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The orphans have been adopted! The EU rare disease recommendation passes under Czech EU Council Presidency

For a while it seemed touch-and-go. The latter stages of the process leading toward the adoption of a Council Recommendation on an Action in the Field of Rare Diseases were besieged by challenges. Stakeholders were already holding their breath through the complex and time-consuming Parliamentary elections, and before they could relax again, the sudden and unexpected outbreak of the A/H1N1 virus occurred - a phenomenon that could easily have toppled the Council Recommendation from the European Council agenda. Would the final adoption by the Council of Ministers have to be postponed until the Swedish term of the EU presidency?

In fact, perserverance of the committed Czech team which was behind all negotiations ensured that the adoption procedure stuck the course and appeared on the Council of Ministers agenda on its scheduled date of 9 June 2009. At the 2947th Council session of the European Union (Employment, Social Policy, Health and Consumer Affairs) taking place under the Presidency of Mr Petr Šimerka, Minister of Labour and Social Affairs, Mr Michael Kocab, Minister for Human Rights and National Minorities, and Ms Dana Juraskova, Minister of Health of the Czech Republic, the final adoption of the Council Recommendation on an Action in the Field of Rare Diseases took place.

Of the many players who contributed to the passage of the precious text that delineates a strategy of action for the EU Member States (MS), one person in particular worked hard in the final stages to ensure that adoption of the Recommendation went through on schedule during the term of the Czech Republic EU presidency. Professor Milan Macek Jr., Chairman of the Institute of Biology and Medical Genetics, Charles University-2, School of Medicine Prague, and the key advisor the Sector Agenda for Rare Diseases under the Czech EU Presidency, toiled incessantly to ensure that the momentum did not get derailed.

Up to the final moment of adoption, the possibility of discord amongst the Council Ministers threatened to hinder the process. The challenge, commented Prof. Macek, lay in “…trying to reconcile the conflicting views on the role of government in regulating healthcare, together with balancing the principle of national “subsidiarity” with EU-wide principles in this area .” These differences, he explained, are a “reflection of the rich cultural diversity across Europe.” He defined one principal challenge of the Council Ministers meeting as “keeping the focus on the crucial elements of the Recommendation”. Despite different perspectives, the final document was adopted unanimously. The Recommendation sets out twenty specific recommendations gathered into seven main strategic areas:

  • I. Plans and strategies in the field of rare diseases – calls on the MS to elaborate and adopt a plan or strategy by the end of 2013.
  • II. Adequate definition, codification and inventorying of rare diseases – evokes the common definition of a rare disease as a condition affecting no more than 5 per 10 000 persons; aims to ensure that rare diseases are adequately coded and traceable in all health information systems based on the ICD and in respect of national procedures; and encourages MS to contribute actively to the inventory of rare diseases based on the Orphanet network.
  • III. Research on rare diseases – calls for the identification and fostering of rare disease research at all levels.
  • IV. Centres of expertise and European reference networks for rare diseases – asks the MS to identify and facilitate networks of expertise based on a multidisciplinary approach to care, and foster the diffusion and mobility of expertise and knowledge.
  • V. Gathering the expertise on rare diseases at European level - MS should share best practices, develop medical training relevant to the diagnosis and management of rare diseases, coordinate European guidelines, and, to minimise the delay in access to orphan drugs, MS should share clinical/therapeutic added-value assessment reports at the Community level.
  • VI. Empowerment of patient organisations - the MS should consult patient representatives on policy development; facilitate patient access to updated information on rare diseases; promote patient organisation activities.
  • VII. Sustainability – long-term sustainability in the field of information, research and healthcare of infrastructures must be ensured.

  • The adoption of the Council Recommendation on rare diseases is being celebrated as the final hurdle successfully cleared toward a cohesive harmonised approach to rare diseases across Europe. The original Communication on European Action in the Field of Rare Diseases, entitled Rare Diseases: Europe’s Challenges, was drafted by the European Commission in close collaboration with the Rare Disease Task Force between June and October 2007. The document opened for public consultation in mid-November. Readers may recall that the public consultation to the Communication garnered an unprecedented number of responses: Almost 600 contributions were received from 15 MS during the three-month consultation period, outdistancing the previous contender for most responses by over 400 comments. (The average number of responses to a consultation is 60). This overwhelming reaction was taken as a sign of proof of the pertinence of the Communication on Rare Diseases and the desire across Europe to see its provisions implemented in the near future. The comments received were consulted and the document was adapted accordingly. Next, the Communication was subject to an impact assessment that studied the political and financial consequences, amongst other considerations, between March and June 2008. It then went for an inter-service consultation from July 2008 through October 2008 involving DG Enterprise, DG Research, DG Information and Society, DG Budget, DG Employment, DG Relex, DG Market and the legal service of the European Commission. Finally, on 11 November 2008, the Communication on rare diseases was adopted via oral procedure, by the college of Commissioners, along with a proposal for a European Council Recommendation on a European action in the field of rare diseases. Then, earlier this year, the European Parliament and the European Social and Economic Committee issued opinions on the Proposal for a Council Recommendation, overwhelmingly supporting the contents of the crucial document. The amendments issued during this process were incorporated into the final text adopted on 9 June by the European Council of Ministers - a body that serves to define the general political guidelines of the European Union and is the main decision-making agent. Every Council meeting is attended by one minister from each EU country. For the meeting on the rare disease Recommendation, it was typically the ministers of health who attended.

    Some countries already have national rare disease plans in place. France was the first country to implement a national plan specifically for rare diseases; Bulgaria and Portugal have since followed suit. Other MS are in the midst of defining strategies for rare disease research, diagnostics, treatments, and care. And still other countries are gathering momentum and expertise to launch the process. The Irish Times, for example, ran a news article in response to the adoption of the Council Recommendation, calling for a national plan for the country. OrphaNews Europe intends to follow very closely the actions of each EU Member State on fulfilling specifications of the Council Recommendation.
    View the Council Recommendation (available in 22 EU languages)

    Spotlight on...
    Rare diseases in the Czech Republic
    The Council Recommendation for a European Action in the Field of Rare Diseases was pushed through to its final adoption earlier this month under the EU Presidency of the Czech Republic. Professor Milan Macek Jr., Chairman of the Institute of Biology and Medical Genetics, Charles University Prague-2 School of Medicine, was involved as a key advisor to the Sector Agenda for Rare Diseases during the Czech EU Presidency.

