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Germany adopts the National Plan for rare diseases
In keeping with the European Council recommendations, Germany has elaborated and adopted the National Plan for Rare Disease, which will guide and structure actions in rare diseases within their health and social systems. In 2010 the German Federal Ministry of Health (BMG), together with the German Federal Ministry for Education and Research (BMBF) and the Alliance of Chronic Rare Diseases (Allianz Chronisch Seltener Erkrankungen, ACHSE), founded the National Action Coalition for Persons with Rare Diseases (Nationales Aktionsbündnis für Menschen mit Seltenen Erkrankungen, NAMSE). The goal of NAMSE is to improve the quality of life of individuals with a rare disease through a concerted effort. Following a three-year process of coordinating these actions, which involved the commitment of all those involved in the healthcare sector, a total of 52 policy proposals were compiled and included in a National Plan of Action for Persons with Rare Diseases.

The 52 policy proposals in the National plan represent a broad spectrum of tasks to be executed as it addresses the most pressing problems of the patients and their relatives. They include many concrete suggestions on implementing information management, on possible paths to diagnosis, on caretaking structures and on conducting research on rare diseases. The goal of NAMSE is to establish and provide aid to National and European networks of Reference and Expertise Centres that are adapted to the special needs of rare disease patients and make them available to patients and their doctors. This was also highlighted to be in agreement with the cross-border healthcare directive. Adequate funding and certification for these centers will ensure timely diagnoses so patients can receive necessary care. An important goal of the National plan is to intensify the research in the area of rare disease. The National Plan provides vital contribution to the goals of the Framework Program of Healthcare Research presently being pursued by the German Federal Government. Thus funds for research in the field of rare diseases in order to improve diagnosis and treatment are provided in this plan

The successful adoption of this national plan is the result of the hard work and unrelenting engagement of the many experts who participated in the workgroups and of those who were members of the Steering Committee. The publication of the policy proposals is the first big step of the National Action Plan. This will be followed by implementing and monitoring the suggested proposals.
Go to the NAMSE website
For further information


Kay Parkinson-Director and Founder of Alström Syndrome UK (ASUK)
A beacon of courage and spirit, Kay Parkinson has worn many hats during her struggle to help patients suffering from the rare disease- Alström syndrome. Her two children remained un-diagnosed with Alström Syndrome until the age of 15 and 18 and even though faced with unending challenges, she still works tirelessly to provide support for the patients, carers and the professionals working with them. She has recieved wide recognition for her work including the 2013 Eurordis award for “Outstanding Accomplishments in the Field of Rare Diseases”. In an interview with Orphanews Europe, Kay Parkinson describes how she successfully combated the challenges she was confronted with while trying to establish help for patients with Alström syndrome.
Learn more about Alström Syndrome




Orphanews Europe: What motivated you to start this organisation?
Kay Parkinson: Alström Syndrome is a life –limiting disease which in my two children’s case caused childhood blindness, hearing loss, heart failure , diabetes type two, kidney failure, bladder dysfunction and many associated problems. Matthew died aged 25 following heart transplant surgery in 2003 and Charlotte following heart and kidney transplantation in 2010 aged 29.
I founded Alström Syndrome UK charity in 1998 following the late diagnosis of my two children, Matthew was 18 and Charlotte was 15. They had years of mis-diagnosis at my local hospital, before finally being asked to attend Great Ormond Street Hospital as a doctor was looking into their latest diagnosis.

Orphanews Europe: Can you describe the early beginnings of ASUK?
Kay Parkinson: I had studied Law at Exeter University as a mature student, primarily because I was having to fight so many issues for my children and fortunately also specialised in Charity Law.
I informed the Consultant who made the diagnosis that I wanted to start a charity for the condition and she contacted 12 other families she knew with the condition and invited them to our first family conference in 1998. Seven families attended and it soon became clear that even those with a diagnosis were not having all aspects of the disease identified. The following year we invited physicians who were working with my own two children from Torbay Hospital to attend. This was the beginnings of our multi-disciplinary clinics. In a hotel in Brixham, S Devon audiology tests took place in the bedrooms, families gathered round a cardiologist, an endocrinologist and dietician and ad hoc consultations took place wherever they could find a spare room in the hotel. The unmet needs of these families were clear as were the needs of the physicians to see more patients, gain more experience and learn more about the disease. AS UK facilitated and funded this development.
The family conference/clinic progressed on these lines for a number of years. As our numbers grew it became increasingly difficult for families to travel to Torbay and back in a weekend. I was already in touch with Birmingham Children’s Hospital and it was agreed that we could use their facilities at the weekend of our family conference. All was still on an ad hoc voluntary basis with doctors giving freely of their time at the weekends to examine our Alström patients and Alström Syndrome UK charity organising and funding the family conference and the clinic lists.

Orphanews Europe: How did you obtain funding for your charity?
Kay Parkinson: Following Alastair’s talk, Torbay Hospital, Birmingham Children’s Hospital and AS UK decided that we would apply for NHS Commissioning to fund the clinical service on a more professional basis. In 2006 the NHS Commissioning Team for Highly Specialised Services agreed to fund 4 clinics for children at the Birmingham Children’s Hospital yearly and 4 adult clinics at Torbay Hospital. Two outreach clinics in Leeds were also arranged. However, the NHS said at that time that they did not fund charities.
Fortunately my legal training equipped me with the skills to challenge this decision and I set about tracking the legal basis to do this. The COMPACT document signed by Tony Blair when Prime Minister laid out the principles of how the public sector should work with the voluntary sector. Reading the document it became clear that there were a number of breaches in our dealings with the NHS. The NCVO had COMPACT officers funded by the Big Lottery who took up our case. When the breaches were pointed out to the NHS Commissioners, AS UK was invited to meet with them. The outcome was that we were to be funded as equal partners with the two hospitals we worked with in delivering the Alström clinical service that we had developed.

Orphanews Europe: How has ASUK developed since then?
Kay Parkinson: The NHS Commissioned clinics have gone from strength to strength since we started, our numbers have doubled since we incorporated an Asian Mentoring Scheme, the Alström gene has found to be present in a number of families in the Leeds, Bradford area. In 2012 we successfully moved the adult clinic from Torbay Hospital to the brand new state of art Queen Elizabeth Hospital in Birmingham. It had become clear that the needs of our adults could not be met at a district hospital, and although thankful to Torbay for their initial help with setting up the clinics it was time to move on.
On the back of the success of the clinics AS UK applied for and were successful in gaining a Big Lottery Medical and Scientific grant to develop research into the condition through taking skin samples from consenting patients and starting a research database. Cambridge University partnered with AS UK and were commissioned to generate pluripotent stem cells that will be differentiated into cell types. Birmingham and Torbay Hospitals were commissioned to take the skin samples and develop a research database.

Orphanews Europe: Can you describe the challenges you faced while developing this database?
Kay Parkinson: Six months prior to the completion of the grant when AS UK were expecting to be able to review the database, Torbay Hospital announced that AS UK could not have access to it for ethical reasons. As we were not NHS “employees” it was unethical for us to have access and as our patient numbers were so small we would still be able to recognise anonymised data. The fact that we see un-anonymised patient information, as part of our role as a partner in the NHS England, National Specialised Commissioned Alström Clinical Service was ignored. The fact that we owned the database was ignored. This information announced at such a late date in the project put the grant and AS UK into jeopardy. If the Big Lottery were to call back in the grant AS UK would be ruined. Our members had believed that when they consented to the database that AS UK would as owners of the database have access to it.
ASUK kept the Lottery closely informed of discussions and an emergency meeting was held between partners.
The outcome was that the Database will move to the Queen Elizabeth Hospital, Birmingham and all patients will be re-consented to the database explicitly stating that they allow AS UK access. AS UK, will now add further consents to the form; allowing the data to be shared, with EU and International databases.
Alström Syndrome is an ultra-rare condition, the vast majority of patients have been found through the infrastructure and services that I have developed over the years. I instigated, pioneered and fought for the first Alström Syndrome multi-disciplinary clinics in the UK and started the first research through the Big Lottery grant.

