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Recommendations for Centres of Expertise adopted unanimously by the European Union Committee of Experts on Rare Diseases

On 24 October, during the third meeting of the European Union Committee of Experts on Rare Diseases (EUCERD), the Recommendations on Quality Criteria for Centres of Expertise for Rare Diseases in Member States were unanimously adopted by the 51-member EUCERD, which has representatives from all 27 EU Member States and from all domains relevant to the fields of rare diseases and orphan drugs, including academia, government, the biopharmaceutical industry and patient organisations. This is the first set of recommendations adopted by this committee. Developing Centres of Expertise and European Reference Networks in the field of rare diseases has been proposed in the Council Recommendation on an Action in the Field of Rare Diseases and more recently in the Cross-Border Healthcare Directive as a means of organising care for the thousands of heterogeneous rare conditions affecting scattered patient populations across Europe. In order to share knowledge and expertise more efficiently, the EUCERD recommendations seek to introduce harmonious standards of quality practices by elaborating criteria for the Member States to incorporate into their process to designate Centres of Expertise.

EUCERD, formally the Rare Diseases Task Force, has already issued a series of reports investigating the state-of-the-art in the field. The 45 Recommendations build upon this work already achieved and assist the Member States to develop their healthcare pathways at both the national and EU levels in the field of rare diseases. The recommendations cover the Mission and Scope of the Centres of Expertise; the Criteria for Designating Centres of Expertise; the Process of Designating and Evaluating National Centres of Expertise; and the European Dimension of Centres of Expertise.

The EUCERD Recommendations on Quality Criteria for Centres of Expertise for Rare Diseases in Member States are available on the EUCERD website.

Spotlight on...
NIMBL ... Investigating the genetic and cellular basis of Nuclease Immune Mediated Brain and Lupus-like conditions

NIMBL is a €5.4 million 3 year EU-funded study, investigating the genetic and cellular basis of Nuclease Immune Mediated Brain and Lupus-like conditions, including:
  • Aicardi-Goutieres syndrome (AGS)
  • Retinal vasculopathy with cerebral leukodystrophy (RVCL)
  • Familial chilblain lupus (FCL)
  • Certain cases of systemic lupus erythematosus (SLE)

  • The study, which started in June 2010, is a collaboration between geneticists, neurologists, and immunologists from the UK, the Netherlands, Italy, Spain and the USA. The project is led by Professor Yanick Crow based in Manchester, who kindly agreed to provide an overview of the project for OrphaNews Europe.

    The aims of the project
    NIMBL conditions are rare. A major purpose of the NIMBL consortium is to share information about these rare disorders, and thus increase knowledge of their natural history, genetic basis, and cellular pathology.

    This should enable:
  • Earlier, faster and more accurate diagnosis in the future
  • The development of new treatments
  • Insight into the causes of other autoimmune / autoinflammatory conditions

  • NIMBL Study Design
    Affected individuals and their relatives are invited to provide clinical information and biological samples. NIMBL scientists will:
  • Investigate the genetic basis of the NIMBL conditions in a large group of patients
  • Study the function of the genes that are involved, and how the gene products are modified in affected individuals
  • Use cell-lines and genetically modified mice to investigate the biology of the AGS-related genes and proteins in health and disease
  • Use cell-lines and genetically modified mice to investigate potential drug targets and test the effectiveness of new treatments

  • Aicardi-Goutieres syndrome
    Aicardi-Goutieres syndrome (AGS) is an early-onset inflammatory disorder particularly affecting the brain and the skin. The disease is frequently associated with severe intellectual and physical handicap. Some infants with AGS show features mimicking those observed when a baby is infected by a virus in the womb. Other children are apparently normal for a period of time after birth, and then develop features in the first few months of life. More recently, non-specific inflammatory phenotypes, in some cases with minimal neurological impairment, have been recognised - particularly in relation to SAMHD1-associated disease.

    Currently there are five genes implicated in AGS: TREX1, RNASEH2A, RNASEH2B, RNASEH2C, and SAMHD1. Testing these genes can confirm a diagnosis of AGS in about 90% of individuals who show typical features of the disease. Usually, AGS is inherited as an autosomal recessive trait. However, rare cases can arise due to new autosomal dominant mutations.

    Familial chilblain lupus
    Familial chilblain lupus (FCL) is a cutaneous form of systemic lupus erythematosus (SLE). Currently, TREX1 and SAMHD1 mutations are known to be associated with FCL, inherited in an autosomal dominant manner.

    Retinal vasculopathy with cerebral leukodystrophy
    Retinal vasculopathy with cerebral leukodystrophy (RVCL) is very rare, with only a few families known world-wide. However, it is likely that the disease is underdiagnosed. The condition most frequently shows itself at around the age of 45 years, with patients developing signs and symptoms involving the central nervous system. Not infrequently, patients are initially misdiagnosed as having a brain tumour or multiple sclerosis. Death can occur within 10 years of the first symptoms appearing. The disease is associated with three-prime terminal heterozygous null mutations in TREX1 (the AGS1 gene).

    Systemic lupus erythematosus
    SLE is a rare (3-25 / 100,000 / year in the UK), multi-system, autoimmune disease characterised by the production of auto-antibodies (most particularly to nucleic acids). Through NIMBL, the researchers are interested in defining single-gene disorders that predispose to the development of SLE as a tractable approach to understanding the pathogenesis of lupus. As proof of principle of this research strategy, the researchers recently showed that biallelic mutations in the ACP5 gene, encoding tartrate resistant acid phosphatase (TRAP), significantly predispose to the development of lupus on a Mendelian basis.