    The birthplace of mendelian genetics
    It seems only right that the Czech Republic would oversee the final important stage of the Recommendation adoption process. Dubbed the “birthplace of genetics,” the Czech city of Brno is the site where Gregor Johann Mendel conducted his famous experiments in plant hybridisation. After joining the Augustinian abbey in Old Brno, then part of the Austrian Habsburg Monarchy, Mendel undertook his studies of the inheritance of certain traits in pea plants in the abbey gardens, and ten years later published the lectures that would firmly establish him as the father of genetics. Mendel was buried in Brno upon his death in 1884. Of course, not all rare diseases are genetic in origin. Other rare conditions, such as the auto-immune disorders, rare infectious diseases, and the majority of rare cancers, have different causes, although for many of these, genes of susceptibility are also being identified. However, the overwhelming majority of rare diseases do have a genetic component and much of what we know of them has grown out of the work pioneered by Gregor Mendel in Old Brno over one hundred years ago. In keeping with this tradition of leading in the field of genetics, the Czech Society of Human Genetics is among the oldest of its kind in the world. Learn more about the history of genetics in the Czech Republic

    The Czech Republic is one of several countries in the European Union that has been forging ahead with a rare disease plan in anticipation of the adoption of the Council Recommendation. Discussions for developing a national plan for the country of some 10 million inhabitants have been underway at the Ministry of Health since early 2009. The Czech National Strategy for Rare Diseases (2009-2019) will build upon existing initiatives in the country as well as establishing new components. Based upon the French and Bulgarian national plans, the Czech strategy will also take into account recommendations received from Orphanet, Eurordis, and the Europlan project.

    The Czech Republic has a number of rare disease resources and activities in place that correspond to the elements specified in the Council Recommendation. There are specialised centers for rare diseases, two of which are the national centre for the diagnosis and treatment of Gaucher disease and another for cystic fibrosis. The value of these hubs has been acknowledged by many of the country’s major stakeholders – including the State Institute for Drug Control, the Czech general insurance company, the Ministry of Health, patient groups, researchers and physicians. The organisation of additional specialised centers will be a part of the Czech strategy.

    In terms of diagnostic services, there are over 40 molecular laboratories in the country. Together, they offer diagnostic tests for more than 300 different rare disorders. Genetic counselling exists for all families at risk. Neonatal screening is routinely performed in the country for PKU, congenital adrenal hyperplasia (CAH) and congenital hypothyroidism. Pilot studies have been conducted for 13 other metabolic disorders (2005) and cystic fibrosis (2006) and these tests will be adopted nationally by the end of 2009. It is commendable that there are clinical genetics services throughout the entire country, with every major district having such services, both at private and/or state based levels. Finally, it is important to note that genetic services are carried out in compliance with all international professional standards and are fully covered by the national health insurance system View the list of molecular laboratories in the Czech Republic

    Rare disease medical coverage in the Czech Republic
    The Czech Republic extends social health coverage to all permanent residents. There are 51 registered orphan medicines of which 28 are currently distributed on a centre basis and are completely reimbursed. The country has therapeutic programmes that allow for the use of certain non-authorised medicinal products. In 2008 a cap to the co-payment by patients of 5000 CZK (€187) per year was established for prescription medicines. Patient participation in expenses for outpatient healthcare facilities was capped at 30 CZK (€1.12) per visit and 60 CZK (€2.24) per day for hospital stays.

    SUKL, the State Institute for Drug Control, is the regulatory body in the Czech Republic responsible for the regulation and surveillance of human medicinal products and medical devices. According to a 2005 survey by the European Medicines Agency entitled, Inventory of Community and Member States’ incentive measures to aid the research, marketing, development and availability of orphan medicinal products, the Czech Republic has a number of mechanisms in place to encourage orphan drug development. For example, “administrative fees are not charged for applications for the registration of medicinal products or for an amendment, extension or transfer of registration of a medicinal product or for authorisations for parallel import of a medicinal product, if the application concerns a medicinal product included in the register of orphan medicinal products under Regulation (EC) No 141/2000 of the European Parliament and of the Council of 16 December 1999 on orphan medicinal products.

    Furthermore, the State Institute for Drug Control “may refrain from recovering costs where these concern operations which are in the public interest or may have especially important implications for the wider population. These operations include applications for: authorisation/registration of clinical assessments of medicinal products and notification to the submitter of additions to the records in cases concerning the evaluation of an orphan medicinal product, and consultation and opinions on such applications; application for registration of an orphan medicinal product and application for amendment, extension or transfer of registration or application for authorisations for parallel import of an orphan medicinal product and consultation and opinions on applications concerning orphan medicinal products”.

    Finally, “… the State Institute for Drug Control may, in the case of orphan medicinal products in justified cases meeting the conditions laid down by decree, allow the registration of a medicinal product or the placing on the market of individual batches of a medicinal product even where the data are indicated on the packaging in a language other than Czech”.

    Information and research
    There are over 40 patient organisations in the Czech Republic, such as the META (for storage diseases); APLA (for autism); the Society for Mucopolysaccharidose Diseases; the Czech CF Association; the Czech Society of Haemophilia; the Czech Union of the Deaf; and the Czech Prader-Willi association. Some groups benefit from aid from the Ministries of Health and of Labour and Social Affairs but the system will be streamlined under the Czech strategy. A few patient organisations also offer recreational services, such as summer camps for children or rehabilitation/therapeutic weekends for adult patients. The Act on Social Services for people with Disabilities came into force in 2007, improving the access to social services for rare disease patients. The patient organisation web sites are one of the few national sources of information for rare diseases. Creating an alliance for rare disease patient groups is a provision of the national strategy being developed.

    Milan Macek in 2006 edited a book of rare disorder case reports intended for Czech pediatricians. This is one of many ways that experts in the country are trying to raise professional awareness for rare diseases and the resources available to diagnose and treat them. Dr. Macek is also an active partner in Orphanet and the EC Rare Diseases Task Force, two other tools that are critical in faciliating the sharing and improving of professional knowledge.