Orphanews Europe: What advice would you give to associations that are working for rare disease patients.
Kay Parkinson: I hope the above information helps other groups be more prepared for issues which can arise when working with the NHS and the other groups avoid the problems we encountered.
Patient groups have patient interests at heart- the solutions for rare diseases will only come by all parties to their care bringing down the barriers that prevent collaborative working.
With such a complex condition as Alström it is only the patient groups, families and patients who have lived with all the multiple manifestations of the disease and managed them on a daily basis. We cannot “lock out” their valuable experience and expertise. Patient groups deserve and need better recognition.

Mathew Parkinson (9-2-1978-11-5-2003) and Charlotte Parkinson (11-4-1981- 29-4-2010). The picture was taken in 1998 shortly after diagnosis by Great Ormond Street Hospital. The family was flying to the USA- the only country at that time with any knowledge of the disease. Local press took the photo as they were about to depart.



Call for expressions of interest as Commission appointees to the Commission expert group on rare diseases

The term of office of the members of the European Union Committee of Experts on Rare Diseases expired on 26 July 2013.

Therefore on 30th July the Commission adopted its Decision on setting up a Commission expert group on rare diseases and repealing Decision 2009/872/EC (2013/C 219/04). Read Orphanews Editorial dated 17 Aug 2013

This Decision lays down general rules concerning the criteria and procedure for the designation of the members of this group. The European Commission is now looking to appoint the members of the expert group on rare diseases.

European level patients’ organisations, professional associations, scientific societies and associations producing products or providing services in the field of rare diseases are invited to express their interest and appoint their representatives. N.B. for individuals applying, public health or scientific expertise in the field of rare diseases at EU level is essential.

Both individual experts and other members' representatives should be available for a three year term of office and willing to travel to Luxembourg for regular meetings. Other terms and conditions can be found in the Commission Decision on the setting up of the rare diseases expert group and in the call for expressions of interest.

Once appointed, the expert group will carry out certain tasks in the field of rare diseases requested by the Commission's services. These tasks can include assisting in drawing up guidelines and recommendations, providing advice on implementing EU actions, monitoring, evaluating and disseminating results of EU and national measures, and international cooperation.
To apply click here
Petition requesting amendments to the draft on Data Protection Regulation
A petition addressed to the Rapporteurs of the Draft General Data Protection Regulation in the EU Parliament, the Chairs of the relevant Parliamentary Committees and to the Ministries competent for Justies in the EU Member States is now online.

A considerable amount of research on rare disease depends on the accessibility of data from biobanks and registries. In fact, Member States committed themselves in Council recommendation to consider supporting registries as part of the rare disease national plan. To be able to use the data provided in these registries, it is imperative that there should be some amount of openness regarding data sharing. Data sharing becomes especially important for rare disease research because of the need to go across national borders for increasing sample size of the rare disease patients. The European Parliament’s rapporteur on the Data Protection Regulation has published a draft report endorsing that “...processing of sensitive data for historical, statistical and scientific research purposes is not as urgent or compelling as public health or social protection.” This report is a cause of concern as enacting it into law may make recruiting subjects for clinical research through registries extremely difficult.

Stake holders in the rare disease community which includes researchers, clinicians and patient organisations alike have expressed deep concerns regarding these amendments and have asked to stop this modification of privacy laws. This petition requests amendments to the draft Regulation in favour of health research.
To sign the petition click here



European Medicines Agency releases for public consultation its draft policy on the publication and access to clinical-trial data
The European Medicines Agency has released a draft policy on the publication and access to clinical-trial data for a three-month public consultation. Stakeholders have until 30 September 2013 to send their comments on the draft policy to the Agency.
Read the draft policy on access to clinical trial data



A progress report on rare diseases and orphan drugs policy in Japan

An article published in Expert Opinion Orphan Drugs reports on the current and future policy initiatives on rare diseases in Japan. According to the authors, these initiatives have been an element of the Japanese national health system dated as early as 1972. The authors believe that due to the extensive support from the government, rare disease policy in Japan has witnessed “considerable progress over the past 40 years” which encompasses the orphan drug legislation of 1993.

This legislation not only encouraged research and development of orphan drugs, but also brought changes to the pricing and reimbursement systems. The authors contend that this legislation “facilitated access to orphan drugs, specific research programs to promote research on and development of orphan drugs, and a government-supported information centre to promote the understanding of rare diseases”.

In the article the authors contrast pricing and reimbursement strategies in EU and US, with the Japanese National Health Insurance (NHI) system. Unlike the EU and US, the NHI in Japan “negotiates prices with pharmaceutical companies once a drug is approved for use, allowing a selling price of cost plus 10% for orphan drugs”. Japan has designated130 diseases as intractable or rare diseases, out of which 56 can receive reimbursement of medical expenses. The reimbursement structure allows “30% of expenses paid by insurance companies and the rest paid by national and prefectural governments”.

The authors describe several research programmes that are supported by the Japanese government such as the project establishing ‘Bases for Early and Exploratory Clinical Trials in Specific Research Areas’, launched in 2011 “to promote the development of innovative orphan drugs and medical devices from Japan”. The authors also highlight another project ‘Enhanced International Information Exchange’ launched this year which will aid in “publicis(ing) the results of limited research on rare diseases and orphan drugs to a broader international audience”.

Finally, the authors illustrate the example of Japan Intractable Disease Information Center – a collaborative effort of the MHLW and the Japan Intractable Diseases Research Foundation – to dessiminate information about rare diseases in Japan. The authors highlight that this website gets over 15 million hits per year and is a testament to its in spreading knowledge about rare diseases in Japan
Consult the abstract



Other International News
Change is in the air for sequencing grants
Despite of considerable advances in science and technology, sequencing has not generally entered routine clinical care. Up to now, National Institutes for Health (NIH) grants were difficult to obtain for sequencing. The US National Human Genome Research Institute (NHGRI, part of the National Institutes for Health) is trying to change this situation. It has just announced the second round of Clinical Sequencing Exploratory Research (CSER) grant awardees at four institutions around USA. “These grants aim to answer questions about how genomic sequencing might be used in the treatment of several disorders, and to assess how this information is used by doctors and patients. Each research group must also answer questions about how to generate and communicate the sequence data, and how clinicians and patients cope with the psychosocial and ethical dilemmas this information can present.” explains Lucia Hindorff, programme director for CSER at NHGRI.

Katrina Goddard, a genetic epidemiologist at the Kaiser Permanente Center for Health Research, OR, and a new CSER grantee, along with her colleague Benjamin Wilfond, is showing how genomic sequencing can be used even before a person is born. Sequencing data could be used by couples in order to make more informed choices about carrier status and pregnancy risk for inherited disorders.

Richard Myers’ team from Hudson-Alpha Institute for Biotechnology in Huntsville, will sequence the genomes of 500 children diagnosed with a developmental disorder, as well as both of their parents in order to identify genetic markers common to the disorders and speed up the diagnostic process.

