiency in Health Care (IQWiG) analysed the studies on which approval of orphan drugs are based in Europe. Based on their analyses, IQWiG concluded that randomised control trial (RCT) should be the norm and not the exception for studies on rare disease. The report states that clinical trials with low number of participants is not a preferable scenario as the effect on small populations can only be determined if they are studied in sufficiently large samples, and IQWiG believes that this should be possible using disease networks and registries of patients. According to the report, decreasing precision by increasing the significance level is preferred to decreasing sample size and therefore advocate raising the level of significance above 5-10%. IQWiG believes that raising the significance level will allow the estimation of the level of uncertainty. IQWiG also observed that 82 out of the 125 studies for rare disease approvals, submitted to EMA between 2001 and 2013, were RCTs and therefore conclude that it is not necessary to change course and accept drug approvals based on small sample sizes. Although IQWiG qualifies their analysis with the statement “all patients have a right to quality”, it must be noted that demanding RCTs for all orphan drugs may limit access to drugs for rare disease patients, which can be inequitable as well.
Read the IQWiG Report

Conditional reimbursement practices in the Netherland analysed
With the advent of prohibitively expensive orphan drugs, the Dutch government introduced a policy whereby they could be financed, with the criteria that the expected cost-effectiveness be incorporated in its reimbursement application. Reimbursement based on expected cost-effectiveness was considered temporary and the drug would be re-evaluated based on data collected for the drug, over a period of four years. Whether this re-evaluation was optimal is analysed in an article published in Health Policy.

The analysis performed by the authors revealed that collaborations between institutional structures, such as those supporting medical specialists and patient organisations, led to faster production of the required data on cost-effectiveness. According to the authors, "this mode of governance can overcome difficulties in transparency, legitimacy and feasibility of additional studies".

Evaluation of the outcomes showed that the relevance of cost-effectiveness findings is unclear and seems to be outweighed by political and ethical considerations that enter the debate after publication of the advice. Additionally, the quality of the cost-effectiveness findings were widely questioned by stakeholders, including the researchers.
Consult the abstract

The National Strategy of Denmark makes recommendations for the rare disease management in Denmark
In Denmark, many actions concerning the provision of healthcare for rare diseases were carried out following the recommendations of a report concerning rare diseases issued in 2001. A working group of stakeholders was established in 2012 with the task to elaborate a comprehensive national strategy for rare diseases in Denmark based on the experiences of the implementation of the recommendations the 2001 report and the national designations of centres of expertise in 2010. A Danish Strategy for Rare Diseases was submitted in 2014.The National Strategy of Rare Diseases in Denmark-2014 has made several recommendations aimed towards better care and increased research and development in the area of rare diseases.

The strategy recognises that severe, genetic or congenital disorders are often complex as well as the need to enhance the knowledge of incidence and prevalence of rare diseases from the data in clinical registries and databases in Denmark. The requirement for expert centres for rare diseases is also underscored. Increased focus on early and timely diagnosis as well as helping patients gain direct referral to centres of expertise for treatment and follow-up are emphasised. Building special awareness for "real orphans", and a special attention on facilitating a smooth transition to adulthood for rare disease patients who are diagnosed early is recommended. General guidelines for the usage of new technologies include the need for appropriate genetic testing, preferring clinical examinations to precede advanced genetic testing.

Recommendations for learned medical societies, which constitutes a working group centered around a specific rare disease, as well as greater awareness for rare diseases and related activities are outlined. The continuation and expansion of the Raredis database through permanent financing is strongly advocated.

According to the Strategy, activities in national coordination should encompass rebuilding specialised social services, as well as constructing a pathway for easy access of up-to-date information on rare diseases in Danish for professionals and patients. The reorganisation of the diagnosis descriptions as well as securing regular updates for a strong robust health setting is suggested. Denmark is currently working in collaboration with Orphanet to establish an overview of Danish sources of information registries for rare disease patients. The strategy recommends that an agreement on systematic and precise classification is reached with the help of OMIM codes.

The strategy recommends empowering patients and patient organisations. They recommend creating and fostering avenues where rare disease patients can join networks and participate in social activities. A larger voice for patient organisations in the public sphere, especially in legislative matters, is highly recommended, as is the continuation and additional funding of “Sjældne netværk”.

Finally, the importance of Denmark in the continual participation in EU activities regarding rare diseases such as participation in the Commissions Expert Group, as well as EUnetHTA is emphasised.

According to the strategy, this rare disease plan should be implemented before 2018, with an evaluation over 3-5 years from 2014. The recommendations are geared towards health authorities regions, Danish Health and Medicines Authority (DHMA), research funds, GPs, hospitals municipalities, social and educational authorities, medical societies and patient organisations.
Please note that the document on the National Strategy of Rare Diseases in Denmark-2014 is currently not available online

Other International News
Surrogate endpoints for clinical trials an urgent requirement for drug approvals by Japanese regulatory agency
An article published in the Annals of Oncology discusses the endpoints for clinical trials that need to be accepted by the Pharmaceuticals and Medical Devices Agency (PMDA) of Japan to approve oncology drugs. The authors inform that even though acceptance of surrogate endpoints is crucial for accelerated approval of drugs, the number of surrogate endpoints has decreased after the revision of guidelines in Japan. Although Japan has many expedited programs in regulatory systems including orphan drug designation, priority review, public knowledge-based application, and a special committee on unapproved drugs, they are lagging behind the US and EU in drug approvals. The authors believe that an accelerated approval program, and a system for discussing surrogate endpoints so far, is called for in order to bring oncology drugs to the needy patients faster.
Consult the Pubmed abstract