    NIMBL news and events
    The project first year conference was held in Brussels on the 6th June 2011, where the NIMBL partners met to discuss the study and share ideas. A patient conference was held in Washington DC on 30th April 2011, and a video of this will be available on the NIMBL website soon. The NIMBL project leaders are planning a NIMBL family day in 2012, where they hope to collect clinical information and samples from affected patients and their family members, and which will include parent-scientist sessions, and an opportunity for families to meet one another.

    For more information about NIMBL visit the website
    Contact NIMBL
    Contact Carina Donnelly at NIMBL
    Contact Yanick Crow at NIMBL


    EU Policy News

    Clinical Trials Directive again comes under fire from research organisations urging reform
    Sixteen European medical research organisations, including Cancer Research UK, the Academy of Medical Sciences, the British Heart Foundation, the Wellcome Trust and the European Science Foundation have joined forces to plead for reforms to the Clinical Trials Directive (2001/20/EC), asserting that the legislation is hampering research into potentially lifesaving treatments while adding nothing to the patient safety it is supposed to enhance. The Clinical Trials Directive, which delineates the legal requirements for conducting clinical studies in the European Union, has been blamed for increasing the costs and time to launch trials due to burdensome and complex administrative procedures. There is a very real fear that the Directive is driving medical research out of the EU and the petition calls for urgent revision. In a press release, Professor Liselotte Hojgaard, chair of the European Medical Research Councils of the European Science Foundation, remarked: "The current system of regulation for clinical trials is unnecessarily complex and bureaucratic and we believe this is holding back progress in medical research across Europe. It's vital that the recommendations put forward in this statement are taken forward to ensure that Europe continues to be seen as an attractive destination for clinical research".
    Consult 2001/20/EC (the Clinical Trials Directive)

    Mid-Term Evaluation of the EU Health Strategy 2008-2013 final report encompasses rare diseases in its scope
    The final report of the Mid-Term Evaluation of the EU Health Strategy 2008-2013 is available online. Prepared by the Public Health Evaluation and Impact Assessment Consortium, the evaluation was commissioned by DG Sanco in order to guide the implementation of the Strategy going forward, and to take stock of the actions implemented to date. Rare diseases fall within the scope of the EU Health Strategy and the number of Member States (MS) that have adopted an action plan on rare diseases, on the basis of the Council Recommendation of 8 June 2009 on an Action in the Field of Rare Diseases, is listed as a proposed implementation indicator that can serve to measure future progress of MS against the EU Health Strategy. The report cites the issue of the Communication on a European Action in the Field of Rare Diseases as an action that demonstrates progress made in relation to stated EU Health Strategy actions. A table in the report that lists the numbers of EC action areas in relation to the EU Health Strategy does not distinguish rare diseases from chronic, common or communicable disorders and thus is of limited interest to the rare disease community. Globally, the report finds that “In most MS, the influence of the EU Health Strategy on national health strategies is limited”… and that…“The EU Health Strategy’s main value is that it acts as a guiding framework and, to some extent, as a catalyst for actions at the EU level”.
    Consult the Mid-Term Evaluation of the EU Health Strategy 2008-2013

    DG Research
    E-Rare announces projects selected for funding from 2011 Joint Transnational Call in its first newsletter
    E-Rare, the ERA-Net on rare diseases, supported by the European Commission ERA-Net scheme under the Seventh Framework Programme, is a network of sixteen partners – public bodies, ministries and research funding organisations – from twelve countries, responsible for the development and funding of national/regional research programmes on rare diseases. E-Rare has just issued its very first newsletter. Amongst the featured news is the list of projects funded under its third Joint Transnational Call 2011. Funding bodies from nine countries joined this call: Austria, Belgium (Flanders and French speaking community agencies), France, Germany, Greece, Israel, Italy, Spain and Turkey. From a total of 146 pre-proposals, 39 were selected for full submission. Of these, 13 consortia with a foreseen budget of about €9 million were selected for funding. The rare disease areas of the chosen projects include haematology, metabolic diseases, neurology, dermatology, and congenital malformations. Therapeutic approaches include pluripotent stem cells, gene therapy vectors and customised animal models. In other news, E-Rare recently revamped its website, giving it a fresh new look and adding many novel features.
    Consult the first E-Rare newsletter and the results of the Joint Transnational Call 2011

    Database of clinical studies involving children available via the EMA
    Last month, the European Medicines Agency made available a database housing information on clinical studies of medicines authorised in the European Union that involved paediatric populations and were completed prior to the 2007 Paediatric Regulation came into effect. Via the Article 45 Paediatric Studies Database, it is possible to access information including the name and goal of the study, the medicinal product involved, and data on the patients, including age. Some trial outcomes are also available. The database is part of a global aim of the Agency to enhance transparency. The Agency is also specifically focused on improving information on medicinal products for paediatric populations.
    Visit the database


    National & International Policy Developments
    Final report of the Recommendations and Proposed Measures for a Belgian Plan for Rare Diseases submitted to the Health Ministry

    The final report Recommendations and Proposed Measures for a Belgian Plan for Rare Diseases was submitted to the Minister of Social Affairs and Public Health last month. The report is also available online on the website of the King Baudouin Foundation in English, French, German and Dutch languages. The proposed plan consists of 42 recommendations and measures that can be grouped into five central themes: Expertise and multidisciplinarity; Collaboration and networking; Knowledge, information and awareness; Equity in access; and Governance and sustainability.

    Taken collectively, the proposed measures and recommendations seek to, by the year 2016, “…diagnose and to treat, in multidisciplinary expert settings, approximately 18.000 patients with a rare disease, in surplus of the current situation. These recommendations and proposals for measures will generate an extra cost for the health care budget, in addition to the efforts already being made today. The additional effort for these proposed measures is estimated to be 34.8 million Euro per year for the period 2012-2016. This means a total of 174 million Euro for the whole period of five years. Of the 42 proposed measures, two generate 68% of this cost. The recommendations foresee a gradual implementation over time of these two measures, making it possible to prevent a possible derailment of the budget.”