Arul Chinnaiyan’s research group at the University of Michigan, will focus on sarcomas and other rare cancers, sequencing the tumour cells to determine any common genetic alterations in these cancers.

The last research group, is located in the University of Washington and includes Gail Jarvik and Wylie Burke. They will build a coordinating centre, weaving together the various strands of everyone’s research into a large tapestry of data.

Read the full article



Guidance Documents and Recommendations
FIGO COMMITTEE REPORT: Ethical issues in the management of severe congenital anomalies
The FIGO (International Federation of Gynecology and Obstetrics) Committee works making sure ethical aspects of issues that impact the discipline of obstetrics, gynaecology, and women's health are considered. In an article published in the “International Journal of Gynecology and Obstetrics”, the FIGO committee has contributed recommendations for the management of severe congenital abnormalities. According to the committee these recommendations are necessary as “delivering and raising a severely malformed and disabled baby may have an impact on the physical, mental, and social life of a family”.

According to the committee, pre-testing counselling should include a disclosure of the disadvantages and benefits of testing, where the women have the right to detail the information she would like to receive, or not receive. The counselling should also include options for management including termination of pregnancy. They also recommend disclosing sex of the baby for serious sex-linked disorders in countries where sex-determination is illegal and to consider the well-being of the normal foetus in cases of multiple pregnancy. Most importantly the recommendations stress on respecting the right of women to decide whether to continue with the pregnancy. The committee highlights that the recommendations on “Ethical aspects concerning termination of pregnancy following prenatal diagnosis” to be followed for abortions after 22 weeks.
Access the FIGO website

Beta-thalassemia major: an American Heart Association (AHA) consensus statement on cardiovascular function and disease treatment
Consult the Pubmed abstract
To read more about "Beta-thalassemia major"

Circulation ; 128(3):281-308 ; July 2013
Inherited primary arrhythmia syndromes: HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients
Consult Pubmed abstracts
To read more about "Familial long QT syndrome"
To read more about "Brugada syndrome"
To read more about "Catecholaminergic polymorphic ventricular tachycardia"
To read more about "Familial short QT syndrome"
To read more about "Familial progressive cardiac conduction defect"
To read more about "Idiopathic ventricular fibrillation, not Brugada type"

Heart Rhythm ; Epub ahead of print ; June 2013
Europace ; 15(9):1337-82 ; September 2013
Chronic myeloid leukemia: European LeukemiaNet recommendations for 2013
Consult the Pubmed abstract
To read more about "Chronic myeloid leukemia"

Blood ; 122(6):872-84 ; August 2013
Pediatric systemic lupus erythematosus: international consensus for provisions of quality-driven care
Consult the Pubmed abstract
To read more about "Pediatric systemic lupus erythematosus"

Arthritis Care Res (Hoboken). ; Volume 65, Issue 9, pages 1416–1423 ; September 2013


Bioinformatics, Registries and Data Management
Study documents shortcomings of the current International Disease Classifications ICD-10 and SNOMED-CT
In an published in Human Mutation the authors discuss the importance of data sharing and high quality phenotype coding for the understanding of rare disorders and highlight that “the two most widely used coding systems in medicine, ICD-10 and SNOMEDCT, lack information necessary for the detailed classification and annotation of rare and genetic disorders”. The authors emphasise that due to this, there is inefficient registration of such patients in databases which thwarts data-sharing efforts, which is essential for research and care of rare disease patients. The authors compared a new coding system that they developed for metabolic diseases with the help of a “dedicated group of clinical specialists” with those in ICD and SNOMED-CT and found no matches for a staggering 76% of cases in ICD-10 and 54% in SNOMED-CT. This led the authors to conclude that SNOMED-CT and ICD coding systems were grossly deficient for metabolic disorders and also stress that “there may be similar gaps for other classes of rare and genetic disorders”.

The World Health Organization has since taken necessary action to improve ICD-10 for use in the field of rare diseases. Orphanet has recognised the urgent need for “well designed codes for rare diseases” and a Special Topic Advisory Group headed by Dr. Segolene Ayme is assigned with providing advice to the WHO on the current updating and revision process from ICD-10 to ICD-11 on the subject of rare diseases, anticipated to be published in 2015. The authors of this article have also donated the work presented in this article to Orphanet who are working in collaboration with the HPO organizations to improvise the codes for rare diseases in ICD and SNOMED-CT.
Consult the PubMed abstract

ODIN – ORCID and DataCite Interoperability Network

ODIN – ORCID and DataCite Interoperability Network is a two year project which started in September 2012, funded by the European Commission’s ‘Coordination and Support Action’ under the FP7 Programme (Seventh Framework Programme).
ODIN aims to build on the success of ORCID and DataCite initiatives to identify data sets and scientists, and connect them across multiple services and infrastructures for academics, scholars and researchers information sharing and publishing. Its mission is to reduce technical, cultural and logistical barriers to the accessibility, attribution and trust of data.
The issues it will address are the following:
  • Data object referencing
  • Use and re-use tracking
  • Links between a data object, subsets, articles, rights statements and every person involved in its life-cycle
  • Consult ODIN website
    Learn more about ORCID
    Learn more about DataCite


    How rare disease patients/parents are playing different roles to facilitate drug discovery
    An interesting article published in “Drug Discovery Today” emphasises the vital role parents and patients are performing in order to fund, discover and develop treatments for rare and ultra-rare diseases. The article highlights the diverse roles they play and also illustrates some of the success stories that their involvement of has brought about. The diverse roles include entrepreneurial, organizational and in some cases, the role of principal investigators to further scientific knowledge leading to drug discovery. Furthermore, the authors stress that these roles are played by the parent/patients sometimes without any formal education. According to the authors patients/parents make a remarkable “to disrupt the usual course of drug discovery” as the current process usually takes years to find appropriate therapy.

    The authors describe three ultra-rare disease parent/patient advocate groups who are involved in the fast generation of treatment for the diseases and recommend this approach as an alternative model for pharmaceutical research. Their efforts have been instrumental in drug discovery for rare diseases as well as profitability for companies involved in making these drugs. The authors highlight the “urgent need to accelerate discovery and development for thousands of other rare and ultra-rare diseases”. The authors encourage academic and pharmaceutical scientist to come together with the parent and patient advocates to get and give advice for furthering the cause of generating medications for rare disease sooner. However, the authors also warn that a balance is necessary for the patient/parent involvement on when to get involved and when to allow the experts to lead the course. The authors believe that “the lack of formal scientific or medical training should not hold people back in their search for researching or developing treatments”.
    Consult the PubMed abstract

    Study offers a practical approach to management of rare neurological diseases
    An informative article published in Practical Neurology accentuates the frequently observed problem that neurologists are faced with, pertaining to the management of rare neurological diseases using a case report method. The authors believe that this is mainly due to "the lack of generic guidance for the approach to management' which is possibly due to the “complexities with respect to diagnosis, counselling, treatment and monitoring” that are characteristic of rare diseases.