The second Ibero-American Rare Diseases Meeting: ALIBER discusses the trajectory for rare disease stakeholders in Latin America
The second Ibero-American Rare Diseases Meeting held in early November this year in Moita, Portugal gathered stakeholders interested in improving the situation for rare disease patients in Latin America. The event provided the opportunity to discuss and bring forth issues relating to rare disease patients and the initiatives taken to address the concerns of these patients. Ibero-American Rare Diseases Alliance (ALIBER) took this opportunity to discuss specific issues relating to the rare disease patient experience in Latin America and aim to create rare disease state-of-the-art reports for each member country. The conference discussed progress being made in health policy for rare disease patients in Argentina, Brazil, Mexico, Uruguay and other Latin American countries as well as the strategies for the future. Apart from rare disease stakeholders, the conference was also graced with the presence of eminent personalities like Her Majesty the Queen Letizia of Spain and First Lady of Portugal, Maria Cavaco Silva. Due to the grand success of this meeting, the third Ibero-American rare disease stakeholders is planned and scheduled to take place in Guadalajara, Mexico, in 2015.
Read the article published on the Eurordis website
Visit the Fedra website
Visit the Aliber website

Challenging gene patents for diagnosing Long Q-T syndrome in Canada
In Canada, the Children’s Hospital of Eastern Ontario are challenging patents held by companies on genes in the Federal Court of Canada. The hospital is specifically challenging the patent held on a genetic test for long QT syndrome – a rare inherited genetic disorder, which has fatal consequences. Testing for the gene in people with a family history of the disorder can help doctors prevent incidents in high-risk patients before they happen. Test for long QT syndrome costs CAD 4500 and, when incidentally discovered in a patient, cannot be revealed to that patient and the doctors can be prevented from learning anything further, due to the patents held by a US company –Transgenomic North America. This violation of patient rights and incorrect usage of patenting has been taken to the Federal Court on medical and ethical grounds, citing barriers that gene patents present in providing tests for genetic diseases.
Read more on this topic
Read the article in CHEO
Read the article in GenomeWeb
Read the article in Radio Canada International
Read the article in The Canadian Press
Read the article in Huffington Post
Read the article in Toronto Star

Taiwanese system of providing care for children with a development delay
A review published in Pediatrics and Neonatology introduces the screening and referral network of genetic evaluation for children with developmental delay in Taiwan. According to the article, all cities and counties in Taiwan have an established network for screening, detection, referral, evaluation, and intervention services. The authors believe that Taiwan provides children with developmental delay services from the medical, educational, and social welfare sectors and has an opportunity for increased awareness to improve early detection and intervention. However, they also allude to the lack of resources, due to which there is limited access to advanced genetic testing such as microarray or whole exome testing for these conditions. Despite this, the authors believe that Taiwan works in a gainful manner, which may be an example for countries with limited resources.
Consult the abstract

Inauguration of a dental center for children with special needs in Lebanon
Lebanese children with special needs are usually supported by non-governmental organisations (NGOs) for their education and health. Children with psychomotor or mental impairment, as well as children with rare diseases usually come from a low socio-economic background and hence have difficulty finding qualified professionals to support their oral health.

For the past thirty years, the Department of Paediatric Dentistry at the Lebanese University has welcomed children with crippling disorders for dental care. However, the number of children needing this care has been increasing, and to meet their needs, a dental centre designed to house and care for children with disabilities, promote research and foster communication with parents, was inaugurated in June 2014. The inauguration was attended by the Rector of the University, the Minister of Social Affairs and the donor that financed infrastructure for this center - Al Waleed Bin Talal foundation. This centre provides care that is equivalent to that offered by other international reference centres for oral manifestations of rare diseases. The centre is coordinated by Prof. Elia Sfeir and Balsam Soubra and the team responsible for overseeing the management of patients consists of dentists from the department. The collaborative team consists of a physician anaesthesiologist, an autism specialist, a paediatrician, a nutritionist, a specialist in biomolecular research, a multidisciplinary dental team and search platform in molecular biology from the Faculty of Science at the Lebanese University. A partnership has also been established with the National Reference Centre for Dental Manifestations of Rare Diseases, University Hospital of Strasbourg, coordinated by Prof. Manière.
For further information contact Prof. Elia Sfeir

Guidance Documents and Recommendations
Clinical Guidelines for Ataxia-telangiectasia
The publication of the first ever clinical guidance on the treatment of ataxia-telangiectasia (A-T) was enthusiastically welcomed by clinicians, therapists and families living with the condition. (A-T) is a rare genetic multi-system neuro-degenerative disorder, which from early childhood leads to increasing physical disability and significantly shortens lives. Ataxia-telangiectasia in children: Guidance on diagnosis and clinical care was produced by members of the multidisciplinary team from the A-T Specialist Centre at Nottingham City Hospital, the University of Birmingham and the A-T Society. This guidance document will ensure that, for the first time, there is a shared understanding of the symptoms and progress of the condition and a consistent approach to treating it, based on the experience of the world’s longest-established multi-disciplinary A-T clinic. The document is primarily aimed at clinicians and other health professionals that have little first-hand experience of treating A-T. However, it will also to be used by those caring for children with A-T to ensure that they are receiving the best possible care. The document can be downloaded from the A-T Society’s website www.atsociety.org.uk/clinical-guidance or a printed copy can be requested from info@atsociety.org.uk
Screening and Testing
Article recommends refining clinical genomic reports to improve clarity and efficiency
In order to effectively articulate the results of exome and genome sequencing, the authors of an article published in the American Journal of Medical Genetics Part C: Seminars in Medical Genetics have refined the structure and content of molecular test reports. They developed this revised report in order to communicate results of a randomised control trial, which was aimed at the evaluation of exome sequencing for clinical medicine. However, the authors believe that the report format that they have developed to communicate research results can easily be transformed for clinical use. In order to effectively commnunicate the test results the authors prepared a structured narrative report as well as a separate indication‐specific and incidental findings reports, after detailed consultations with genetics and non-genetics professionals. The authors believe that increasingly complex nature of testing warrants an open interaction between the clinician and the laboratory, which in turn will help them deliver accurate and efficient results of exome sequencing.
Consult the Pubmed abstract