    All EU Member States are urged, via the Council Recommendation of 8 June 2009 on an Action in the Field of Rare Diseases to develop a national strategy for their rare disease patients by the end of 2013.
    Consult the Recommendations and Proposed Measures for a Belgian Plan for Rare Diseases

    UK health services to provide assessments for off-label medicinal use
    Off-label drug use has come under the spotlight in Europe following a scandal in France involving the widespread use of a product for an indication other than that which it had been authorised and which transpired in numerous deaths. However, off-label medicine use, which refers to the use of a medicinal product for an indication other than those for which it has received marketing authorisation, is critical in the field of rare diseases - an area that suffers from a serious lack of tested and authorised treatments. In the UK, the National Institute for Health and Clinical Excellence (NICE) will start commissioning expert assessments for off-label medicine use starting next spring. These assessments will not constitute formal guidance, but rather will provide “a summary of available evidence on selected unlicensed drugs to inform local decision-making”. A NICE press release on the topic observes that, “…Patients with rare diseases, such as certain cancers like lymphoma or autoimmune diseases, may have limited access to medicines as there are often not enough patients to run the clinical trials needed to develop a licensed drug. Some of these patients could benefit from treatment with unlicensed or off-label drugs”. According to the press release, the National Health Service (NHS) in England receives some 1000 specific requests for off-label use annually. The announcement for the off-label product assessments has been met with approval from the rare disease community. In the NICE press release, Andrew Wilson, Chief Executive of the Rarer Cancers Foundation, is quoted as saying: “This announcement is good news for patients with rare cancers and will help ensure all patients get access to good standards of care. No patient should be disadvantaged simply because they are unlucky enough to have a rare disease”.
    Consult the NICE press release

    Switzerland moves forward project to develop national strategy for reimbursing rare disease medicinal products
    In Switzerland, the Federal Office of Public Health is working on a project that will facilitate the reimbursement of rare disease medicinal products. According to a news source, a round table meeting held in September gave health professionals, members of the biopharmaceutical industry, and local government representatives the opportunity to exchange views. Amongst the topics broached were strategies for reimbursing products and evaluating their benefits, as well as ways to improve diagnosis, for which the French model of identifying and creating networks of expertise was evoked. Finally, the issue of negotiating prices for rare disease treatments was discussed, as well as the necessity for clinicians and researchers to collaborate to enhance the understanding of rare disease treatments. A second round table will be held early next year. The project should then be open for consultation later in the year. The issue of reimbursement for orphan drugs has been catalyzed in Switzerland by the case of a patient with myopathy whose treatment was deemed cost-prohibitive. The particular treatment is presently being reimbursed, under certain conditions related specifically to efficacy. Reimbursement is limited to one year after which it must again undergo evaluation.
    Other International News
    Human genetics congress provides venue to discuss technology advances and impact on rare disease patients and caregivers
    The 12th International Congress of Human Genetics was held in Montreal, Canada in mid-October, featuring a multitude of international speakers from all specialties of genetics and genomics and over 6500 participants all gathered to focus on recent developments in the rapidly evolving field that is crucial to the area of rare diseases of which a large majority are monogenic conditions. One interesting debate session addressed the Current and Emerging Sequencing Technologies: Changing the Practice of Medical Genetics. The session engaged debate around four central statements:
  • Targeted sequencing will remain the norm for diagnostic medical genetics because whole-exome or whole-genome sequencing will yield an excess of information that is useless, uninterpretable, or possibly damaging to the patient
  • Personal genome sequencing creates an unacceptable risk to the privacy of people
  • Cytogenetics will cease to be. Sequencing is the only future technology in diagnostic labs
  • Personal genomes will become incorporated in the standard of care for all of medicine. Therefore, medical genetics will disappear as a separate specialty

  • What emerged from this round table was the agreement that whole-genome sequencing is indeed a powerful tool useful to gaining insights into human genetics and to further characterise multifactorial diseases, but not yet ready as a diagnostic tool in genetic services. Thus research must continue in this area. The session panelists warned that the scientific community is not yet equipped to handle and interpret the enormous amount of data resulting from whole-genome sequencing, due in part to the fact that the correlation between genotype and phenotype is not linear. Great caution is needed in using this technology to diagnose patients. The direct-to-consumer policy of some companies was questioned as the difficulties in result interpretations could lead to misunderstanding that may cause unnecessary stress and worry. These issues were again the focus of discussion at the recent Eurobiomed Rare 2011 conference that was held in Montpellier, France in early November. Look for a full report of this event in the next issue of OrphaNews Europe.
    Regard the full programme of events from the 12th International Congress of Human Genetics


    Orphanet News
    New rare disease emergency guidelines in French and Portuguese
    Orphanet provides rare disease emergency care guidelines to be distributed to emergency and intensive care hospital units and also made available on the Orphanet website. New guidelines are now available in French for:

    Fabry disease (maladie de Fabry)

    New emergency guidelines are also available in Portuguese, translated via funding from Shire AG, for:

    Brugada syndrome (Síndrome de Brugada)
    Autoimmune polyendocrinopathy, type 1 (Poliendocrinopatia autoimune de tipo 1)


    New Syndromes

    Nasal speech and hypothyroidism are common hallmarks of 12q15 microdeletions
    The authors report three patients with a de novo overlapping microdeletion of chromosome bands 12q15q21.1. The deletions are about 2.5 Mb in size, with a 1.34-Mb common deleted region containing six RefSeq genes. All three patients present with learning disability or developmental delay, nasal speech and hypothyroidism.
    Read the PubMed abstract