    The authors highlight that patients with rare diseases frequently report frustration with delayed diagnosis or misdiagnosis as well as lack of information and coordinated care. According to a rare disease survey by Rare Diseases UK, 12% of surveyed patients waited for over 10 years for a diagnosis. However the authors believe that diagnosis of rare diseases may be improved and describe a detailed algorithm which includes “recognising well-described physician cognitive errors, the appropriate use of web-based tools such as Orphanet and referral to reference”. The authors also recommend “consider(ing) the available evidence, cost implications of the drug (and any associated monitoring) and adverse effects, as well as patient opinion, before prescribing for rare diseases”. They also highlight that the necessity of open discussion and communication between the neurologist, the patient and general practitioner.
    Consult the PubMed abstract



    IDEAL: international project to explore new methods for design and analysis of clinical studies in rare diseases
    A recently launched research project named IDEAL (Integrated Design and Analysis of small population group trials) will address the urgent need to develop new statistical approaches for efficient evaluation of clinical trials for rare diseases. This project aims to explore new methods for the design and analysis of clinical studies and to formulate an effective strategy for assessing clinical trials for rare diseases. It will collate all available sources of information that will help optimise the process of finding an appropriate statistical method.

    An international research team under the supervision of Professor Ralf-Dieter Hilgers of the Uniklinik RWTH Aachen is supported by the EU Projektmanagement Office der RWTH Aachen. The IDEAL project consists of an advisory board of international experts with diverse professional backgrounds, that represents patient interests, pharmaceutical industry as well as regulatory delegates who will collaborate to develop new designs and sophisticated analysis methods.

    The research has been funded with €3 million by the 7th Framework Programme of the European Union. The work packages focus on “the assessment of randomization, the extrapolation of dose-response information, the study of adaptive trial designs, the development of optimal experimental designs in mixed models, as well as pharmacokinetic and individualized designs, simulation of clinical studies, the involvement and identification of genetic factors, decision-theoretic considerations, as well as the evaluation of biomarkers”.
    Further information on the project



    The Orphanet Mobile app: six months after its release

    The Orphanet mobile application, freely available for iPhone and iPad, gives access to the main Orphanet services without any Internet connection and in 6 languages (English, French, German, Italian, Portuguese and Spanish): access a list of rare diseases with their description and associated resources as epidemiological and coding data (OrphaCode and ICD-10); consult the Emergency guidelines PDFs; find contact details of expert centres and professionals dedicated to rare diseases in the 37 counties of the Orphanet consortium. The application allows bookmarking of favorite pages and PDFs to find them back in one click in the “My Orphanet” section. In addition, pages can be annotated or sent by email.

    Updated every month, the Orphanet application has already been downloaded 4,000 times since its launch on last Rare Disease Day. The second version of the app, providing a dedicated iPad version, was launched in June. This version reached the top10 of apps in the medical area in several countries. The application is getting more and more popular and was warmly welcomed by the professionals and patients.
    Orphanet, the mobile portal for rare diseases - MOBILE HEALTH



    New Research Projects open for Recruitment
    Crowdfunding campaign to help patients with Alkaptonuria: donate now!
    Alkaptonuria, or AKU for short, was the first genetic disease to be discovered more than 110 years ago. Besides the fact that these patients are often faced with misdiagnosis, a lack of efficient care and a lack of awareness, AKU still has no cure. The medical world remains largely unaware of its existence and impact on everyday life. Now more than 100 years later, the drug nitisinone has been identified as the first potential treatment for AKU. Nitisinone is already licensed as a treatment for another rare disease, but it is yet to be approved for treating AKU. The first clinical trial is now almost complete and AKU patients are being sought to participate in the second longer trial. This four year trial to assess the long-term suitability of nitisinone for use in AKU patients, is estimated to begin in late 2013. The trial will be based at three test centres in Europe: Liverpool (UK), Paris (France) and Piestany (Slovakia).

    Help cure Black Bone Disease from bradbell.tv on Vimeo.

    However, the rarity of AKU means patients are scattered around the world. This means that patients from across Europe and beyond have to be recruited to run a good clinical trial. A crowdfunding campaign, initiated by Nick Sireau - father of two boys with AKU, who quit his job to devote his time towards helping AKU patients - aims to generate funds for the clinical trial. The clinical trial needs 140 participants and although this may seem like a small number, for rare disease patients this is an uphill task. By donating money to this crowdfunding campaign you will help them to: Bring patients from across the world to the clinical trial centres. Allow patients to bring carers with them. Help them care for the patients properly while they are on the trial. Allow them to organise events across Europe for patients. The deadline to donate is 17 October 2013.
    Donate now to make a difference for this community .
    Click here to read more about the crowdfunding campaign
    If you are interested in participating in this clinical trial or if you would like more information, please visit
    www.developakure.eu or email the Clinical Trials Coordinator, Hana Ayoob or call +44 (0) 1223 322897




    First description of two siblings homozygous for a 2p21 deletion with a phenotype close to hypotonia-cystinuria syndrome
    In this study, the authors have identified two siblings with a homozygous 2p21 deletion. They displayed a phenotype which was similar to hypotonia-cystinuria syndrome with regard to growth failure and neuro-muscular features, but was characterized by lack of cystinuria. Consult the Pubmed abstract
    Am J Med Genet A. ; 161(8):1853-9 ; August 2013
    Unique TM4SF20 ancestral deletion in 15 unrelated Southeast Asian families with a paediatric disorder of early language delay and cerebral white matter hyper-intensities
    The authors describe here a unique ancestral deletion that segregates with early childhood communication disorders and white matter hyper-intensities in fifteen unrelated families predominantly from Southeast Asia.
    Consult the Pubmed abstract

    Am J Hum Genet. ; 93(2): 197-270 ; August 2013
    SBF1 mutations cause a novel subtype of autosomal recessive demyelinating Charcot-Marie Tooth disease type 4B
    In this study, compound heterozygous missense mutations in SBF1 gene were identified as the underlying cause of a novel subtype of Charcot-Marie Tooth disease in three individuals of a Korean family.
    Consult the Pubmed abstract

    Neurology ; 81(2):165-73 ; July 2013
    New likely MED13L haploinsufficiency syndrome found in two patients with hypotonia, heart defect and intellectual disability
    Using high resolution molecular karyotyping, the authors identified two intragenic de novo frameshift deletions, likely resulting in MED13L haploinsufficiency, in two patients with a similar phenotype of hypotonia, moderate intellectual disability, conotruncal heart defect and facial anomalies.
    Consult the Pubmed abstract

    Eur J Hum Genet. ; Epub ahead of print ; February 2013
    Severe type of autosomal-recessive infantile encephalopathy with epilepsy and dysmorphic corpus callosum caused by biallelic SZT2 mutations in two unrelated children
    In this study, the authors have studied two unrelated children presenting with a distinctive early-onset epileptic encephalopathy, as well as dysmorphic corpus callosum. Using whole-exome sequencing, they identified biallelic mutations in SZT2 in both affected children. They concluded that mutations in SZT2 cause a severe type of autosomal-recessive infantile encephalopathy with intractable seizures and distinct neuroradiological anomalies.
    Consult the Pubmed abstract

    Am J Hum Genet. ; 93(3):524-9 ; September 2013
    Mitochondrial encephalopathy and a disorder of mitochondrial DNA maintenance due to FBXL4 mutations
    In two articles, authors identified mutations in FBXL4 leading to a disorder of mitochondrial DNA maintenance and to mitochondrial encephalopathy onset in early infancy. Consult Pubmed abstracts
    Am J Hum Genet. ; 93(3):471-81 ; September 2013
    Am J Hum Genet. ; 93(3):482-95 ; September 2013



    Rare isolated severe myopia in humans is associated with mutations in LRPAP1 and in SCO2
    Consult Pubmed abstracts
    To read more about "Rare isolated myopia"