Ethical, Legal & Social Issues
To give or not to give: the question of returning incidental finding to children
An article published in Current Genetic Medicine Reports, discusses the aspects of genomic information dissemination in the context of children. There are several biological and ethical aspects that are necessary to comprehend before making recommendations and guidelines for the return of genetic diagnosis to children, which may make or break their future. The article examines American College of Medical Genetics (ACMG) recommendations on the return of incidental findings in the context of genetic testing for children some of which, according to the authors, is contentious.

The authors believe that if there was an unexpected ‘‘incidental’’ genetic finding associated with a serious childhood-onset condition that is clinically actionable, parents should not have the option of opting out of receiving such a result, however, parents should have the option of opting out of the deliberate search for secondary findings as this falls under the rubric of screening. Further the authors believe that while disclosing results for conditions that are of adult onset but not treatable or preventable, it is in the best interest of the child to protect the child’s future autonomy, and this interest overrides the parents’ right to know this information. However, the author also maintain that when the discovery of gene variant in child makes it likely that the child has inherited it from the parent and telling the parent would improve the quality of life of the parent and believe that a parent who receives such a sequencing result regarding his/her child is afforded the opportunity to find information important to his/her own health. In this case, negating the child’s future right not-to-know or to decide whether to be tested—i.e., violating the child’s future autonomy may be in the best interests of the child, as it may enable the child to have parents who are alive and healthy.
Consult the Pubmed abstract

Another study published in European Journal of Human Genetics, also addressed the ethical question raised in the above review. However, in this study the general population was asked what they felt about genetic testing in children for conditions that will manifest in adulthood, which may not have an adequate intervention. The authors found that the general population viewed testing in a manner that is contrary to the attitudes of healthcare professionals and current guidelines and recommendations.

Nearly half of the population that the authors questioned were in favour of parents being able to test for adult-onset conditions. More than half the participants supported testing for carrier status, while a child’s right to decide was supported the least, even when there was no known intervention for the condition. From these results, the authors deduce that the participants feel the right to information and the right to decide of the parents was paramount because they believed that even when there are no known interventions, parents may benefit from the information in some way. The authors believe that their findings suggest that the healthcare professionals may have to propose deferring the test by providing the parents reasons that are easily relatable “(such as) the fear of discrimination and stigmatisation, the lack of medical utility and the possibility of misinforming the child in the future about their test results”.
Consult the abstract


EU Project Follow-up
Linked2Safety project: secure medical information space for analysing clinical data
The Linked2Safety project, funded under the FP7 scheme of the European Commission, is built to advance clinical practice and accelerate medical research, by providing pharmaceutical companies, healthcare professionals and patients with an “innovative semantic interoperability framework facilitating efficient and homogenised access to distributed Electronic Health Records (EHRs)”.

Electronic Health Records (EHRs) contain an increasing wealth of medical information and have the potential to significantly advance medical research, as well as improve health policies. However, the European healthcare information space is fragmented due to the lack of legal and technical standards, cost effective platforms, and sustainable business models. Linked2Safety is a platform for analysing EHRs from multiple institutions, while strictly adhering to the legal and ethical requirements as defined by each data provider at EU level.

Benefits for this 36-month Linked2Safety project include facilitating the analyses all available data in the EHRs, which include the genetic, environmental and medical history of subjects exhibiting adverse events during clinical trial, which in turn will help in providing genotype-phenotype associations. It will also provide a platform for identification and selection of patients for clinical trials by linking EHR repositories.
Go to the Linked2safety website


New Syndromes

Novel predominant ocular phenotype with high myopia, esotropia, vitreous changes and cataract linked to a new mutation in LRP2 in two siblings from a consanguineous Iraqi family
Two siblings, from a consanguineous Iraqi family, were investigated to identify the underlying genetic cause of their high myopia, esotropia, vitreous changes and cataract. Subsequent investigation identified low molecular weight proteinuria as part of their syndrome. Exome sequencing of one of the probands revealed a new non-synonymous variant in the LRP2 gene.
Consult the Pubmed abstract

Clin Genet. ; 86(3):282-6 ; September 2014
Autosomal recessive intellectual disability with muscular hypotonia, epilepsy and postnatal growth deficiency caused by NDST1 missense mutations in four families
NDST1 was recently proposed as a candidate gene for autosomal recessive intellectual disability in two families in another article. The authors of this article reported on two additional unrelated families with homozygous missense NDST1 mutations. Comparing the four families, they noticed significant overlap in the clinical features, including both demonstrated and apparent intellectual disability, muscular hypotonia, epilepsy, and postnatal growth deficiency.
Consult the Pubmed abstract