    Eur J Hum Genet ; 1032-1037 ; October 2011
    Microtriplications of 11q24.1 are responsible for a highly recognisable phenotype
    While studying patients with unexplained intellectual disability, the authors identified two unrelated patients with de novo interstitial triplication of the 11q23.3q24.1 region. The patients share a common 1.8 Mb triplicated genomic segment within 11q24.1 associated with highly similar clinical features: characteristic facial phenotype, short stature with small extremities, keratoconus, overweight with hypercholesterolaemia, and intellectual disability with severe verbal impairment. The overlapping triplicated region contains 11 RefSeq genes and three microRNA related genes.
    Read the PubMed abstract

    J Med Genet ; 635-639 ; September 2011
    Leber congenital amaurosis as first sign of a syndrome in the peroxisome biogenesis disorder spectrum with PEX1 mutation(s)
    The authors describe two patients who presented initially with Leber congenital amaurosis (LCA). The first patient, aged 28 years and cognitively normal, is blind due to LCA, and has sensorineural hearing loss and an Arnold-Chiari I malformation. The authors identified the causal homozygous mutation in PEX1, c.2528G→A (p.Gly843Asp), a known disease gene and common mutation. This mutation was searched in a LCA cohort and a second patient was found. This patient had an only ocular phenotype (diagnosed as LCA) until age 18 months when she developed the systemic complications of severe peroxisome biogenesis disorder. She is compound heterozygous with another known PEX1 mutation [c.2098insT (p.Ile700Tyrfs42X)] on the second allele.
    Read the abstract

    J Med Genet ; 593-596 ; September 2011

    New Genes

    Choroideremia: a dominant mutation in RPE65 can cause the disease
    Read the PubMed abstract
    To read more about "Choroideremia"

    Eur J Hum Genet ; 1074-1081 ; October 2011
    Knobloch syndrome: ADAMTS18 proposed as a second KS gene
    Read the PubMed abstract
    To read more about "Knobloch syndrome"

    J Med Genet ; 597-601 ; September 2011
    Kearns-Sayre syndrome: RRM2B mutations found in one adult patient
    Read the PubMed abstract
    To read more about "Kearns-Sayre syndrome"

    J Med Genet ; 610-617 ; September 2011
    Leber congenital amaurosis: ALMS1, CNGA3, and MYO7A are three novel disease causing genes
    Read the PubMed abstract
    To read more about "Congenital Leber amaurosis"

    Hum Mutat ; Epub ahead of print ; 7 September 2011
    Methylmalonic acidemia-homocystinuria: inborn error of folate metabolism due to MTHFD1 mutations at cause in an infant
    Read the PubMed abstract
    To read more about "Methylmalonic acidemia - homocystinuria"

    J Med Genet ; 590-592 ; September 2011
    Mitochondrial myopathy with reversible cytochrome C oxidase deficiency: two families have mutations in TRMU
    Read the PubMed abstract
    To read more about "Mitochondrial myopathy with reversible cytochrome C oxidase deficiency"

    J Med Genet ; 660-668 ; October 2011
    Fatal infantile hypertrophic cardiomyopathy: mutations in NDUFAF1 (a mitochondrial complex I assembly factor) found in one case
    Read the PubMed abstract
    To read more about "Mitochondrial disease with hypertrophic cardiomyopathy"

    J Med Genet ; 691-697 ; October 2011
    Nonsyndromic mitochondrial sensorineural deafness: a mutation in mitochondrial tRNA His gene causes late-onset disease
    Read the PubMed abstract
    To read more about "Mitochondrial nonsyndromic sensorineural deafness"

    J Med Genet ; 682-690 ; October 2011
    Familial isolated clubfoot: PITX1 haploinsufficiency responsible over three generations in a family
    Read the PubMed abstract
    Hum Mol Genet ; 3943-3952 ; 15 October 2011
    Monocytopenia with susceptibility to infections: the syndrome is the result of GATA2 mutations
    Read the PubMed abstract
    To read more about "Monocytopenia with susceptibility to infections"

    Blood ; 2653-5; 2656-8 ; 8 September 2011
    Adrenocortical tumours: somatic alterations of AXIN2 identified in some patients
    Read the PubMed abstract
    To read more about "Adrenocortical adenoma"
    To read more about "Adrenocortical carcinoma"

    J Clin Endocrinol Metab ; E1477-E1481 ; September 2011

    Research in Action

    Fundamental Research
    Mucopolysaccharidosis type IIIB: induced pluripotent stem cells generated from young patient fibroblasts as a model
    Read the PubMed abstract
    To read more about "Mucopolysaccharidosis type 3"

    Hum Mol Genet ; 3653-3666 ; 15 September 2011
    Severe laminopathy diseases: mechanism and prevention of accumulation of unrepairable DNA damage in cultured fibroblasts
    Read the PubMed abstract
    To read more about "Lethal restrictive dermopathy"
    To read more about "Polysyndactyly-overgrowth syndrome"

    Hum Mol Genet ; 3997-4004 ; 15 October 2011
    Huntington disease: novel mechanism of Hsp70 chaperone-mediated prevention of polyglutamine aggregates in a cellular model
    Read the PubMed abstract
    To read more about "Huntington disease"

    Hum Mol Genet ; 3953-3963 ; 15 October 2011
    Neurofibromatosis type 1: mice lacking Nf1 in osteochondroprogenitor cells display skeletal dysplasia similar to patients
    Read the PubMed abstract
    To read more about "Neurofibromatosis type 1"

    Hum Mol Genet ; 3910-3924 ; 15 October 2011
    Holoprosencephaly: Noggin null allele mice exhibit a microform of the disease
    Read the PubMed abstract
    To read more about "Solitary median maxillary central incisor syndrome"

    Hum Mol Genet ; 4005-4015 ; 15 October 2011
    LGMD2H: common missense mutation D489N in TRIM32 leads to loss of the mutated protein in knock-in mice
    Read the PubMed abstract
    To read more about "Autosomal recessive limb-girdle muscular dystrophy type 2H"