    In terms of research, there are currently 15 different research projects registered with Orphanet, focusing on 30 different rare disorders. At least three projects are targeting specific genes. The Czech Republic also participates in many international-level activities including partnership and/or participation with Orphanet; EuroGentest; Ecorn-CF, a pilot e-health patient/professional project for cystic fibrosis; EuroCareCF, a model project for the complex study of cystic fibrosis; ERNDIM, a consortium for quality assessment in biochemical genetics for rare diseases; RAPSODY , mapping centres of reference for rare diseases in the Czech Republic; and EUROPLAN, developing guidelines for national rare disease plans. The Czech Republic is also a partner country of the Severe Chronic Neutropenia International Registry (SCNIR), monitoring the clinical course, treatment, and disease outcomes in patients with severe chronic neutropenia.

    Rare disease activities under the Czech EU presidency
    As was the case with France, the role of EU presidency has served to boost the country’s level of activity in the field of rare diseases. Under the term of the Czech EU Presidency that ran from January through June of this year, several conferences and workshops were held. There was a European-level workshop in newborn screening and a Forum of National Ethics Councils. An international conference took place in Prague to address the treatment of rare diseases in relation to EU legislation. This event, held in May at the Chamber of Deputies of the Parliament of the Czech Republic under the auspices of Dr. Jozef Kochan, Vice-chairman of the Health Section of the Czech Parliament, was devoted to a discussion of the objectives of the EU in the area of diagnosis and treatment of rare diseases and to the respective tasks ascribed to the individual EU member states in the EU Council Recommendation on European Action adopted under the Czech presidency at the meeting of EU27 Ministers of Health in Luxembourg on 9 June.

    Participants at the conference reviewed the ongoing preparations of the Czech National Strategy for Rare Diseases and discussed access to orphan drugs in the country as well as the role of patient organisations in improving access to such advanced treatments.

    The Czech National Strategy is under negotiation with the Ministry of Health, having developed a working party of expertise to define each element of the plan. A budget is currently being determined for the plan which will get underway in 2010. As is the case with many EU countries, the Czech Republic has its own distinct language. However, there is a proximity to the Slovakian language that may allow the two countries to share resources within the context of the plan. The Czech plan will be unveiled later this year.
    Contact Prof. Milan Macek Jr.


    EU Policy News
    A changing of the guard at the COMP
    The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) recently saw the end of the third mandate for several members. Prof. Magdalena Kuzelova (appointed member from Slovakia), Dr Greg Markey (appointed member from the United Kingdom) Dr Domenica Tarucio (appointed member from Italy) and Mr Yann Le Cam (appointed representative from a Patient Organisation) left the COMP having been warmly thanked for their successful contribution to the work of the Committee. In a press release, the departure of Mr Yann Le Cam was noted as a “milestone in the history of the Committee”. His appointment in 2000 marked the first time patient representatives were represented as full members in an EMEA Scientific Committee and led to several advancements, including the release of the public summary of opinions for orphan designations. The COMP welcomed Dr Tatiana Foltanova (appointed member from Slovak Republic) and Prof. Maurizio Clementi (appointed member from Italy). The Committee also welcomed Ms. Mirjam Söderholm, who will be working with COMP EMEA activities together with Ms Claire Scharf-Kröner at the European Commission, DG Enterprise, Pharmaceuticals. Finally, a decision was taken to postpone the election of the Chair and the Vice-chair to the COMP meeting following the nomination of the four members to the COMP by the EC.

    National & International Policy Developments
    New position paper emphasises the value of storing newborn screening blood spot filter cards for future use
    In late April, the American College of Medical Genetics (ACMG) issued a Position Statement on the Importance of Residual Newborn Screening Dried Blood Spots in response to a call to destroy the filter cards that are used in newborn screening once the initial screening process is terminated. In May 2006, it was recommended that all newborns in the United States be uniformly screened for 29 conditions, most of which are rare and have improved morbidity and mortality when early detection is achieved. To date, many states have followed this recommendation and implemented comprehensive newborn screening practices. A recent report found that at the end of 2008, all 50 states and the District of Columbia had regulation requiring newborn screening for at least 21 disorders. Some 4.2 million US newborns are screened annually in a process that utilises a dried blood spot filter card. The dried blood spots samples from this process can be used again both for follow-up testing and also toward developing improvements in existing newborn screening tests and for the development of new screening tests. Indeed, the dried blood spot is the “only source of material available” for pilot studies necessary before a new test can be introduced. However, a “very small but very vocal minority” is lobbying for the destruction of the residual newborn screening dried blood spot filter cards once the initial newborn screening process has been achieved. The principal concern of this group involves the issue of privacy.

    In response to this concern, the ACMG asserts in its position paper that:

  • Residual newborn screening dried blood filter spots are a valuable national resource that can contribute significantly to the health of our children.
  • Newborn screening blood spots are stored with rigorous control and respect for privacy and confidentiality to protect the public.
  • If a state decides that newborn screening blood spots should not be retained or used for anything more than the screening test, it is critical that individuals have the option of having their children’s dried blood spots deposited in a national repository which will allow for necessary studies under appropriate privacy and confidentiality protections.
  • Consult the ACMG Position paper

    French experts issue clinical recommendations for managing Turner syndrome during pregnancy
    Turner syndrome is a chromosomal disorder associated with the complete or partial absence of an X chromosome. Prevalence is 1 in 2500 girls. The disease is characterised by short stature and ovarian failure. Other manifestations may include bone anomalies, lymphoedema, deafness, and cardiovascular, thyroid and gastrointestinal involvement. Following death from acute aortic dissection of two patients with Turner syndrome who were pregnant via ovocyte donation, the French National College of Gynecologists and Obstetricians and the Biomedicine Agency have developed a set of recommendations for increasing the safety of clinical practices for women with Turner syndrome who wish to become pregnant.
    Consult the recommendations (in French language)

    Other European news
    TREAT-NMD introduces newsletter for Central and Eastern Europe
    Network of excellence for neuromuscular diseases TREAT‐NMD has introduced a newsletter for patient organisations in Central and Eastern Europe. The newsletter provides information on relevant activities, meetings, publications and guidelines. View the newsletter