Am J Med Genet A. ; 164(11):2753-63 ; November 2014
A peroxisomal disorder of severe intellectual disability, epilepsy, and cataracts due to FAR1 deficiency in two families
The authors reported the identification of mutations in FAR1, in two families affected by severe intellectual disability, early-onset epilepsy, microcephaly, congenital cataracts, growth retardation, and spasticity.
Consult the abstract

American Journal of Human Genetics ; 95(5):602-610 ; November 2014
Novel syndrome of primordial dwarfism with microphthalmia and retinopathy
Two articles described a novel syndrome of primordial dwarfism with microphthalmia and retinopathy caused by mutations in PLK4.
Consult the Pubmed abstracts

J Med Genet. ; 51(12):814-6 ; December 2014
Nat Genet. ; 46(12):1283-92 ; December 2014
Seizures and intellectual, attention, and language deficits due to absent CNKSR2 in 8 patients
The authors described a disease caused by absence of the synaptic protein CNKSR2 in 8 patients ranging from 6 to 62 years old. The disease is characterized by intellectual disability, attention problems, and abrupt lifelong language loss following brief early childhood epilepsy with continuous spike-waves in sleep.
Consult the Pubmed abstract

Ann Neurol. ; 76(5):758-64 ; November 2014

New Genes

Intellectual disability and/or central obesity due to MYT1L mutations
Consult the Pubmed abstract
Genet Med. ; [Epub ahead of print] ; September 2014
Progressive non-syndromic genetic deafness: OSBPL2 as a novel candidate gene
Consult the Pubmed abstract
To read more about "Non-syndromic genetic deafness"

Genet Med. ; [Epub ahead of print] ; July 2014
MELAS associated with a novel MTCYB mutation in a young patient with recurrent stroke-like episodes and status epilepticus
Consult the Pubmed abstract
To read more about "MELAS"

Am J Med Genet A. ; 164(11):2922-5 ; November 2014
Inherited giant platelet disorder induced by a germ-line mutation in the PRKACG gene
Consult the Pubmed abstract
To read more about "Inherited giant platelet disorder"

Blood ; 124(16):2554-63 ; October 2014
Malignant epithelial tumor of the salivary glands caused by hotspot activating PRKD1 somatic mutations
Consult the Pubmed abstract
To read more about "Malignant epithelial tumor of the salivary glands"

Nat Genet. ; 46(11):1166-9 ; November 2014
5q31.3 microdeletion syndrome: mutations in PURA cause profound neonatal hypotonia, seizures, encephalopathy, severe neurodevelopmental delay and learning disability
Consult the abstract
Consult the Pubmed abstract

To read more about "5q31.3 microdeletion syndrome"

J Med Genet. ; 51(12):806-13 ; December 2014
Autosomal recessive axonal Charcot-Marie-Tooth disease type 2 caused by missense mutations in IGHMBP2 and HSJ1
Consult the abstract
Consult the Pubmed abstract

To read more about "Autosomal recessive axonal Charcot-Marie-Tooth disease type 2"

American Journal of Human Genetics ; 95(5):590-601 ; November 2014
Neurology ; 83(19):1726-32. ; November 2014
Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome due to causal mutations in SNX14 in seven individuals from three unrelated consanguineous families
Consult the abstract
To read more about "Intellectual disability-coarse face-macrocephaly-cerebellar hypotrophy syndrome"

American Journal of Human Genetics ; 95(5):611-621 ; November 2014
Filippi syndrome caused by loss-of-function mutations in CKAP2L
Consult the abstract
To read more about "Filippi syndrome"

American Journal of Human Genetics ; 95(5):622-632 ; November 2014
Amyotrophic lateral sclerosis: excess of rare damaging TUBA4A variants suggests cytoskeletal defects
Consult the Pubmed abstract
To read more about "Amyotrophic lateral sclerosis"

Neuron ; 84(2):324-31 ; October 2014

Research in Action

Clinical Research
Phenylketonuria: long-term developmental progression in infants and young children taking sapropterin
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Phenylketonuria"
To read more about "Tetrahydrobiopterin-responsive hyperphenylalaninemia/phenylketonuria"

Genet Med. ; [Epub ahead of print] ; September 2014
Fabry disease: safety of switching from agalsidase-β to agalsidase-α at the approved doses, with no loss of efficacy
Consult the Pubmed abstract
To read more about "Fabry disease"

Genet Med. ; 16(10):766-72 ; October 2014
Diffuse large B-cell lymphoma: intensive induction may cure a subset of patients and benefit some of them
Consult the Pubmed abstract
To read more about "Diffuse large B-cell lymphoma"

Blood ; 124(15):2354-61 ; October 2014
Inherited retinopathies: review on available platforms for gene therapy
Consult the Pubmed abstract
Prog Retin Eye Res. ; 43C:108-128 ; November 2014
Duchenne or Becker muscular dystrophy: higher frequency of intellectual and mental health problems for early-manifesting females than for affected males and symptomatic females
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"
To read more about "Becker muscular dystrophy"

Am J Med Genet A. ; 164(11):2769-74 ; November 2014
Leber congenital amaurosis: promising results of a non-invasive oral QLT091001 therapy in a phase 1b trial
Consult the Pubmed abstract
To read more about "Leber congenital amaurosis"

Lancet ; 384(9953):1513-20 ; October 2014
ANCA-associated vasculitis: more patients had sustained remission with rituximab than with azathioprine
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Granulomatosis with polyangiitis"
To read more about "Microscopic polyangiitis"
To read more about "Anti-neutrophil cytoplasmic antibody-associated vasculitis"