    Hum Mol Genet ; 3925-3932 ; 15 October 2011
    Clinical Research
    Idiopathic pulmonary fibrosis: efficacy of a tyrosine kinase inhibitor in a phase 2 trial
    Read the PubMed abstract
    To read more about "Idiopathic pulmonary fibrosis"

    N Engl J Med ; 1079-1087 ; 22 September 2011
    Beta-thalassaemia intermedia: favorable changes with decitabine in a pilot study
    Read the PubMed abstract
    To read more about "Beta-thalassemia intermedia"

    Blood ; 2708-2711 ; 8 September 2011
    Haemophilia B: enhanced pharmacokinetic properties of a glycoPEGylated recombinant factor IX in a first human dose trial
    Read the PubMed abstract
    To read more about "Hemophilia B"

    Blood ; 2695-2701 ; 8 September 2011
    Persistent hyperinsulinaemic hypoglycaemia of infancy: lanreotide acetate may improve quality of life
    Read the PubMed abstract
    To read more about "Congenital isolated hyperinsulinism"

    J Clin Endocrinol Metab ; 2312-2317 ; August 2011
    ACTH-dependent Cushing syndrome: mitotane, metyrapone, and ketoconazole combination as an alternative to rescue adrenalectomy
    Read the PubMed abstract
    To read more about "ACTH-dependent Cushing syndrome"

    J Clin Endocrinol Metab ; 2796-2804 ; September 2011
    Genetic skeletal disorders: 2010 revision of the Nosology and Classification
    Read the PubMed abstract
    Am J Med Genet A ; 943-968 ; May 2011
    Adenosine deaminase deficiency: myeloid dysplasia and bone marrow hypocellularity are associated with the disease
    Read the PubMed abstract
    To read more about "Severe combined immunodeficiency due to adenosine deaminase deficiency"

    Blood ; 2688-2694 ; 8 September 2011
    Congenitally uncorrected transposition of the great arteries: neuropsychological assessment and brain imaging of adolescents
    Read the PubMed abstract
    To read more about "Congenitally uncorrected transposition of the great arteries"

    Circulation ; 1361-1369 ; 20 September 2011
    Congenital hypothyroidism: memory weakness may be linked to compromised hippocampal development in children and adolescents
    Read the PubMed abstract
    To read more about "Congenital hypothyroidism"

    J Clin Endocrinol Metab ; E1427-E1434 ; September 2011
    Gene Therapy
    Autosomal recessive dystrophic epidermolysis bullosa: proof of principle for ex vivo gene therapy in dogs
    The authors used genetically engineered recessive dystrophic epidermolysis bullosa (RDEB) dog keratinocytes to generate autologous epidermal sheets subsequently grafted on two RDEB dogs carrying a homozygous missense mutation in the collagen type VII gene. Transplanted cells regenerated a differentiated and vascularised auto-renewing epidermis progressively repopulated by dendritic cells and melanocytes. No adverse immune reaction was detected. However, only one of the two dogs kept the grafted epidermis firmly adhered to the dermis throughout the 24-month follow-up. Persistent success of gene therapy was linked to highly efficient transduction of epidermal stem cells (100% efficient transduction was noted in the successfully treated dog, versus 65% in the second dog).
    Read the PubMed abstract

    To read more about "Autosomal recessive dystrophic epidermolysis bullosa, Hallopeau-Siemens type"
    To read more about "Autosomal recessive dystrophic epidermolysis bullosa, non-Hallopeau-Siemens type"

    J Invest Dermatol ; 2069-2078 ; October 2011
    Duchenne muscular dystrophy: improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction
    The authors utilised recombinant adeno-associated virus (rAAV) serotype 9, which can be administered systemically with excellent cardiac tropism, to deliver microdystrophin gene to mdx mice. The myocardium was extensively transduced with microdystrophin to significantly prevent the development of fibrosis, and expression persisted for the duration of the study. Intraventricular conduction patterns were also corrected. Furthermore, BNP (brain natriuretic peptide) and ANP (atrial natriuretic peptide) levels were reduced to normal, suggesting the absence of cardiac dysfunction. In aged mice, prevention of ectopic beats as well as echocardiographic amelioration was also demonstrated with improved exercise performance.
    Read the PubMed abstract

    To read more about "Duchenne muscular dystrophy"

    Gene Therapy ; 910-919 ; September 2011
    Therapeutic Approaches
    Spinal muscular atrophy: inter- and intra-patient variability in cell response to drugs that upregulate SMN expression
    Read the PubMed abstract
    To read more about "Proximal spinal muscular atrophy"

    Eur J Hum Genet ; 1059-1065 ; October 2011
    Epidermolytic epidermolysis bullosa: therapeutic perspectives with specific siRNA and chemical chaperones
    Read the PubMed abstract
    To read more about "Epidermolytic epidermolysis bullosa"

    Journal of Investigative Dermatology ; 1684-1691 ; August 2011
    Journal of Investigative Dermatology ; 2079-2086 ; October 2011

    Patient Management and Therapy

    Turner syndrome: standardised multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women
    The authors conducted an observational study at a multidisciplinary care unit for adult women with Turner syndrome in the Netherlands. 150 women (mean age: 31.0 ± 10.4 yr; karyotype 45,X: 47%) were consulted by an endocrinologist, a gynecologist, a cardiologist, an otorhinolaryngologist, and when indicated, a psychologist. Thirty percent of patients currently lacked medical follow-up, and 15% lacked estrogen replacement therapy in the recent last years. The following disorders were newly diagnosed: bicuspid aortic valve (n = 13), coarctation of the aorta (n = 9), elongation of the transverse aortic arch (n = 27), dilation of the aorta (n = 34), osteoporosis (n = 8), osteopenia (n = 56), renal abnormalities (n = 7), subclinical hypothyroidism (n = 33), celiac disease (n = 3), glucose intolerance (n = 12), dyslipidemia (n = 52), hypertension (n = 39), and hearing loss warranting a hearing aid (n = 8). Psychological consultation was needed in 23 cases.
    Read the PubMed abstract