    Orphanet News
    Orphanet co-publications in practical genetics score high in citations
    Orphanet co-publishes with the European Journal of Human Genetics a series of review articles focussing on the management of genetic diseases. In 2008, seven such "Practical Genetics" articles were published and have received a 3.9 citation score (0-10) - a very satisfactory result for this new Orphanet product.
    New Texts
    Axenfeld–Rieger syndrome and spectrum of PITX2 and FOXC1 mutations in association with the European Journal of Human Genetics

    New Syndromes
    EAST syndrome: epilepsy, ataxia, sensorineural deafness, tubulopathy with KCNJ10 mutations
    The authors report on five children from two consanguineous families presenting with what they are calling EAST syndrome (Epilepsy beginning in infancy, severe Ataxia, moderate Sensorineural deafness, and a renal salt-losing Tubulopathy with normotensive hypokalemic metabolic alkalosis). They found mutations in the gene KCNJ10, which encodes a potassium channel expressed in the brain, inner ear, and kidney. These findings indicate that KCNJ10 plays a major role in renal salt handling and, hence, possibly also in blood-pressure maintenance and its regulation.
    Read the PubMed abstract

    N Engl J Med ; 1960-1970 ; 7 May 2009
    A new syndrome of immunodeficiency and autoimmunity associated with a STIM1 mutation
    The authors report on three siblings from one kindred with a clinical syndrome of immunodeficiency, hepatosplenomegaly, autoimmune hemolytic anemia, thrombocytopenia, muscular hypotonia, and defective enamel dentition. Two of these patients have a homozygous nonsense mutation in STIM1 that abrogates expression of STIM1 and Ca(2+) influx.
    Read the PubMed abstract

    N Engl J Med ; 1971-1980 ; 7 May 2009
    A new syndrome of hereditary leukonychia totalis, acanthosis-nigricans-like lesions and hair dysplasia
    Leukonychia is an ungueal discoloration or dyschromia. The hereditary form is rare. The authors report an original observation of hereditary leukonychia totalis in a father and two of his children, associated with acanthosis-nigricans-like lesions and hair dysplasia. These symptoms were also present in eight other members of the same family.
    Read the PubMed abstract

    Eur J Med Genet ; Epub ahead of print ; 4 May 2009
    Familial idiopathic pulmonary fibrosis, bone marrow hypoplasia and hepatic nodular regenerative hyperplasia
    This is the first report of familial idiopathic pulmonary fibrosis associated with hepatic nodular regenerative hyperplasia and bone marrow hypoplasia presenting in four members of one family. The response to immunosuppressive treatment was poor and all four members succumbed to the disease processes. The current literature is reviewed and mechanisms that could have been involved in the development of this new syndrome are proposed.
    Read the PubMed abstract

    Thorax ; 440-443 ; May 2009
    Microdeletion 15q11.2: a new syndrome in the Prader-Willi/Angelman critical region described in nine patients
    Behavioural differences have been described in patients with type I deletions (between breakpoints 1 and 3 (BP1-BP3)) or type II deletions (between breakpoints 2 and 3) of the 15q11.2 Prader-Willi/Angelman region. The larger type I deletions appear to coincide with more severe behavioural problems (autism, ADHD, obsessive-compulsive disorder). The authors describe nine patients with a microdeletion at 15q11.2 between BP1-BP2 without Prader-Willi/Angelman syndrome who present with several shared clinical features, including delayed motor and speech development, dysmorphisms and behavioural problems (ADHD, autism, obsessive-compulsive behaviour).
    Read the PubMed abstract

    Eur J Med Genet ; 108-115 ; March-June 2009
    Myopathy with cataract and combined respiratory-chain deficiency: nuclear gene GFER is responsible
    Three children born to healthy consanguineous parents presented with progressive myopathy and partial combined respiratory-chain deficiency, congenital cataract, sensorineural hearing loss, and developmental delay. The authors identified a homozygous mutation in nuclear gene GFER encoding a protein localised in the mitochondrial intermembrane space.
    Read the PubMed abstract

    Am J Hum Genet ; 594-604 ; May 2009

    New Genes

    Frontonasal dysplasia: recessive mutations in the ALX3 homeobox gene at cause
    The authors describe a recessively inherited frontonasal malformation characterised by a distinctive facial appearance, with hypertelorism, wide nasal bridge, short nasal ridge, bifid nasal tip, broad columella, widely separated slit-like nares, long philtrum with prominent bilateral swellings, and midline notch in the upper lip and alveolus. Additional recurrent features present in a minority of individuals have been upper eyelid ptosis and midline dermoid cysts of craniofacial structures. The authors identified mutations in ALX3, encoding the aristaless-related ALX homeobox 3 transcription factor and conclude that ALX3 is essential for normal facial development in humans and that deficiency causes a clinically recognisable phenotype.
    Read the PubMed abstract

    To read more about "Frontonasal dysplasia"

    Am J Hum Genet ; 698-705 ; May 2009
    Nonsyndromic progressive hearing loss: a micro-RNA is mutated
    The authors demonstrate that point mutations in the seed region of miR-96, a miRNA expressed in hair cells of the inner ear, result in autosomal dominant, progressive hearing loss. This is the first study implicating a miRNA in a mendelian disorder. The identified mutations have a strong impact on miR-96 biogenesis and result in a significant reduction of mRNA targeting. In a second article, the authors, in collaboration with other researchers, describe potential targets of miR-96 identified in the mouse.
    Read the first PubMed abstract
    Read the second PubMed abstract

    To read more about "Nonsyndromic genetic deafness"

    Nat Genet ; 609-613 ; May 2009
    Nat Genet ; 614-618 ; May 2009

    Pulmonary arterial hypertension: a nonsense mutation of SMAD8 is associated
    The authors describe the first mutation in the gene SMAD8 in a patient with idiopathic pulmonary arterial hypertension. This gene is the third belonging to the transforming growth factor (TGF)-beta superfamily to be linked to the disease.
    Read the PubMed abstract

    To read more about "Pulmonary arterial hypertension"

    J Med Genet ; 331-337 ; May 2009
    Fetal akinesia sequence: a germline mutation in DOK7 is associated
    Fetal akinesia sequence syndrome (FAS) is a heterogeneous disorder characterised by fetal akinesia and developmental defects including, in some case, pterygia. Multiple pterygium syndromes (MPS) are traditionally divided into prenatally lethal and non-lethal (such as Escobar) types. A homozygous DOK7 splice site mutation was identified in a family with three children affected with lethal FAS. Partial DOK7 mutations have been reported to underlie congenital myasthenic syndrome.
    Read the PubMed abstract