N Engl J Med. ; 371(19):1771-80 ; November 2014
Indolent lymphoma: lenalidomide plus rituximab is well tolerated and highly active as initial treatment
Consult the abstract
To read more about "Indolent B-cell non-Hodgkin lymphoma"
To read more about "Marginal zone lymphoma"
To read more about "Follicular lymphoma"
To read more about "CEDNIK syndrome"

Lancet Oncol. ; 15:1311-1318 ; November 2014
Vulvar intraepithelial neoplasia: cidofovir and imiquimod as effective alternatives to surgery for female patients
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Vulvar intraepithelial neoplasia"

Lancet Oncol. ; 15:1361-68 ; November 2014
Hepatocellular carcinoma: brivanib as adjuvant therapy to transarterial chemoembolization did not improve overall survival
Consult the Pubmed abstract
Consult this study on Orphanet

To read more about "Hepatocellular carcinoma"

Hepatology ; 60(5):1697-707 ; November 2014
Glycogen storage disease due to acid maltase deficiency: combination of enzyme therapy and a chaperone enhances α-glucosidase activity
Consult the Pubmed abstract
To read more about "Glycogen storage disease due to acid maltase deficiency"

Mol Ther. ; 22(11):2004-12 ; November 2014
Facioscapulohumeral dystrophy: both aerobic exercise and cognitive-behavioral therapy reduce chronic fatigue
Consult the Pubmed abstract
To read more about "Facioscapulohumeral dystrophy"

Neurology ; 83(21):1914-22 ; November 2014
Therapeutic Approaches

Adult neuronal ceroid lipofuscinosis: Caenorhabditis elegans orthologue of DNAJC5 provides a new platform for neuroprotective drug screening and revealed resveratrol action
Consult the Pubmed abstract
To read more about "Adult neuronal ceroid lipofuscinosis"

Hum Mol Genet. ; 23(22):5916-27 ; November 2014
Huntington disease: phosphorodiamidate morpholino oligomers suppress mutant huntingtin expression and attenuate neurotoxicity
Consult the Pubmed abstract
To read more about "Huntington disease"

Hum Mol Genet. ; 23(23):6302-17 ; December 2014
Duchenne muscular dystrophy: forelimb treatment in a large cohort of dystrophic dogs supports delivery of a recombinant adeno-associated virus for exon skipping in patients
Consult the Pubmed abstract
To read more about "Duchenne muscular dystrophy"

Mol Ther. ; 22(11):1923-35 ; November 2014
Autosomal recessive limb-girdle muscular dystrophy type 2I: muscle and heart function restoration in a mouse model by systemic FKRP gene delivery
Consult the Pubmed abstract
To read more about "Autosomal recessive limb-girdle muscular dystrophy type 2I"

Mol Ther. ; 22(11):1890-9 ; November 2014
Mesothelioma: regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity
Consult the Pubmed abstract
To read more about "Mesothelioma"

Sci Transl Med. ; 6(261):261ra151 ; November 2014
Glioblastoma: integration of stem cell‐based engineering, multimodal imaging and delivery of PE‐cytotoxins in a cell model as a novel strategy and potential advancement
Consult the Pubmed abstract
To read more about "Glioblastoma"

Stem Cells ; [Epub ahead of print] ; October 2014
Pulmonary arterial hypertension: plasmid-based shRNA against connective tissue growth factor attenuated pulmonary vascular remodeling in monocrotaline-treated rats
Consult the Pubmed abstract
To read more about "Pulmonary arterial hypertension"

Gene Ther. ; 21(11):931-7 ; November 2014
Congenital pulmonary alveolar proteinosis: pulmonary macrophage transplantation was safe and corrected the lung disease in a mouse model
Consult the Pubmed abstract
To read more about "Congenital pulmonary alveolar proteinosis"

Nature ; 514(7523):450-4 ; October 2014
Diagnostic Approaches

Sézary syndrome: CD158k is a reliable marker for diagnosis and reveals unprecedented heterogeneity of circulating malignant cells
Consult the Pubmed abstract
To read more about "Sézary syndrome"

J Invest Dermatol. ; [Epub ahead of print] ; August 2014
Mucopolysaccharidosis type III: review of current practices in the laboratory diagnosis of mucopolysaccharidosis type III
Consult the Pubmed abstract
To read more about "Mucopolysaccharidosis type 3"

Mol Genet Metab. ; 113(1-2):34-41 ; October 2014
Very early onset inflammatory bowel disease: targeted gene panel sequencing in children and diagnostic approach
Consult the Pubmed abstracts
J Med Genet. ; 51(11):748-55 ; November 2014
Gastroenterology ; 147(5):990-1007 ; November 2014
Christianson syndrome: proposition of a core set of diagnostic criteria
Consult the Pubmed abstract
To read more about "Christianson syndrome"

Ann Neurol. ; 76(4):581-93 ; October 2014
Multiple myeloma: International Myeloma Working Group updated criteria for the diagnosis
Consult the abstract
To read more about "Multiple myeloma"

Lancet Oncology ; 15(12):e538-e548 ; November 2014
Genetic testing for spinocerebellar ataxia should be included for patients with multiple system atrophy, especially for patients with cerebellar dysfunctions
Consult the Pubmed abstract
To read more about "Multiple system atrophy"
To read more about "Autosomal dominant cerebellar ataxia"

Neurology ; 83(19):1733-8 ; November 2014
Systemic sclerosis: evidence for puffy fingers as a pivotal sign for suspicion of the disease
Consult the Pubmed abstract
To read more about "Systemic sclerosis"