    To read more about "Turner syndrome"

    J Clin Endocrinol Metab ; E1517-E1526 ; September 2011
    Idiopathic pulmonary fibrosis: international evidence-based guidelines for diagnosis and management
    This document is a collaborative effort of the American Thoracic Society (ATS), the European Respiratory Society (ERS), the Japanese Respiratory Society (JRS), and the Latin American Thoracic Association (ALAT). It contains sections on definition and epidemiology, risk factors, diagnosis, natural history, staging and prognosis, treatment, and monitoring disease course. For each diagnosis and treatment question, the committee graded the quality of the evidence available and made a recommendation. It is emphasized that clinicians must spend adequate time with patients to discuss patients’ values and preferences and decide on the appropriate course of action.
    Read the PubMed abstract

    To read more about "Idiopathic pulmonary fibrosis"

    Am J Respir Crit Care Med ; 788-824 ; 15 March 2011
    Three new Clinical Utility Gene Cards available
    EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases. The European Journal of Human Genetics has published three new Clinical Utility Gene Cards for:
    Menkes disease
    Loeys-Dietz syndrome (TGFBR1/2) and related phenotypes
    Alström syndrome


    Orphan Drugs

    12 positive opinions recommending orphan designation at the October COMP meeting including a first for Leigh syndrome
    The European Medicines Agency Committee for Orphan Medicinal Products (COMP) adopted 12 positive opinions recommending orphan designation at the October 2011 COMP meeting, including a first time ever positive opinion on orphan designation for the treatment of Leigh syndrome, for which no authorised treatments exist in the EU. The 12 positive opinions recommending orphan designation are for the treatment of:

    - adjunctive treatment to cytotoxic therapy in acute myeloid leukaemia
    - Leigh syndrome
    - polycythaemia vera
    - idiopathic pulmonary fibrosis
    - Leber congenital amaurosis type 4
    - cystic fibrosis
    - sickle cell disease
    - Friedreich ataxia
    - diagnosis of folate receptor status in ovarian cancer
    - pancreatic cancer
    - Hodgkin lymphoma
    - ovarian cancer

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

    What is the impact of orphan drugs on premature mortality?
    A new study published in the European Journal of Health Economics considers the impact of orphan drugs on premature mortality. Working with longitudinal, disease-level data from the USA and from France, the authors calculate the extent to which new drug approvals have reduced premature mortality from rare diseases by comparing the actual decline in premature mortality to the decline (or increase) that would have occurred in the absence of new drug approvals. The study finds that "Both the US and French estimates indicate that, overall, premature mortality from rare diseases is unrelated to the cumulative number of drugs approved 0-2 years earlier but is significantly inversely related to the cumulative number of drugs approved 3-4 years earlier. This delay is not surprising, since most patients probably do not have access to a drug until several years after it has been launched. Thus, it can be concluded that earlier access to orphan drugs could result in earlier reductions in premature mortality from rare diseases". Furthermore, the study estimates indicate that, for the USA, potential years of life lost to rare diseases before age 65 (PYLL65) declined at an average annual rate of 3.3%. In the absence of lagged new drug approvals, PYLL65 would have increased at a rate of 0.9%. The reduction in the US growth rate of PYLL65 attributable to lagged new drug approvals was 4.2%. Meanwhile, in France PYLL65 declined at an average annual rate of 1.8%. In the absence of lagged new drug approvals, the estimates imply that PYLL65 would have declined at a rate of 0.6%. The reduction in the French growth rate of PYLL65 attributable to lagged new drug approvals was 1.1%.
    Consult the PubMed abstract

    New thalassaemia product approved in the USA and increased warnings for renal cell carcinoma product
    In the USA, the Food and Drug Administration (FDA) has approved Ferriprox (deferiprone) from ApoPharma Inc to treat iron overload due to blood transfusions in patients with thalassaemia who had an inadequate response to prior chelation therapy.

    In other news, the FDA announced changes in the labelling of bevacizumab (Avastin, Genentech, Inc.) to include information regarding the risk of ovarian failure, osteonecrosis of the jaw, risk of venous thromboembolic event (VTE) and bleeding in patients receiving anticoagulation therapy after first VTE event. Avastin has marketing authorisation for rare disease renal cell carcinoma, as well as for non-small-cell lung cancer, and colorectal neoplasms in both the European Union and the USA and also for glioblastoma in the USA.


    Applications for rare pulmonary disease award to open soon
    Through the financial support of GlaxoSmithKline (GSK) the European Respiratory Society (ERS) offers an award of €12,000. The award is given in recognition of advances and research in the field of rare pulmonary diseases. The award is mainly intended to support a project in the field of rare pulmonary diseases. The application period will open in December and will have a deadline of 23 February 2012.