    To read more about "Fetal akinesia sequence"

    J Med Genet ; 338-340 ; May 2009
    Nijmegen breakage syndrome: RAD50 deficiency identified
    The authors report on a patient previously diagnosed as probably having Nijmegen breakage syndrome, with microcephaly, intellectual deficit, "bird-like" face, and short stature. At variance with this diagnosis, she never had severe infections, had normal immunoglobulin levels, and did not develop lymphoid malignancy up to age 23 years. The authors found that she is compound heterozygous for mutations in the RAD50 gene that give rise to low levels of unstable RAD50 protein.
    Read the PubMed abstract

    To read more about "Nijmegen breakage syndrome"

    Am J Hum Genet ; 605-616 ; May 2009
    Nonsyndromic hearing loss: KCNJ10 and SLC26A4 mutations digenic form associated with enlarged vestibular aqueduct syndrome
    Mutations in the SLC26A4 cause nonsyndromic hearing loss associated with an enlarged vestibular aqueduct (known as DFNB4) and Pendred syndrome (PS), the most common type of autosomal-recessive syndromic deafness. In many patients with a DFNB4/PS phenotype, mutation screening of SLC26A4 fails to identify two disease-causing allele variants. That a sizable fraction of patients carry only one SLC26A4 mutation suggests that DFNB4/PS is a complex disease involving other genetic factors. Here, the authors show that mutations in the inwardly rectifying K(+) channel gene KCNJ10 are associated with nonsyndromic hearing loss in carriers of SLC26A4 mutations with an DFNB4/PS phenotype. In probands from two families, they identified double heterozygosity in affected individuals. These persons carried single mutations in both SLC26A4 and KCNJ10. The KCNJ10 mutations reduce K(+) conductance activity, which is critical for generating and maintaining the endocochlear potential.
    Read the PubMed abstract

    To read more about "Nonsyndromic genetic deafness"

    Am J Hum Genet ; 651-657 ; May 2009
    Sex inversion: mutations in the CBX2 gene found in a girl with a 46,XY karyotype
    A girl with a prenatal 46,XY karyotype was born with a completely normal female phenotype, including uterus and histologically normal ovaries. In mice with a similar phenotype, the ablation of M33, an ortholog of Drosophila Polycomb, causes male-to-female sex reversal. The analysis of the human homolog of M33, Chromobox homolog 2 (CBX2), in this girl revealed loss-of-function mutations.
    Read the PubMed abstract

    Am J Hum Genet ; 658-663 ; May 2009
    Congenital glaucoma: null mutations in LTBP2 at cause
    Primary congenital glaucoma (PCG) is an autosomal-recessive condition characterised by high intraocular pressure (IOP), usually within the first year of life, which potentially could lead to optic nerve damage, globe enlargement, and permanent loss of vision. The authors report that null mutations in the LTBP2 gene cause PCG in four consanguineous families from Pakistan and in patients of Gypsy ethnicity. LTBP2 is the largest member of the latent transforming growth factor (TGF)-beta binding protein family, which are extracellular matrix proteins with multidomain structure.
    Read the PubMed abstract

    To read more about "Glaucoma, congenital"

    Am J Hum Genet ; 664-671 ; May 2009
    Moyamoya disease: mutations in smooth muscle alpha-actin (ACTA2) at cause
    The vascular smooth muscle cell (SMC)-specific isoform of alpha-actin (ACTA2) is a major component of the contractile apparatus in SMCs located throughout the arterial system. Heterozygous ACTA2 mutations cause familial thoracic aortic aneurysms and dissections, but only half of mutation carriers have aortic disease. Linkage analysis and association studies of individuals in 20 families with ACTA2 mutations indicate that mutation carriers can have a diversity of vascular diseases, including premature onset of coronary artery disease and premature ischemic strokes, including Moyamoya disease.
    Read the PubMed abstract

    To read more about "Moyamoya disease"

    Am J Hum Genet ; 617-627 ; May 2009
    Infantile hypertrophic cardiomyopathy: a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes at cause
    Infantile cardiomyopathy is a genetically heterogeneous disorder with significant morbidity and mortality. This study identified in four unrelated patients who presented as infants with isolated hypertrophic cardiomyopathy a novel mitochondrial mutation affecting two mitochondrial genome-encoded complex V subunit proteins.
    Read the PubMed abstract

    To read more about "Cardiomyopathy, hypertrophic, primary or idiopathic"

    J Med Genet ; 308-314 ; May 2009
    Frontemporal dementia: TARDBP mutations identified
    TDP-43 (TAR-DNA binding protein) aggregates in neuronal inclusions in motoneuron disease (MND), as well as in frontemporal dementia (FD) and FD associated with MND (FD-MND). Mutations in the TARDBP gene, coding for TDP-43, have been identified in MND patients. The authors now describe TARDBP mutations in two patients with FD-MND, presenting with a behavioural variant of FD and semantic dementia, suggesting that TDP-43 may also have a direct pathogenic role in FD disorders.
    Read the PubMed abstract

    To read more about "Frontotemporal dementia"

    Ann Neurol ; 470-473 ; April 2009

    Research in Action

    Fundamental Research
    Mucopolysaccharidosis type III B is also a tauopathy
    Mucopolysaccharidosis type III B (MPSIII B) is an autosomal recessive, neurodegenerative disease of children, characterised by profound cognitive deficit and dementia. The primary cause is mutation in the NAGLU gene, resulting in deficiency of alpha-N-acetylglucosaminidase and lysosomal accumulation of heparan sulfate. In the mouse model of MPSIII B, neurons and microglia display the characteristic vacuolation of lysosomal storage of undegraded substrate, but neurons in the medial entorhinal cortex (MEC) display accumulation of several additional substances. In this study, the authors discovered hyperphosphorylated tau (P-tau) in MEC of Naglu(-/-) mice, in the same neurons as lysozyme. In older mutant mice, it was also seen in the dentate gyrus, an area important for memory. Electron microscopy of dentate gyrus neurons showed cytoplasmic inclusions of paired helical filaments, P-tau aggregates characteristic of tauopathies-a group of age-related dementias that include Alzheimer disease. These findings indicate that mucopolysaccharidosis type III B should also be considered a tauopathy.
    Read the PubMed abstract