    Am J Hum Genet. ; 93(2):313-20 ; August 2013
    Am J Hum Genet. ; 92(5):820-6. ; May 2013
    Autosomal-dominant diffuse non-epidermolytic palmoplantar keratoderma is caused by missense mutations in AQP5
    Consult the Pubmed abstract
    To read more about "Non-epidermolytic palmoplantar keratoderma"

    Am J Hum Genet. ; 93(2):330-5 ; August 2013
    Primary ciliary dyskinesia: ARMC4, ZMYND10, and DYX1C1 mutations found responsible in cases with classic disease, and RSPH1 in 11 families without laterality defects
    Consult Pubmed abstracts
    To read more about "Primary ciliary dyskinesia"

    Am J Hum Genet. ; 93(2):357-67 ; August 2013
    Am J Hum Genet. ; 93(2):336-45 ; August 2013
    Am J Hum Genet. ; 93(2):346-56 ; August 2013
    Nat Genet. ; 45(9):995-1003 ; September 2013
    Am J Hum Genet. ; 93(3):561-70 ; September 2013
    Medullary cystic kidney disease including cardiovascular abnormalities, liver fibrosis and situ inversus is associated with ANKS6 mutations in six families
    Consult the Pubmed abstract
    To read more about "Autosomal recessive medullary cystic kidney disease"

    Nat Genet. ; 45(8):951-6 ; August 2013
    Autosomal-recessive retinitis pigmentosa caused by ARL2BP homozygous mutations
    Consult the Pubmed abstract
    To read more about "Retinitis pigmentosa"

    Am J Hum Genet. ; 93(2):321-9 ; August 2013
    Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency associated with mutations in ELAC2 in five individuals
    Consult the Pubmed abstract
    To read more about "Fatal infantile hypertrophic cardiomyopathy due to mitochondrial complex I deficiency"

    Am J Hum Genet. ; 93(2):211-23 ; August 2013
    Phacomatosis pigmentokeratotica is caused by a postzygotic HRAS mutation in a multipotent progenitor cell
    Consult the Pubmed abstract
    To read more about "Phakomatosis pigmentokeratotica"

    J Invest Dermatol. ; 133(8):1998-2003 ; August 2013
    Autosomal dominant Dandy-Walker malformation and occipital cephaloceles: identification of mutations in extracellular matrix genes NID1 and LAMC1
    Consult the Pubmed abstract
    Hum Mutat. ; 34(8):1075-9 ; August 2013
    Pilocytic astrocytoma: whole-genome sequencing identified recurrent somatic alterations of FGFR1 and NTRK2
    Consult the Pubmed abstract
    To read more about "Pilocytic astrocytoma"

    Nat Genet. ; 45(8):927-32 ; August 2013
    ACTH-independent macronodular adrenal hyperplasia: somatic mutation in EDNRA could be implicated
    Consult the Pubmed abstract
    To read more about "ACTH-independent macronodular adrenal hyperplasia"

    Fam Cancer. ; Epub ahead of print ; June 2013
    Idiopathic and/or familial pulmonary arterial hypertension: novel heterozygous missense variant in KCNK3 as a disease-causing candidate gene
    Consult the Pubmed abstract
    To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

    N Engl J Med. ; 369(4):351-61 ; July 2013
    Isolated CoQ-cytochrome C reductase deficiency caused by mutations in CYC1 in two unrelated children
    Consult the Pubmed abstract
    To read more about "Isolated CoQ-cytochrome C reductase deficiency"

    Am J Hum Genet. ; 93(2) : 384-389, ; August 2013
    Familial thoracic aortic aneurysm and aortic dissection: identification of the same rare variant PRKG1 in four families
    Consult the Pubmed abstract
    To read more about "Familial thoracic aortic aneurysm and aortic dissection"

    Am J Hum Genet. ; 93(2): 398-404 ; August 2013
    Short rib-polydactyly syndrome and Jeune syndrome associated with heterozygous mutations in WDR60
    Consult the Pubmed abstract
    To read more about "Short rib-polydactyly syndrome, Verma-Naumoff type"
    To read more about "Jeune syndrome"
    To read more about "Short rib-polydactyly syndrome"

    Am J Hum Genet ; 93(3):515-23 ; September 2013
    A vascular-anomaly syndrome with phenotypic overlap with Rendu-Osler-Weber disease caused by BMP9 mutations in three unrelated individuals
    Consult the Pubmed abstract
    To read more about "Hereditary hemorrhagic telangiectasia"

    Am J Hum Genet. ; 93(3):530-7 ; September 2013
    Oral-facial-digital syndrome: exome-sequencing revealed a different homozygous variant in DDX59 in two multiplex consanguineous Arab families
    Consult the Pubmed abstract
    To read more about "Oral-facial-digital syndrome"

    Am J Hum Genet. ; 93(3):555-60 ; September 2013
    Early infantile epileptic encephalopathy: de novo heterozygous mutations identified in GNAO1 in four individuals
    Consult the Pubmed abstract
    To read more about "Early infantile epileptic encephalopathy"

    Am J Hum Genet. ; 93(3):496-505 ; September 2013
    Autosomal-recessive hypocomplementemic urticarial vasculitis associated with DNASE1L3 mutations in two families
    Consult the Pubmed abstract
    To read more about "Hypocomplementemic urticarial vasculitis"

    Arthritis Rheum. ; 65(8):2183-9 ; August 2013
    Isolated spina bifida: potential role of NKX2-8 as a genetic component of neural tube defects
    Consult the Pubmed abstract
    To read more about "Isolated spina bifida"

    PLoS Genet. ; 9(7):e1003646 ; July 2013
    Wegener granulomatosis: HLA-DP and SEMA6A identified as contributors to risk for the disease
    Consult the Pubmed abstract
    To read more about "Granulomatosis with polyangiitis"

    Arthritis Rheum. ; 65(9):2457-68 ; September 2013





    Clinical Research
    Fragile X syndrome: high MMP-9 activity levels were lowered by minocycline and a majority of children were improved by a 3-month minocycline treatment
    Consult Pubmed abstracts
    To read more about "Fragile X syndrome"

    Am J Med Genet A. ; 161(8):1897-903 ; August 2013
    J Dev Behav Pediatr. ; 34(3):147-55 ; April 2013
    Patients with Loeys-Dietz syndrome type 1 present increased fracture risk and low bone mineral density
    Consult the Pubmed abstract
    To read more about "Loeys-Dietz syndrome type 1"

    Am J Med Genet A. ; 161(8):1910-4 ; August 2013
    Pulmonary hypertension: modest improvements with riociguat in exercise capacity and pulmonary vascular resistance
    Consult Pubmed abstracts
    Consult these studies on Orphanet
    Consult these studies on Orphanet

    To read more about "Chronic thromboembolic pulmonary hypertension"
    To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

    N Engl J Med. ; 25;369(4):319-29, 330-40 ; July 2013
    Wegener granulomatosis and microscopic polyangiitis: a single course of rituximab is as effective as continuous conventional immunosuppressive therapy
    Consult the Pubmed abstract
    Consult this study on Orphanet

    To read more about "Granulomatosis with polyangiitis"
    To read more about "Microscopic polyangiitis"

    N Engl J Med. ; 369(5):417-27 ; August 2013
    Mantle cell lymphoma: ibrutinib shows durable single-agent efficacy in relapsed or refractory disease
    Consult the Pubmed abstract
    To read more about "Mantle cell lymphoma"