    Candidate criteria include ERS membership and research work in the field of a rare pulmonary disease. The candidate will be evaluated based on past achievements and the potential of the proposed research programme.
    Learn more


    Courses & Educational Initiatives

    ESH-ENERCA Training Course: Diagnosis and Management of Very Rare Anaemias
    This two-day ENERCA-ESH training course on rare red blood cell disorders will be held in Paris, France on 3-4 February 2012. The course aims at promoting harmonisation of procedures for clinical and biological diagnosis, as well as management and follow-up of patients with very rare red cell disorders, including red blood cell membrane disorders and enzymopathies, congenital dyserythropoietic anaemias, and other rare disorders of the red blood cell. The course should be of interest for biologists, haematologists, paediatricians and trainees in haematology.
    For further details

    European Cytogeneticists Association Course
    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 2012 course (scheduled from 20-28 February) is now available.
    For further details

    Tenth European Course on the Evaluation of Medicinal Products in Children
    Organized with the European Society for Developmental, Perinatal & Paediatric Pharmacology, and the University Rene Descartes Paris V, and taking place from 21-24 February and 27-30 March 2012, modules for this seminar include: Specific aspects of paediatric pharmacology; Issues relating to trials and drug use in children; Drug development and post-marketing surveillance; Pre/peri-natal drug evaluation and use; Paediatric Investigation Plan design; and more.
    For further details

    Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis
    The Goldrain Prenatal Genetic Diagnosis course, tentatively scheduled from 6-12 October 2012 at the Goldrain Castle in South Tyrol (Italy), is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other's field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination. The 2012 Clinical Cytogenetics course has not yet been announced.
    For further details

    Master of Science in Haemoglobinopathy
    A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy - such as counsellors, clinical psychologists, nurse specialists and midwives.
    For further details

    Orphan Academy 2012 Programme
    The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
    For further details

    EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
    The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
    For further details


    What's on Where?

    Sixth European Workshop on Immune-Mediated Inflammatory Diseases
    Date: 23-25 November 2011
    Venue: Nice, France

    The programme for this event includes sessions on "Lessons from monogenic diseases" including Omenn syndrome; L-1 blockade in inherited fever syndromes; Immune-mediated muscle wasting and more.
    For further details

    6th Eastern European Conference for Rare Diseases and Orphan Drugs
    Date: 24-26 November 2011
    Venue: Istanbul, Turkey

    The general objective of the conference Eastern European Conference for Rare Diseases and Orphan Drugs is to discuss the development of policy on Rare Diseases and Orphan Drugs in Eastern European countries in comparison with the EU policy. The following plenary sessions and parallel workshops topics include: European Union Policy for Rare Diseases, Eastern European Countries Policies for Rare Diseases, Best Practices on Rare Diseases, Networks & Centers of Reference for Rare Diseases, Challenges in Diagnosis, Challenges in Treatment, Role of Industry for Orphan Drugs Development and Access to Orphan Drugs, Awareness of Medical Professionals and Health Authorities, Challenges to Patients and Families, Empowerment of Patients, Organising Patients and Families, and Awareness of Patients and the Society.
    For further details

    Sanfilippo Foundation Switzerland International Congress
    Date: 8-10 December 2011
    Venue: Geneva, Switzerland

    Research toward a treatment is the theme of this conference focusing on innovative research to treat mucopolysaccharidosis.
    For further details

    2nd Annual Optimising Orphan Drug Development Conference
    Date: 18-19 January 2012
    Venue: Lyon, France

    This commercial event will focus on how to gain access to new geographically markets. It will cover updates on pricing and reimbursement strategies, how to improve clinical trial development plans and examine the challenges faced with paediatric drug development. This conference will also address the role of patient advocacy groups and how to run patient registries efficiently whilst examining novel data capture methods. Understanding how to translate data to clinical trials will accelerate orphan drug development to market, gain market exclusivity thereby keeping companies ahead of competitors.
    For further details

    Rare Cancers Conference: Improving the Methodology of Clinical Research
    Date: 10 February 2012
    Venue: Brussels, Belgium

    The European Society for Medical Oncology and Rare Cancers Europe have joined forces to present the first Conference addressing the scientific and educational needs of relevant stakeholder groups concerning challenges and potential solutions in the field of clinical research on rare cancers.
    For further details

    VII International Conference on Rare Diseases and Orphan Drugs (ICORD 2012)
    Date: 4-6 February 2012
    Venue: Tokyo, Japan

    A global meeting on international cooperation and public health policies focusing on research, diagnosis, development of and access to treatment and care for rare diseases. The VII ICORD Conference will offer a platform for the exchange of perspectives for medical and healthcare professionals, patients and patients’ groups, basic and clinical researchers, policy-makers, government officers and pharmaceutical, biotechnology and medical device industries.
    For further details

    International Congress on Research of Rare and Orphan Diseases
    Date: 29 February - 2 March 2012
    Venue: Basel, Switzerland

    The Swiss-based Blackswan Foundation and Gebert Ruf Stiftung Foundation, both active in supporting research activities in Rare Diseases, are preparing an international congress of which the main topics will include Gene and cell therapy; Stem cells; Diagnostics; Therapeutic applications; and Genomic disorders. The congress will be open to scientific researchers, specialized scholars, professionals and officials.
    For further details

    Second ASID Congress of the African Society for Immunodeficiencies
    Date: 8-11 March 2012
    Venue: Hammamet, Tunisia

    This second congress - postponed from its original 2011 date - will be an excellent opportunity to strengthen the capacity of colleagues all over the continent to better diagnose and manage patients with PIDs. The commitment and contribution of international experts, societies and associations to this process is highly appreciated.
    For further details

    13th International Conference on Neuronal Ceroid Lipofuscinosis and 1st Worldwide Meeting of Batten Disease Int'l Alliance
    Date: 28-31 March 2012
    Venue: London, England

    This is the only forum that brings together those with interests in basic science and clinical care for this group of devastating diseases. A new dimension is added this year by bringing together the newly formed Batten Disease International Alliance (BDIA) for its first worldwide meeting. Deadline for abstract submission: 30 November 2011.
    For further details

    Fourth International Meeting on Primary Central Hypoventilation Syndromes
    Date: 13-14 April 2012
    Venue: Warsaw, Poland

    The fourth international CHS meeting will be organized by the European CHS Consortium and will address physicians, researchers, families and all persons involved or interested in Central Hypoventilation Diseases.
    For further details

    CILIA 2012 - Cilia in Development and Disease
    Date: 16-18 May 2012
    Venue: London UK