    To read more about "Mucopolysaccharidosis type 3"

    Proc Natl Acad Sci USA ; 8332-8337 ; 19 May 2009
    Neurofibromatosis type 1: mechanisms in the pathogenesis of malignant tumours
    Neurofibromatosis type 1 (NF1) is a familial tumour syndrome. Malignant tumours can arise in the nervous and non-nervous system in either childhood or adulthood, with malignant peripheral nerve sheath tumours being most common. Several pathways are thought to be involved in the development of tumours associated with NF1: rat sarcoma viral oncogene homologue (RAS)-mitogen activated protein kinase (MAPK), mammalian target of rapamycin, and P21 protein (Cdc42/Rac)-activated kinase 1. New insights into the pathogenesis of these tumours will lead to a better understanding of tumour origin and development and will hopefully allow the discovery of new and specific treatments.
    Read the PubMed abstract

    To read more about "Neurofibromatosis type 1"

    Lancet Oncol ; 508-515 ; May 2009
    Clinical Research
    Mucosal Schwann cell hamartoma: a new entity?
    Schwannoma is a well-described, benign nerve sheath tumour of the soft tissue, but is rare in the gastrointestinal tract. Gastrointestinal schwannomas are often incidentally discovered as small polypoid intraluminal lesions. In this report, the authors describe the clinicopathologic and immunohistochemical features of a distinctive neural mucosal polyp composed of a diffuse cellular proliferation of uniform bland spindled cells in the lamina propria that entraps the colonic crypts. To avoid confusion of these solitary colorectal polyps containing pure spindled Schwann cell proliferation in the lamina propria with neural lesions that have significant association with inherited syndromes, the authors recommend the designation "mucosal Schwann hamartoma".
    Read the PubMed abstract

    World J Gastroenterol ; 2287-2289 ; 14 May 2009
    22q11.2 deletion syndrome: premature death in adults
    22q11.2 deletion syndrome (22q11.2DS) is a multisystem disease with a prevalence of 1/4000. Variable expression of congenital and later onset features contributes to its under-recognition. Longevity in those surviving childhood is believed to be normal but data are limited. The authors prospectively followed 102 adults with 22q11.2DS and their 162 unaffected siblings. They found that individuals with 22q11.2DS who survive childhood have diminished life expectancy and increased risk of sudden death not attributable to any single factor. Some sudden and/or premature deaths observed in the general population may represent undiagnosed 22q11.2DS.
    Read the PubMed abstract

    To read more about "Monosomy 22q11"

    J Med Genet ; 324-330 ; May 2009
    Microduplication 22q11.2: a clinical description based on 50 cases
    The authors present a clinical description of 22q11.2 duplication. The phenotype of patients is extremely variable, ranging from multiple defects to mild learning difficulties, heart defects, urogenital abnormalities, velopharyngeal insufficiency with or without cleft palate, and with some individuals being essentially normal. The basis of phenotype variability remains to be elucidated. The large majority of affected individuals have identical 3Mb duplications. Diagnostic and pathogenetic aspects of the disease are also discussed.
    Read the PubMed abstract

    To read more about "Trisomy 22q11"

    Eur J Med Genet ; 88-93 ; March-June 2009
    Wegener granulomatosis: severe impaired respiratory ciliary function
    The pathogenesis of granulomatous inflammation in the respiratory tract and autoimmunity in Wegener granulomatosis (WG) are poorly understood. The authors investigated ciliary beat frequency (CBF) in WG. Nasal epithelial cells were obtained from 30 patients with WG with involvement of the upper respiratory tract, 12 patients with other inflammatory rheumatic disease and 10 healthy controls. They found that CBF is severely impaired in WG, potentially influenced by immunosuppressive treatment.
    Read the PubMed abstract

    To read more about "Wegener granulomatosis"

    Ann Rheum Dis ; 1067-1071 ; June 2009
    Therapeutic Approaches
    Mendelian susceptibility to atypical mycobacteria: antisense-mediated exon skipping corrects IL-12Rbeta1 deficiency in T cells
    Patients with Mendelian susceptibility to mycobacterial disease have severe, recurrent life-threatening infections with otherwise poorly pathogenic mycobacteria and salmonellae. The extreme susceptibility is the result of genetic defects in the interleukin-12/interferon-gamma (IL-12/IFN-gamma) pathway. The authors showed that T cells can be highly efficiently transduced with antisense oligonucleotides and are amenable to antisense-mediated exon skipping. Furthermore, they demonstrate that exon skipping (partly) corrects the IL-12Rbeta1 deficiency in patients’ cells.
    Read the PubMed abstract

    To read more about "Mendelian susceptibility to atypical mycobacteria"

    Blood ; 4548-4555 ; 7 May 2009
    Pseudoxanthoma elasticum: elevated dietary magnesium prevents connective tissue mineralisation in a mouse model
    Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder characterised by ectopic connective tissue mineralisation, with clinical manifestations primarily in the skin, eyes, and cardiovascular system. There is considerable, both intra- and interfamilial, variability in the spectrum of phenotypic presentation. Previous studies have suggested that mineral content of the diet may modify the severity of the clinical phenotype. In this study, the authors utilised a targeted mutant mouse to examine the effects of changes in dietary phosphate and magnesium on the mineralisation process using calcification of the connective tissue capsule surrounding the vibrissae as an early phenotypic biomarker. Mice placed on diet enriched in magnesium (fivefold) showed no evidence of connective tissue mineralisation. The inhibitory capacity of magnesium was confirmed in a cell-based mineralization assay system in vitro.
    Read the PubMed abstract

    To read more about "Pseudoxanthoma elasticum"

    J Invest Dermatol ; 1388-1394 ; June 2009

    Patient Management and Therapy

    Glioblastoma: five-year survival better with concomitant temozolomide versus radiotherapy alone
    In 2004, a randomised phase III trial by the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group reported improved median and 2-year survival for patients with glioblastoma treated with concomitant and adjuvant temozolomide and radiotherapy. The authors report the final results with a median follow-up of more than 5 years. Of the 573 patients assigned to treatment, 97% in the radiotherapy alone group and 89% in the combined-treatment group died during the 5 year follow-up period. A benefit of combined therapy was recorded in all clinical prognostic subgroups, including patients aged 60-70 years.
    Read the PubMed abstract