    N Engl J Med. ; 369(6):507-16 ; August 2013
    Patients with high-risk hepatoblastoma: SIOPEL-4 treatment regimen (cisplatin and surgery) is feasible and efficacious for complete remission at the end of treatment
    Consult the Pubmed abstract
    Consult this study on Orphanet

    To read more about "Hepatoblastoma"

    Lancet Oncol. ; 14(9):834-42 ; August 2013
    Glioblastoma: adenovirus-mediated gene therapy with sitimagene ceradenovec followed by intravenous ganciclovir does not improve overall survival
    Consult the Pubmed abstract
    To read more about "Glioblastoma"

    Lancet Oncol. ; 14(9):823-33 ; August 2013
    Refractory or recurrent non-testicular malignant germ-cell tumor: a multimodal strategy integrating regional deep hyperthermia might be a successful treatment option
    Consult the Pubmed abstract
    To read more about "Germ cell tumor"

    Lancet Oncol. ; 14(9):843-52 ; August 2013
    Cornelia de Lange syndrome: identification of high frequency of antibody deficiency
    Consult the Pubmed abstract
    To read more about "Cornelia de Lange syndrome"

    Pediatrics. ; 132(2):e484-9 ; August 2013
    Women who conceived after a diagnosis of vasculitis had a higher rate of pregnancy loss than those who conceived prior to diagnosis
    Consult the Pubmed abstract
    To read more about "Granulomatosis with polyangiitis"
    To read more about "Microscopic polyangiitis"
    To read more about "Polyarteritis nodosa"
    To read more about "Behçet disease"
    To read more about "Takayasu arteritis"
    To read more about "Eosinophilic granulomatosis with polyangiitis"

    Arthritis Care Res (Hoboken). ; 65(8):1370-4 ; August 2013
    Pregnancy in patients with Behcet disease does not appear to be associated with an increased rate of pregnancy-related complications
    Consult the Pubmed abstract
    To read more about "Behçet disease"

    Arthritis Rheum. ; 65(9):2450-2456 ; September 2013


    Stem Cells
    Congenital stationary night blindness: photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina
    Consult the Pubmed abstract
    To read more about "Congenital stationary night blindness"

    Nat Biotechnol. ; 31(8):741-7 ; August 2013


    Gene Therapy

    Mucopolysaccharidosis type 3: intracerebrospinal fluid gene therapy corrects both central nervous system and somatic pathology in a mouse model
    Consult the Pubmed abstract
    To read more about "Mucopolysaccharidosis type 3"
    To read more about "Sanfilippo syndrome type A"

    J Clin Invest. ; 123(8): 3254–3271 ; August 2013
    Sickle cell anemia: β-globin gene transfer improves physiological parameters
    Consult the Pubmed abstract
    To read more about "Sickle cell anemia"

    J Clin Invest. ; Epub ahead of print ; July 2013
    Argininemia: AAV-based gene therapy prevents neuropathology and results in normal cognitive development in the hyperargininemic mouse
    Consult the Pubmed abstract
    To read more about "Argininemia"

    Gene Ther. ; 20(8):785-96 ; August 2013
    Usher syndrome type 1: MYO7A therapy with AAV2 or AAV5 single vectors is efficacious
    Consult the Pubmed abstract
    To read more about "Usher syndrome type 1"
    To read more about "Usher syndrome"

    Gene Ther. ; 20(8):824-33 ; August 2013
    Idiopathic and/or familial pulmonary arterial hypertension: therapeutic efficacy of AAV1.SERCA2a in a rat model
    Consult the Pubmed abstract
    To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

    Circulation ; 128(5):512-23 ; July 2013


    Therapeutic Approaches

    Glioblastoma: multifaceted oncolytic virus therapy in an immunocompetent cancer stem cell murine model
    Consult the Pubmed abstract
    To read more about "Glioblastoma"

    Proc Natl Acad Sci U S A. ; 110(29):12006-11 ; July 2013
    Correction of classical homocystinuria in mice by treatment with proteasome inhibitors
    Consult the Pubmed abstract
    To read more about "Classical homocystinuria"

    Hum Mutat. ; 34(8):1085-93 ; August 2013
    X-linked adrenoleukodystrophy: pioglitazone halts axonal degeneration in a mouse model
    Consult the Pubmed abstract
    To read more about "X-linked adrenoleukodystrophy"

    Rett syndrome: statin drugs improve systemic perturbations of lipid metabolism, alleviate motor symptoms and confer increased longevity in Mecp2 mutant mice
    Consult the Pubmed abstract
    To read more about "Rett syndrome"

    Nat Genet. ; 45(9):1013-20 ; August 2013
    Frontotemporal dementia and amyotrophic lateral sclerosis: CDC7 as a novel therapeutic target for TDP-43 proteinopathies
    Consult the Pubmed abstract
    To read more about "Frontotemporal dementia"
    To read more about "Amyotrophic lateral sclerosis"

    Ann Neurol. ; Volume 74, Issue 1, pages 39–52 ; July 2013
    Proximal spinal muscular atrophy: celecoxib increases SMN and survival in a mouse model via p38 pathway activation
    Consult the Pubmed abstract
    To read more about "Proximal spinal muscular atrophy"

    Hum Mol Genet. ; 22(17):3415-24 ; September 2013
    Idiopathic and/or familial pulmonary arterial hypertension: low-dose FK506 (tacrolimus) could be useful in the treatment of this disease
    Consult the Pubmed abstract
    To read more about "Idiopathic and/or familial pulmonary arterial hypertension"

    J Clin Invest. ; 123(8):3600-13 ; August 2013
    Pulmonary hypertension: beneficial effects of dehydroepiandrosterone in a rodent model of infantile disease
    Consult the Pubmed abstract
    To read more about "Idiopathic and/or familial pulmonary arterial hypertension"
    To read more about "Pulmonary arterial hypertension associated with congenital heart disease"
    To read more about "Pulmonary hypertension owing to lung disease and/or hypoxia"

    Pediatr Res. ; 74(2):163-9 ; August 2013
    Glioblastoma: systemic delivery of saposin C-dioleoylphosphatidylserine has antiangiogenic and antitumor effects
    Consult the Pubmed abstract
    To read more about "Glioblastoma"

    Mol Ther. ; 21(8):1517-25 ; August 2013
    Neuroblastoma with MYCN amplification: small molecule inhibitors of Aurora-A induce proteasomal degradation of N-Myc and tumor regression and prolonged survival in a mouse model
    Consult the Pubmed abstract
    To read more about "Neuroblastoma"

    Cancer Cell ; 24(1):75-89 ; June 2013
    Hereditary chronic or autoimmune pancreatitis: treatment with siRNA resolved pancreatic fibrosis and suppressed tissue hydroxyproline levels in rats
    Consult the Pubmed abstract
    To read more about "Hereditary chronic pancreatitis"
    To read more about "Autoimmune pancreatitis"

    Gut ; 62(9):1328-39 ; September 2013
    Tubacin could be used in the future in utero to prevent neuronal migration defects and epileptic activity caused by Srpx2 silencing
    Consult the Pubmed abstract
    To read more about "Rolandic epilepsy - speech dyspraxia"
    To read more about "Bilateral perisylvian polymicrogyria"