    Sessions will cover: Clinical aspects of ciliopathies and genotype/phenotype prediction; Structure and function of cilia; Role of cilia in development and ciliary signalling modules; Role of cilia in disease – human genetics and animal models; Translational therapy and current and future ciliotherapeutics; and more.
    For further details

    6th European Conference on Rare Diseases & Orphan Products
    Date: 23-25 May 2012
    Venue: Brussels, Belgium

    The conference is structured in such a way as to demonstrate the importance of EU actions in the field of rare diseases and review progress to date. With its plenary and parallel sessions addressing specific issues, knowledge-sharing is encouraged, the exchange of real experiences and best practices are integrated into the programme, cooperation and networking are stimulated and awareness is increased while ensuring continuity of action and prevention of duplication of efforts. Less advanced regions in this field will benefit from experience sharing with other areas in Europe. The Opening & Plenary Sessions will be interpreted into six languages: English, French, Spanish, German, Dutch and Russian.
    For further details

    European Human Genetics Conference 2012
    Date: 23-26 June 2012
    Venue: Nurnberg, Gemany

    A rich programme awaits participants. Symposia include: The molecular basis of facial malformations; Mechanisms and consequences of chromosomal/genetic mosaicism; Primary microcephaly; and much more. Educational sessions include Next-generation sequencing diagnostics; Trinucleotid repeat disorders and more. Plenary sessions include: Targeted pharmacological therapies in genetic disorders (with presentations on Marfan, tuberous sclerosis complex and fragile X); and more.
    For further details

    First International Symposium on the Ehlers-Danlos Syndrome
    Date: 8-11 September 2012
    Venue: Ghent, Belgium

    Topics include natural history; clinical aspects; updated nosology; diagnostics guidelines; therapeutic and management strategies; animal models, and more.
    For further details

    3rd Pan-European Conference on Haemglobinopathies and Rare Anaemias: Towards the Future
    Date: 25-26 October 2012
    Venue:Limassol, Cyprus

    The Thalassaemia International Federation is delighted to announce the organisation of the 3rd Pan-European Conference, held under the auspices of the Cyprus Presidency and in close collaboration with the Cyprus Ministry of Health. The conference will bring together stakeholders to discuss avenues of action to tackle the growing public health burden of chronic and rare diseases in Member States and the EU.
    For further details


    Press & Publications
    Faith and hope: one man’s response to a fatal rare disease

    Gib’s Odyssey: A Tale of Faith and Hope on the Intracoastal Waterway leaves the reader pondering whether they are making the most of their life. Gilbert Alexander Peters certainly made the most of his – especially after receiving the news that he had amyotrophic lateral sclerosis (ALS), a rare, fatal neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurons in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. Gib, as he was called by friends and family, took the diagnosis as an invitation to do what mattered most to him. In his case, this meant a challenge – both to himself and to the disease itself – to do something he truly loved: boating. With the spectre of death looming in the background, Gib prepared his beloved motorboat Ka Ching for the voyage of a lifetime: a solitary journey up the intracoastal waterway from the southern tip of Florida to New York and back. Actually, Gib was not completely alone. He took two companions aboard: kittens Faith and Hope. Gib’s Odyssey, sensitively rendered by his treating neurologist, Dr. Walter G. Bradley, traces one man’s courageous response to the news of a death sentence, as Gib sets sail with ALS following closely in his wake. The emails that Gib sent during his journey (in the end pecking them out with the only finger still capable of movement), offer a first-person account of the struggles and triumphs of Gib’s final voyage. Manning a motorboat alone up the Atlantic is challenge enough for a healthy individual, and thus the reader follows with bated breath Gib’s journey … and the progression of the disease which takes his speech, the ability to swallow, the use of his right, then left, arm, and finally, his legs and lungs. We know how this story is going to end – Gib has already specified that he does not want the trachetomy and artificial ventilation that allows some ALS sufferers (such as noted astrophysicist Stephen Hawking) to continue living for years, even decades.

    If Gib reminds the reader of one thing, it is this: It is the journey, not the destination, which matters most. Braving storms, accidents, engine failures, and a kitten overboard (which helps Gib understand what it means to his loved ones to know they will soon lose him), Gib shows us what it means to have the courage and determination to make each day truly count.

    Title: Gib’s Odyssey: A Tale of Faith and Hope on the Intracoastal Waterway
    Author: Walter G. Bradley, MD
    Publisher: Globe Pequot Press
    ISBN-13: 978-0762764167


    Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
    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, Kate Bushby, Catherine Berens, Helena Kaariainen, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Christophe Roeland

    EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Radka Tincheva (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), Sveinn Magnusson (Iceland), John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Jonas Bartlingas (Lithuania), Yolande Wagener (Luxembourg), Maria-Louise Borg (Malta), Harry Seeverens (Netherlands), Stein Are Aksnes (Norway), Jakub Adamski (Poland), Luis Nunes (Portugal), Ana Maria Vladareanu (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), Michael Soop (Sweden), Sabina Gallati (Switzerland), Edmund Jessop (UK)
    EUCERD ECDC Representative: Andrew Amato
    EUCERD Patient Organisation Representatives: Dorica Dan, Torben Gronnebaek, Yann Le Cam, Christel Nourissier
    EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
    EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
    EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
    EUCERD European Commission Participants: Catherine Berens, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Antoni Montserrat Moliner, Christophe Roeland, Stefan Schreck, Kerstin Westermark (EMA-COMP)
    Orphanet Partner Country Representatives: Tamara F. Sarkisian (Armenia), Yvonne Zurynski (Australia), Till Voigtlander (Austria), Herwig Jansen (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann-Spangenberg (Germany), Michael Petersen (Greece), Sandor Janos (Hungary), Andrew Green (Ireland) Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbane (Lebanon), Viadutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequieros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Desirée 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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