    To read more about "Glioblastoma"

    Lancet Oncol ; 459-466 ; May 2009
    Charcot-Marie-Tooth disease type 1A: ascorbic acid in children is safe but efficacy endpoints are not attained
    Charcot-Marie-Tooth disease type 1A (CMT1A) is characterised by peripheral nerve demyelination, weakness, and impaired motor function and is caused by the duplication of PMP22, the gene that encodes peripheral myelin protein 22. High-dose ascorbic acid has been shown to have remyelinating potential and to correct the phenotype of a transgenic mouse model of CMT1A by decreasing expression of PMP22. The authors tested the efficacy and safety of ascorbic acid supplementation in 81 children with CMT1A in a randomised, double-blind, placebo-controlled trial. The ascorbic acid group had a small, non-significant increase in median nerve motor conduction velocity compared with the placebo group but there was no measurable effect of ascorbic acid on neurophysiological, strength, function, or quality of life outcomes. While 12 months of treatment with high-dose ascorbic acid was safe and well tolerated, none of the expected efficacy endpoints were reached.
    Read the PubMed abstract

    To read more about "Charcot-Marie-Tooth disease, type 1A"

    Lancet Neurol ; 537-544 ; June 2009

    Orphan Drugs
    Fourteen positive opinions for orphan designation at the June COMP meeting
    At the June 2009 meeting of the Committee for Orphan Medicinal Products (COMP), fourteen positive opinions were issued for the treatment of:
    - cystic fibrosis (two products)
    - chronic iron overload requiring chelation therapy
    - acute promyelocytic leukaemia
    - solar urticaria
    - Hodgkin lymphoma
    - acute lymphoblastic leukaemia
    - atopic keratoconjunctivitis
    - haemolytic uremic syndrome
    - haemophilia A
    - diffuse large B-cell lymphoma
    - mucopolysaccharidosis, type IVA (Morquio A Syndrome)
    - acute myeloid leukaemia
    - pancreatic cancer

    Consult the European Register of Designated Orphan Medicinal Products
    Consult the Orphanet list of orphan drugs authorised for marketing in Europe


    National Center for Canine Models of Duchenne Muscular Dystrophy Call for Proposals
    The National Center for Canine Models of Duchenne Muscular Dystrophy (NCDMD) at the University of North Carolina at Chapel Hill (USA) is encouraging submission of subsidy applications covering all treatment modalities from a variety of investigators with diverse academic and corporate backgrounds. Deadline: 15 July 2009. For further details

    Partnersearch, Job Opportunities
    Bio-Health Informatics Scientist
    Based in the National Genetics Reference Laboratory in Manchester (UK), the position involves the identification and encoding of rare, mostly genetic, diseases for representation in the Orphanet encyclopaedia and participation in the revision of the International Classification of Diseases version 10 (ICD-10), cross-referencing the diseases to the standard coding systems SNOMED-CT, MeSH and MedDRA. A good first degree in a computer science or health informatics discipline, or in a relevant biological discipline or equivalent, with demonstrated abilities in health informatics is required, along with knowledge of a bio-health based discipline and skills in ontology development and use, programming and/or scripting, preferably in Java, and experience of ICD-10, SNOMED-CT, MeSH and MedDRA. For further details

    News from the Patients' Associations
    Eurordis 2008 activity report reflects advances made for rare disease patients on many fronts
    The European Organisation for Rare Diseases (Eurordis), a pan-European alliance for patient groups, has issued its annual report of activity for 2008. The role of the patient in rare disease policy, public awareness, research, and treatment, is proving more and more critical and Eurordis has a pivotal role in many actions. In particular, EURORDIS contributed significantly to the momentum that pushed the Council Recommendation for a European Action in the Field of Rare Diseases across the finish line earlier this month when the EU Council, under the auspices of the Czech Republic EU presidency, gave its final approval to adopt the important document. Eurordis also initiated the first Day for Rare Diseases, a European event that quickly caught fire around the world and is proving highly effective in raising public awareness for the complex issues surrounding rare diseases. The present Eurordis strategic approach involves keeping rare diseases a priority on the European agenda; building a broader grassroots patient-centred community; and encouraging budget growth and funding diversification. The ever-expanding Eurordis has 360 member organisations in 39 countries, including 19 national alliances. More than 600 individual rare disease patient groups in Europe are represented encompassing over 1000 rare diseases. The annual report provides a recap of the many initiatives and activities in which the alliance is involved. Consult the Eurordis 2008 activity report
    The National Organization for Rare Disorders presents annual awards
    In a gala event that took place in May, the National Organization for Rare Disorders (NORD) acknowledged the achievements of individuals and organisations toward improving conditions for rare disease patients and their families. NORD, the alliance for rare disease patients in the USA, holds the awards event each year. Amongst the honourees recognised this year were Senator Edward Kennedy, Social Security Commissioner Michael J. Astrue, who worked to reduce the disability backlog, and Director of the National Institutes of Health Clinical Center John I. Gallin, MD. The Discovery Health television channel was recognised for its educational programming in the field. Amongst the members of industry awarded were Bayer HealthCare Pharmaceuticals, Onyx Pharmaceuticals, Baxter International, BioMarin Pharmaceutical, Biovail Corporation, CSL Behring, Eisai, GTC Biotherapeutics, Regeneron Pharmaceuticals, Talecris Biotherapeutics, and ViroPharma – all of whom contributed to developing treatments for rare conditions, including hepatocellular carcinoma, severe congenital protein C deficiency, phenylketonuria, chorea associated with Huntington disease, acute bleeding episodes in patients with congenital fibrinogen deficiency, Lennox-Gastaut syndrome, hereditary antithrombin deficiency, autoinflammatory disorders known as CAPS, chronic inflammatory demyelinating polyneuropathy, and hereditary angioedema. Finally, a new honour – the Abbey S. Meyers Leadership Award, established in honour of the founding president of NORD – was presented to the Huntington’s Disease Society of America, and a posthumous honour went to Patty Delaney, an FDA staff member who was a strong advocate for patients. In a press release, NORD President and CEO Peter L. Saltonstall observed of the honourees that they “…demonstrated compassion and concern for what was once a forgotten community—people who have diseases affecting small patient populations. We are happy to honor them for accomplishments that have literally saved lives."