    Brain ; 136(Pt 8):2457-73 ; August 2013


    Diagnostic Approaches
    Primary progressive aphasia: a brief speech expression protocol aids in the differential diagnosis of the three principal forms
    Consult the Pubmed abstract
    To read more about "Primary progressive aphasia"
    To read more about "Logopenic progressive aphasia"
    To read more about "Progressive non-fluent aphasia"
    To read more about "Semantic dementia"

    Neurology ; 81(4):329-36 ; July 2013


    Primary ciliary dyskinesia: overcoming challenges and recent advances in diagnostics, genetics and characterization of clinical disease
    Consult Pubmed abstracts
    To read more about "Primary ciliary dyskinesia"

    Am J Respir Crit Care Med. ; Epub ahead of print ; June 2013
    Paediatr Respir Rev. ; Epub ahead of print ; June 2013
    Rev Pneumol Clin. ; 69(4):217-24 ; August 2013
    Review on Epstein-Barr virus-positive diffuse large B cell lymphoma of the elderly
    Consult the Pubmed abstract
    To read more about "Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly"
    To read more about "Diffuse large B-cell lymphoma"

    Blood. ; 122(3):328-40. ; July 2013
    West-Nile encephalitis: review of the literature
    Consult the Pubmed abstract
    To read more about "West-Nile encephalitis"

    JAMA. ; 310(3):308-15 ; July 2013
    Ten rare tumors that warrant a genetics referral
    Consult the Pubmed abstract
    To read more about "Adrenocortical carcinoma"
    To read more about "Endocrine tumor"
    To read more about "Familial gastric cancer"
    To read more about "Primary peritoneal carcinoma"
    To read more about "Familial leiomyomatosis"
    To read more about "Hereditary nonpolyposis colon cancer"
    To read more about "Medullary thyroid carcinoma"
    To read more about "Hereditary pheochromocytoma-paraganglioma"
    To read more about "Familial renal cell carcinoma"
    To read more about "Peutz-Jeghers syndrome"

    Fam Cancer. ; 12(1):1-18 ; March 2013
    Costello syndrome: orthopedic management should be part of routine medical care, with screening of spinal deformity and hip dysplasia
    Consult the Pubmed abstract
    To read more about "Costello syndrome"

    Am J Med Genet A. ; 161(8):1940-9 ; August 2013
    Friedreich ataxia: increased prevalence of sleep-disordered breathing
    Consult the Pubmed abstract
    To read more about "Friedreich ataxia"

    Neurology ; 81(1):46-51 ; July 2013
    Joubert syndrome: review on the clinical range, the genetic basis, the overlap with other ciliopathies and the evidence supporting oligogenic inheritance
    Consult the Pubmed abstract
    To read more about "Joubert syndrome and related disorders"

    Lancet Neurol ; 12(9):894-905 ; September 2013
    Toxic epidermal necrolysis: history, classification, clinical features, diagnosis and treatment
    Consult Pubmed abstracts
    To read more about "Toxic epidermal necrolysis"
    To read more about "Lyell syndrome"
    To read more about "Stevens-Johnson syndrome"

    J Am Acad Dermatol. ; 69(2):173.e1-173.e13; 69(2):187.e1-187 ; August 2013
    Huntington’s disease: overview of the disease and of Huntington’s disease-like syndromes
    Consult the Pubmed abstract
    To read more about "Huntington disease"
    To read more about "Huntington disease-like syndrome"

    Curr Opin Neurol. ; 26(4):420-7 ; August 2013
    Neurological complications of dengue fever
    Consult the Pubmed abstract
    To read more about "Dengue fever"

    Lancet Neurol. ; 12(9):906-19 ; September 2013


    More efficient delivery of orphan medicinal products in less market-based countries
    Orphan Drug legislations have been enacted in several countries to provide incentives for manufacturers to create new orphan drugs. These incentives have proved to be beneficial to many companies who have incurred substantial profits. However, according to the authors of an article published in Therapeutic Innovation & Regulatory Science, the adoption and success of orphan drugs is greatly dependent on the market forces of countries and “these incentives directly and indirectly affect orphan drug markets and contribute to classifying a country as being more or less market based”. Countries such as the US are considered market-based as they follow free market principles with limited governmental regulation, dictated by supply, demand, and pricing. Less market-based economies depend less on free market principles, which according to the authors are more beneficial for the adoption of orphan drugs.

    The authors analysed “orphan drug adoption of 13 marketed orphan drugs in France, Germany, Spain, the UK, and the US”, which revealed a “statistically significant but negative relationship between the degree to which a country is market based and the adoption of orphan drugs”. The study concludes that less market-based countries with regulations supporting orphan drug production lead to "a more efficient delivery of orphan drug products to patients with rare diseases". The authors believe the study’s results to be “unsurprising” given that orphan drug legislations encourage research and development of orphan medicinal products to incentivise its production due to which the orphan drug markets behave differently from non–orphan drug markets. .
    Consult the abstract



    Political and Scientific News
    Analysing cost-effectiveness of Orphan Drugs: suggestions for the future
    This month in the article published in Applied Health Economics and Health Policy, authors discuss several approaches to tackle the decision of the Dutch Healthcare Insurance Board advice on not reimbursing orphan drugs (enzyme replacement therapy) that target lysosomal storage disorders: agalsidase alfa and agalsidase beta for Fabry disease and alglucosidase alfa for Pompe disease. The Dutch Healthcare Insurance Board concluded this on the basis of the “unfavourable cost effectiveness originated from the limited additional therapeutic value (as a result of the slow progression of the disease) and high costs”. Additionally continued reimbursement of these drugs would lead to limited resources for other drugs which may be more cost-effective.

    Reimbursement of drugs based on cost-effectiveness has been a topic of intense debate due to scientific as well as political challenges. According to the authors, cost-effectiveness concerns of orphan drugs is due to in the inherent uncertainty around its the safety and effectiveness at the time of market launch owing to small number of clinical trial subjects, the lack of randomized controlled trials, and the use of surrogate efficacy measures. The authors believe that the need of times is for proper guidelines on analysing and assessing cost effectiveness of orphan drugs for (ultra-)rare diseases like the National Institute for Health and Clinical Excellence (NICE) who are responsible for assessing orphan drugs in England and Wales from April 2013.

    To address the issue of low numbers of patients in the Netherlands, the proposed launch of a “compulsory European wide registry following marketing authorization of an orphan drug” is encouraged by the authors. According to the authors addressing economic evaluation will involve approaches such as “variable cost-effectiveness thresholds (which would set a higher threshold for orphan drugs) or weighted cost-effectiveness ratios (where the health gain in a patient with a rare disease would receive a higher weight)”. They recommend further research to unravel societal values about orphan drugs and then incorporate this in the decision-making process.
    Access the article

    Review of 11 orphan drugs reveals scope for studying cost-effectiveness
    Authors of a study published in Orphanet Journal of Rare Diseases address a question similar to the previous article by systematically reviewing the available evidence on clinical effectiveness, cost-effectiveness and budget impact for orphan drugs. The authors analysed 338 studies recieved on PubMed, Embase, NHS EED and HTA databases for 11 inpatient orphan drugs listed on the Dutch policy rule on orphan drugs. The authors analysed a total of that met the inclusion criteria for this study. According to the authors, 96% of the studies focused on clinical effectiveness of the drug, of which 41% were case studies while 39% observational studies.

    However, the authors observed that for all orphan diseases at least one experimental or quasi-experimental study was found, and a randomized clinical trial (RCT) was available for more than half of the orphan drugs studied where eight studies described the cost-effectiveness of an orphan drug and an equal number described an orphan drug’s budget impact. The authors therefore debunk the often heard claim that RCTs are not feasible for orphan drugs, as they found that an RCT was available in 60% of orphan drugs investigated.