Ann Rheum Dis. ; 73(12):2087-93 ; December 2014

Patient Management and Therapy
Giant cell arteritis: review on aspirin as adjunctive treatment
Consult the Pubmed abstract
To read more about "Giant cell arteritis"

Cochrane Database Syst Rev. ; 8:CD010453 ; August 2014
Acquired hemophilia: review on interventions for treating acute bleeding episodes
Consult the Pubmed abstract
To read more about "Acquired hemophilia"

Cochrane Database Syst Rev. ; 8:CD010761 ; August 2014
Mild hemophilia A: a review
Consult the Pubmed abstract
To read more about "Mild hemophilia A"

Blood ; 124(15):2333-2336 ; October 2014
X-linked creatine transporter deficiency: review on the treatment
Consult the Pubmed abstract
To read more about "X-linked creatine transporter deficiency"

Mol Genet Metab. ; 112(4):259-74 ; August 2014
Disorder of urea cycle metabolism and ammonia detoxification: sodium phenylbutyrate decreases plasma branched-chain amino acids
Consult the Pubmed abstract
To read more about "Disorder of urea cycle metabolism and ammonia detoxification"

Mol Genet Metab. ; 112(4):259-74 ; August 2014
Deferasirox nephrotocixity: a review
Consult the Pubmed abstract
Nat Rev Nephrol. ; 10(10):574-86 ; October 2014
Four new and twelve 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. Two new GeneReviews have been published for:
Barth syndrome
PNPLA6-related disorders
Arterial tortuosity syndrome
Generalized arterial calcification of infancy

Three updated GeneReviews have been published for:
Craniofacial microsomia
Giant axonal neuropathy
MECP2 duplication syndrome
Homocystinuria caused by cystathionine beta-synthase deficiency
Nail-patella syndrome
ATP1A3-related neurologic disorders
Aicardi syndrome
Alpha-thalassemia X-linked intellectual disability syndrome
Hereditary paraganglioma-pheochromocytoma syndromes
Sickle cell disease
Erythropoietic protoporphyria, autosomal recessive
X-linked hypophosphatemia

Four updated Clinical Utility Gene Cards 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 four updated Clinical Utility Gene Cards for:
Alport syndrome
Familial hypobetalipoproteinaemia


Orphan Drugs
Institute of Medicine’s Forum on Neuroscience and Nervous System Disorder identifies challenges and opportunities for drug development
A review published in Neuron expresses the difficulty of bringing drugs into the market that will benefit patients suffering from nervous system disorders. The authors have highlighted the outcome of a series of workshops conducted by the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorder, which includes the views of representatives of industry, regulatory agencies, academic and patient groups, in order to address the challenges associated with accelerating nervous system drug development. The workshop has identified several challenges that are hinder bringing innovative drugs targeting disorders of the brain, which includes dearth of information in several areas, such as “mechanisms of disease, target identification and validation, predictive models, biomarkers for patient stratification and as endpoints for clinical trials, clear regulatory pathways, reliability and reproducibility of published data, and data sharing and collaboration”. Keeping these challenges in mind, the authors have provided information on the opportunities that are currently available as well. Overall, the authors believe that the central approach to enhance and accelerate drug development in this area is to augment collaboration and data sharing.
Consult the Pubmed abstract

Regulatory News
State of the Art review of regulatory access and reimbursement options for innovative medicines in the US, the EU, Canada and Singapore
An informative review published in Clinical Pharmacology & Therapeutics outlines the regulatory activities geared towards accelerated access, as well the reimbursement benefits for patients in need, across four regulatory agencies. The authors have furnished two tables which provide comprehensive information on the existing, emerging and new regulatory access and reimbursement policies that have been put in place by the United States, Europe, Singapore and Canada to help pharmaceutical companies to bring innovative medicines to the market.

The paper describes in detail how sponsors can obtain accelerated access, the conditions under which it is provided, and how the assessment takes place. Even though orphan drug and paediatric drug initiatives were not designed to accelerate access of drugs to patients, these initiatives are frequently used to bring innovative drugs into the market. In the United States, programs such as Accelerated Access and Priority Review can help sponsors benefit from shortened clinical development and shortened review, respectively. The possible expedited clinical development time due to more intense FDA engagement, in Fast track, Breakthrough therapy regulatory programs are also focused on bringing innovative medicines for patients in need. The EU provides programs such as Conditional Marketing Authorisation and Approval Under Exceptional Circumstances, both of which allow sponsors to benefit from shortened development time, while Accelerated Assessment has reduced review time. The EU and the US also offer Parallel scientific advice between the EMA and the FDA where they align advice, hence reducing developmental complexity. In Canada, the orphan drug framework is an emerging regulatory process that is being developed for the regulation of orphan drugs. In Singapore, the process of abridged evaluation and verification has shortened processing time.

More diversity is observed reimbursement approaches for medicines than for regulatory approaches across the four jurisdictions. In the US, Coverage with Evidence Development, which is used by the Center for Medicare and Medicaid Services (CMS), provides early reimbursement of emerging technology. A new program in the US by the Center for Devices and Radiological Health where they work in coordination with CMS by shortening overall development time by collecting data needed by CMS earlier in development. The Managed-Access program in the US is an emerging policy which can be used by private payers to control post-market access to new medicines, but may require evidence of genetic mutation or other control mechanism. The EU has recently developed a similar managed entry program. However, in the EU, increasingly, “payers rely on Health Technology Assessment (HTA) bodies to provide information and analysis of the clinical, patient, organisational, and economic implications of new medicines, recognising that regulators are generally prohibited by law from taking economic considerations into their decision making”. The article details all the programs through HTA which helps in gaining data that informs reimbursement decisions. Canada has priority access by HTA and is working on programs along with the Institute national d’excellence en santé et en services sociaux to shorten reimbursement time. In Singapore, apart from the Standard Drug List that identifies the drugs to be subsidised at public health-care institutions and a group purchasing office that procures health products in bulk, the pricing of medicines is largely left to open market forces.