    What's on Where?
    Balkan Congress for Rare Diseases
    Date: 26-27 June 2009
    Venue: Cluj-Napoca, Romania

    This conference will address issues in diagnosing and managing rare diseases in the region and will explore ways to increase European collaboration.
    For further details

    2nd ELA Research Foundation Congress
    Date: 26-27 June 2009
    Venue: Luxembourg

    “Therapeutic challenge in white matter diseases” is the theme of this congress that will bring together leading international experts in leukodystrophies, myelin biology, neuroimaging, stem cell research and gene therapy to share and discuss recent advances and cutting-edge science in these fields with the ultimate goal to fight and eventually find a cure for the disabling leukodystrophies and myelin diseases.
    For further details

    Seventh International Progressive Supranuclear Palsy Medical Workshop
    Date: 7 July 2009
    Venue: London, UK

    This year’s event is entitled “The Progressive Supranuclear Palsy Jigsaw – Corners and Edges”. Topics include aetiology, diagnosis, treatment, and palliation.
    For further details

    Crafting a Plan for Rare Disease Drug Development
    Date: 17 July 2009
    Venue: Maryland, USA

    This workshop will focus on solutions to the specific limiting problems of rare disease drug development, with a deliverable, milestone, and results-oriented approach.
    For further details

    Cornelia de Lange Syndrome World Conference
    Date: 23 July 2009
    Venue: Brighton, UK

    This event is part of the Cornelia de Lange Syndrome World Conference and is aimed at teachers, support staff and health professionals who work with children and adults with intellectual disability, autism spectrum disorder and genetic syndromes. The focus is on identifying and responding to the critical personal and family issues that affect the day to day quality of life of all people with intellectual disability. Cornelia de Lange syndrome will be highlighted.
    For further details

    Treatment Options in Phenylketonuria and Related Pediatric Neurotransmitter Disorders
    Date: 29 August 2009
    Venue: San Diego, California

    Key Topics include challenges in the pharmaceutical treatment of PKU and treatment of paediatric neurotransmitter disorders.
    For further details

    14th International World Muscle Congress
    Date: 9-12 September 2009
    Venue: Geneva, Switzerland

    New methods for assessing disease progression in neuromuscular disorders; The extracellular matrix in normal and diseased muscle (including collagen and glycosylation disorders, fibrosis, patterning and cell grafting); Advances in treatment of neuromuscular disorders. A satellite teaching course will also be held from 8-9 September 2009.
    For further details

    Genetics and Genomics of Vascular Disease Workshop
    Date: 13-16 September 2009
    Venue: Hyannis, MA

    The programme will present cutting edge research in areas like genome wide association studies in human populations, mouse QTL mapping of vascular phenotypes, and pathogenesis of vascular and developmental diseases using human patients and mouse models.
    For further details

    European Working Group on Rett Syndrome – 2009 Meeting
    Date: 17-19 September 2009
    Venue: Stresa, Italy

    An opportunity to discuss Rett syndrome-related science, to find collaborators for grant applications, and to exchange reagents and ideas. Moreover, the close contact with the parents associations should also help to focus better on the scientific problems that need to be resolved to find a cure for patients.
    For further details

    British Paediatric Neurology Association: Rare Disorders Symposium
    Date: 29 September 2009
    Venue: Harrogate, England

    A stand-alone satellite symposium on rare disorders will take place as part of the 8th Paediatric Neurology Conference, exploring a number of themes relating to rare disorders.
    For further details

    Fourth International Conference on Birth Defects and Disabilities in the Developing World
    Date: 4-7 October 2009
    Venue: New Delhi, India

    The theme of the Fourth International Conference is "Translating Research into Cost-effective Services for the Care and Prevention of Birth Defects, Preterm Birth and Consequent Disabilities".
    For further details

    EPPOSI: 10th Workshop on Partnering for Rare Disease Therapy Development
    Date: 26-27 October 2009
    Venue: Brussels, Belgium

    The topic of this year’s workshop of the European Platform for Patients’ Organisations, Science and Industry is “10 years after the adoption of the EU Orphan Medicines Regulation: Where do we go? Three key themes will be addressed: “What is the impact of the economic crisis on the field of rare diseases – and what is the vision on further progress in R&D, diagnosis and patient care? Building on the public policy base of the last 10 years: how to advance policies in the next five years? Rare cancers: specific challenges within rare diseases.
    For further details

    TREAT-NMD/NIH International Conference
    Date: 17-19 Nov 2009
    Venue: Brussels, Belgium

    The aim of the meeting is to share progress in the area of translational medicine in inherited neuromuscular diseases and set the future collaborative agenda. This conference will build on achievements of the NIH and TREAT-NMD. It will be a highly interactive meeting with a strong focus on the key issues surrounding "trial readiness" in the neuromuscular field.
    For further details

    ESF-UB Conference in Biomedicine: Rare Diseases II: Hearing and Sight Loss
    Date: 22-27 November 2009
    Venue: Sant Feliu de Guixols, Spain

    A conference of the European Science Foundation. The meeting will bring together experts in sensory neuroscience, developmental biology, genetics, cell biology, modelling, translational research and therapy. It aims at promoting exchanges between the scientists of the two fields and beyond, at stimulating the emergence of new research projects at the interface between disciplines and at training young researchers in this interdisciplinary field.
    For further details

    18th International Workshop on Vascular Anomalies
    Date: 21-24 April 2010
    Venue: Brussels, Belgium

    The programme for this workshop will be available soon.
    For further details

    5th European Conference on Rare Diseases 2010
    Date: 13-15 May 2010
    Venue: Krakow, Poland

    Details will be available soon.


    Orphanews Europe, the newsletter of the Rare Diseases Task Force
    Orphanews Europe is supported by the European Commission's DG SANCO
    and the French Muscular Dystrophy Association (AFM)
    Editor-in-chief: Ségolène Aymé
    Editor: Louise Taylor
    Contact Us
    Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Charlotte Rodwell, Claire Scharf-Kroener, Paloma Tejada, Aurélie Vandeputte
    National Contact Point: Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
    For more information on the Rare Diseases Task Force
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