    The authors highlight that since cost-effectiveness and budget impact analyses for orphan drugs are seldom published, assessing the effectiveness of orphan drugs, policy makers should expect an international interventional study to be available. They also inform policy makers to not expect country-specific RCTs to have been carried out and assessing the cost-effectiveness and budget impact of treatments, policy makers should not expect to find large body of evidence in the literature. The authors recognise that policy makers are restricted to evidence submitted by pharmaceutical companies or to coverage-with-evidence-development schemes and whether the available evidence is considered to be sufficient fully depend on the role of evidence based medicine in reimbursement decisions. The authors strongly urge further research is needed to examine the relation between available evidence and positive reimbursement decisions.
    Read the Open Access article




    SMA Europe announces its 6th international Call for SMA Research Projects
    This new Call for SMA Projects will be open to any research project aimed at finding a therapy for Spinal Muscular Atrophy (SMA) or at elucidating the basic pathophysiological processes of the disease. The overall goal of SMA Europe is to help the dedicated international scientific and medical community in its search for therapies for SMA. Time being critical for people with SMA, preferences will be given to projects that have the greatest potential to overcome barriers to translation of advances in basic science and to accelerate the identification of effective treatments. For more information please visit the SMA Europe web site


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

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

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

    Further Information about this course can be found on the epirare website For further details

    European Cytogeneticists Association Courses
    The European Advanced Postgraduate Course in Classical and Molecular Cytogenetics 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. Information for the 2014 course is now available. For Further details
    1st Asia Pacific Inborn Errors of Metabolism course
    Date: 09-11 January 2014
    Venue: Tokyo, Japan

    The 1st Asia Pacific Inborn Errors of Metabolism course is aimed at clinicians with a basic knowledge of inborn errors of metabolism who are training or working in this field. Both adult and childhood disease will be covered so it is suitable for practitioners in both areas. This course is intended to be interactive; it brings together a vast array of know-how, experts and resources to improve participants understanding of IEM in order to promote best practice in hospitals and healthcare systems For more information and to register (before November 20th), please visit www.orphan-europe-academy.com

    Orphan-product-designation and -grant workshop
    Date: 4 October 2013
    Venue: Maryland, USA

    Registration is open for the orphan-product-designation and -grant workshop. Organised by the United States Food and Drug Administration (FDA), the aim of the workshop is to provide information on the European Medicines Agency (EMA) and FDA programmes for orphan-medicinal-product designation, as well as on the FDA programmes for orphan-product grants and humanitarian-use device designation to pharmaceutical, biotechnology and device companies, as well as to academics.
    For further information




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

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

    16th International Conference on Behçet's Disease
    Date: 18-20 September 2013
    Venue: Paris, France

    the Conference will provide high quality contributions on a wide range of topics including clinical innovations, genetics and basic science. Update on new therapeutic strategies will be presented and challenging issues will be discussed. We have planned to invite distinguished lecturers notably in the field of innate immunity.
    For further details

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

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

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

    Organised by Finnish Rare Diseases Alliance (HARSO)
    For further details go to http://www.harsofinland.net

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

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

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

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

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

    2nd International Expert Meeting on Congenital Melanocytic Nevi and Neurocutaneous Melanocytosis
    Date: 28-30 September 2013
    Venue: Marseille, France

    This conference aims to report results and observations on Congenital Melanocytic Nevi and Neurocutaneous Melanocytic and paediatric melanoma as well as report to the medical and scientific community on the availability and development of patient-managed research resources. The conference also aims to incorporate various patient groups into a newly formed international federation.
    For further details

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

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

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

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

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

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

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

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

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

    Orphan Drug & Rare Disease Seminar “Accelerating access to therapeutic innovation”
    Date: 17-18 October 2013
    Venue: Marseille; France

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

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

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

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

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

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

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

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

    Organised by HUFERDIS; Hungarian Federation of People with Rare and Congenital Diseases
    For further details go to www.rirosz.hu

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

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

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

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

    Organised by Ministry of Health

    EUROPLAN National Conferences Netherlands
    Date: 14-15 November 2013
    Venue: Netherlands

    Organised by VSOP; the Dutch Genetic Alliance
    For further details go to http://www.vsop.nl

    5th European Symposium on Rare Anaemias
    Date: 15-16 November 2013
    Venue: Ferrara, Italy

    The 5th European Symposium on Rare Anaemias is an activity within ENERCA project to disseminate and up-to-date knowledge on rare anaemias and, at the same time, increase their awareness. An integrated in the framework of the 5th European Symposium on Rare Anaemias, the three organizers (ENERCA, UNITED and TIF) have collaborated in setting up the 1st Italian Thalassaemia meeting for patients and health professionals in Ferrara.
    For further details

    The 8th ICORD Meeting
    Date: 1-2 November 2013
    Venue: St Petersburg, Russia

    The annual ICORD conference gathers representatives of government, academia, patients organisations. An opportunity for collaboration for patients, researchers, seekers of new projects and products and advocates for those affected by rare diseases.
    For further details

    EUROPLAN National Conferences Italy
    Date: 15-16 November 2013
    Venue: Rome, Italy


    Explaining the Price of Orphan Drugs
    Date: 14-15 November 2013
    Venue: Geneva, Switzerland

    This commercial event will bring together orphan drug developers, European payers and HTA experts to shape industry understanding on orphan drug pricing and create stakeholder alignment when discussing the value of an orphan drug. br>For Further Information

    EUROPLAN National Conferences Luxembourg
    Date: 19-20 November 2013
    Venue: Luxembourg

    Organised by Luxembourg Alliance for Rare Diseases and Neuro Muscular Diseases (ALAN)
    For further details go to www.alan.lu/alan

    EUROPLAN National Conferences Serbia
    Date: 5-6 December 2013
    Venue: Belgrade, Serbia

    Organised by NORBS; Serbian National Organization for Rare Diseases
    For further details go to www.norbs.rs>

    EUROPLAN National Conferences France
    Date: 13 January 2014
    Venue: Paris, France

    Organised by Alliance Maladies Rares
    For further details go to www.alliance-maladies-rares.org

    EUROPLAN National Conferences Spain
    Date: 24 January 2014
    Venue: Burgos, Spain

    Organised by FEDER; the Spanish Alliance for Rare Diseases
    For further details go to www.enfermedades-raras.org

    EUROPLAN National Conferences Ireland
    Date: February 2014
    Venue: Dublin, Ireland

    Organised by GRDO, Genetic and Rare Disorders Organisation
    For further details go to www.grdo.ie>

    EUROPLAN National Conferences Belgium
    Date: 28 February 2014
    Venue: Brussels, Belgium

    Organised by Belgian National Alliance for Rare Diseases
    For further details go to radiorg.be>

    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. There is presently no known cure for Batten disease

    19th Congress of the European Association of Hospital Pharmacists
    Date: 26-28 March 2014
    Venue: Barcelona, Spain

    For further details




    Familial Cancer
    Volume 12, Issue 2, June 2013 dedicated to Lynch syndrome: Table of content page 1 Table of content page 2
    Review on primary antibody deficiencies
    Consult the Pubmed abstract

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

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

    Orphanet Partner Country Representatives: 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), Zsuzsanna Lengyel (Hungary), Andrew Green (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)
    For more information on the European Union Committee of Experts on Rare Diseases
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