Consult the abstract

Positive opinions recommending orphan designation at the October and November 2014 COMP meeting
The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 29 positive opinions recommending the following medicines for designation as orphan medicinal products to the European Commission, issued at the October 2014 meeting for the:

- treatment of systemic sclerosis
- treatment of idiopathic pulmonary fibrosis
- treatment of cystic fibrosis
- treatment of limbal stem cell deficiency
- treatment of haemophilia A
- treatment of acute myeloid leukaemia
- treatment of acute respiratory distress syndrome
- treatment of myotonic disorders
- treatment of post-essential thrombocythaemia myelofibrosis
- treatment of post-polycythaemia vera myelofibrosis
- treatment of primary myelofibrosis
- treatment of plasma cell myeloma
- treatment of chronic lymphocytic leukaemia / small lymphocytic lymphoma
- treatment of microscopic polyangiitis
- treatment of granulomatosis with polyangiitis
- treatment of Gaucher disease
- treatment of Duchenne muscular dystrophy
- treatment of Niemann-Pick disease
- 2 treatments for mucopolysaccharidosis type I
- treatment of idiopathic pulmonary fibrosis
- treatment of hereditary haemorrhagic telangiectasia
- 2 treatments for glioma
- treatment of malignant hyperthermia
- treatment of hepatocellular carcinoma
- treatment of systemic sclerosis
- treatment of fibrodysplasia ossificans progressiva
- treatment of xeroderma pigmentosum
- treatment of dermatomyositis
- treatment of polymyositis

The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 27 positive opinions recommending the following medicines for designation as orphan medicinal products to the European Commission, issued at the November 2014 meeting for the:

- prevention of graft-versus-host disease
- treatment of familial cerebral cavernous malformations
- treatment of pancreatic cancer
- treatment of pleural empyema
- 2 treatments for WHIM syndrome
- treatment of neurotrophic keratitis
- treatment of multiple system atrophy
- treatment of ovarian cancer
- 2 treatments for glioma
- treatment of malignant mesothelioma
- treatment of Huntington’s disease
- treatment of acute lymphoblastic leukaemia
- treatment of acute myeloid leukaemia
- treatment of epidermolysis bullosa
- treatment of Pseudomonas aeuriginosa lung infections in cystic fibrosis
- treatment of non-infectious uveitis
- treatment of diffuse large B cell lymphoma
- treatment of beta-thalassaemia intermedia and major
- treatment of hereditary haemorrhagic telangiectasia
- treatment of inborn errors in primary bile acid synthesis
- treatment of amyotrophic lateral sclerosis
- treatment of malignant mesothelioma
- treatment of pancreatic cancer
- treatment of traumatic spinal cord injury

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
Should the definition of rare disease be changed based on the feasibility of randomised controlled trials?
An article published in Value in Health analyses whether the current method of designating a disease as rare is valid. Since pharmaceutical companies receive substantial benefits from regulatory agencies when they bring orphan drugs into the market, the authors believe that the designation of “rare disease” has major financial consequences. They believe that existing definitions, which are based on disease incidence or prevalence, is arbitraty and therefore have proposed a definition based “the feasibility of measuring the efficacy of a new treatment in conventional randomized controlled trials (RCT)”. The authors have suggested a five-step process, involving intense negotiations with rare disease stakeholders, to establish the feasibility of carrying out an RCT for a specific disease with a genetic diagnosis. The authors believe that following this process would provide an improved system of designating a disease as rare.
Consult the abstract



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

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

ERare : Joint Transnational Call 2015 Preannouncement
On the 15th of December 2014 ERare intend to open the seventh ERare joint call for funding multilateral research projects on rare diseases (JTC 2015) together with the European Commission (EC) under the ERANet cofund mechanism. The call is expected to be opened simultaneously by the parties in their respective countries. The following 17 countries (23 funding agencies) intend to participate in this call: Austria, Belgium (Flanders and French speaking community), Canada (including Québec), France, Germany, Greece, Hungary, Israel, Italy, Latvia, Poland,Portugal, Romania, Spain, Switzerland, The Netherlands and Turkey.
The aim of the call is to enable scientists in different countries to build an effective collaboration on a common interdisciplinary research project based on complementarities and sharing of expertise, with a clear translational research approach. Projects shall involve a group of rare diseases or a single rare disease following the European definition. For more information, details of the topic, eligibility criteria and timeline go to www.erare.eu


Courses & Educational Initiatives

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

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

European Advanced Postgraduate Course in Classical and Molecular Cytogenetics
Date: February/March of each year
Venue: Nimes, France

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

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

ExPRESS 2015 is the name of the exciting new programme for the upcoming annual EURORDIS Summer School. ExPRESS, which stands for Expert Patients and Researchers EURORDIS Summer School, will gather for the first time both researchers and patient representatives who will be trained together. The trainers are from patient organisations, research institutes and the European Medicines Agency. The four-day training programme develops the capacity of patients' advocates to act as experts in regulatory processes and further their implication in medicines development and advocacy actions both at the national and European levels.
Application Deadline: 31 December, 2014
For further information contact Nancy Hamilton
Visit the EURORDIS website for more information.


What's on Where?

Nerve biology and inherited peripheral neuropathy. From biology to therapy
Date: 11-12 December, 2014
Venue: Madrid, Spain

This International Symposium focuses on current research and development on hereditary neuropathies which are a group of inherited disorders affecting the peripheral nervous system. The symposium boasts of top level researchers and rare disease stakeholders presenting their views.
For further information

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

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

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

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

For further information

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

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

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

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

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

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

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

The First Russian Congenital Aniridia Conference
Date: 3-4 July, 2015
Venue: Salzburg, Austria

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

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

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

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

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


Commercial events

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

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

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

For further information

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

For further information


Media, Press & Publications
Nature Outlook supplement on sickle-cell disease
Nature Outlook has published a series of articles on the current scenario for patients suffering from sickle-cell disease. The articles cover topics that are of current interest to patients suffering from sickle-cell disease such as treatment paradigms, disease management and the socio-political impact of sickle-cell disease. Below are the key ideas presented in the articles of the supplement.

Drug development: A complicated path
In this article the author describes how hydroxycarbamide – the sole FDA approved drug for sickle-cell disease, was discovered and its mode of action. This drug stimulates the production of the foetal form of haemoglobin, which functions like the adult haemoglobin but remains unaffected by the sickle-cell mutation. Many drugs are also designed to combat the acute pain of vaso-occlusive crises, but since this process is multifactorial, the author delineates a combinatorial therapy as a best course of action to reduce pain. Researchers are also investigating other drugs that stimulate foetal haemoglobin, such as pomalidomide, an FDA approved drug used against multiple myeloma, and decitabine, a drug used for a type of bone-marrow cancer. Although there are some promising areas of research the author also keeps the reader abreast of the challenges associated with drug development, especially recruiting patients for clinical trials.

Neurobiology: Life beyond the pain
This is an engaging article on the convoluted, but exciting course of the discovery of trifluoperazine – a widely accepted antipsychotic - for the treatment of sickle-cell disease. The author charts the pathway from when researchers showed that the mouse model of sickle-cell disease, have a reduced level of μ-opioid receptor, also demonstrate temperature insensitivity, which is observed in patients with sickle-cell disease as well. Since temperature is modulated by TRPV1, the author then describes how researchers searched for methods to modulate TRPV1. This is when they discovered that trifluoperazine has the ability to modulate CAMKIIalph, an enzyme that regulates TRPV1, can help sickle-cell disease patients.

Gene therapy: Editorial control
The author of this article talks about the therapeutic potential of gene therapy, namely the use of the zinc finger nucleases (ZFNs), TALENs and CRISPRs (clustered regularly interspaced short palindromic repeats) for patients with sickle-cell disease. Researchers are using these methods for “editing” the genetic makeup of the patients, where haematopoietic stem cells are harvested from patients with sickle-cell disease and then using a viral vector, a new, working haemoglobin gene is inserted into the cells' DNA. Researchers are utilising ZFNs, TALENs as well as the newly introduced, and highly promising CRISPRs, to target the specific region of the faulty DNA.

Perspective: Thinking beyond survival
This article focuses on disease management of patients with sickle-cell disease, as adults with the disease living in the United States may now survive until the fifth decade of their life. Due to this rapid change in mortality in the US there are other challenges that have to be dealt with, such as the long-term health problems that children face due to possibility of suffering a stroke and incurable organ damage. A high risk of brain injury can affect classroom performance as well as future employment opportunities. According the author, these complications, relegate the patient with a “lifelong schedule of annual visits to an array of specialists to ensure appropriate disease management, in addition to regular health check-ups”. The author believes that this demanding schedule, along with financial instability that these patients are often born into, makes it imperative to find ways to improve quality of life, in addition to lessening sickle-cell disease associated events. The authors believe that improving life-expectancy is not the end and conclude that “both biological and non-biological risk factors must be considered collectively if we expect to not only extend the lives of children born with sickle-cell disease, but also improve their quality of life”.

Epidemiology: A moving target
This article describes the how western Europe, east coast of South America, and North America is observing an increase in prevalence of sickle-cell disease, due to migratory activities. The author says that the current number of sickle-cell disease patients is about 100,000 in US and ironically, the increased prevalence is due to better life-expectancy for these patients in US. Also of interest is the study quoted by the author, which states that by 2050, the incidence of sickle-cell disease will increase by 25% (read the article by OrphaNews).

Perspective: We need a global solution
Following the above article, the author addresses the need for a global solution while treating sickle-cell disease. The author indicate expensive lab tests, inability to gain a timely diagnosis as part and parcel of the problems faced by the bulk of sickle-cell patients living in Nigeria, India and the Democratic Republic of Congo. The authors note that from the “sub-Saharan Africa, the Arabian peninsula and the Indian subcontinent, the sickle-cell variant of the haemoglobin gene has spread through the rest of the world”. The author has provided several interesting and workable options that can be adopted to help sickle-cell disease patients all over the world – but especially in low-income countries.

Stem cells: Creating a cure-all
Another treatment approarch that is being widely researched to treat sickle-cell disease patients is the use of stem-cell transplantation. This treatment modality involves obliterating the patients’ bone marrow cells and then inserting fresh new cells which do not carry the sickle-cell mutation. Due to the harshness of this method, current research is attempting to employ gentler techniques, as well as increase the pool of potential donors. The author also highlights studies which are currently underway to be able to perform this technique in utero


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: Divya Unni
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)
Orphanet - All rights reserved
Photo credit : Serimedis http://www.serimedis.inserm.fr/ (unless otherwise stated)