25 March 2009 print
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Globalisation at its best: the official day for rare diseases expands to five continents

The Second International Rare Disease Day expanded from being a European event just one year earlier to embrace Australia, Canada, China, Latin America, Taiwan and the USA. Organised by the European Organisation for Rare Diseases (EURORDIS) in tandem with almost 20 rare disease alliances, the event has now spread to five continents, with activities designed to raise awareness and lobby for policies carried out in 29 different countries.

The last day of February has been officially designated as International Rare Disease Day by a growing number of countries, and a variety of events unfurled throughout the week leading up to the date. Media campaigns, marches, fund raisers, conferences, and debates were organised and executed throughout the world, significantly raising awareness for the rare disease cause. Besides the patient organisations, representatives from government, medicine, the biopharmaceutical industry, and academia participated in an array of different events.

The day presented the occasion to move forward policy development for some countries. Some examples include: patient representatives met with the national leader in Croatia; Spain organised activities at the Senate; Rare Disease UK, a coalition of patient charities, medical professionals and industry representatives, pressed Health Ministers to move forward action on the EU Council proposal to develop a national plan for rare diseases in the United Kingdom; and Bulgaria and Portugal revealed their recently adopted national rare disease plans.

The official Rare Disease Day website offers a country-by-country summary of the events planned in each country.


Spotlight on...
The Committee for Orphan Medicinal Products gets ready to blow out one hundred candles!

The orphan medicinal product regulation (Regulation (EC) No 141/2000) was adopted in December 1999 and came into force in the European Union (EU) in 2000. Nine years after its implementation, the Committee for Orphan Medicinal Products (COMP) will be celebrating its 100th meeting in April.

The Orphan Drug Regulation addresses the need to offer incentives for the development and marketing of drugs to treat, prevent, or diagnose rare conditions; without such incentives, the cost of developing and marketing products for these disorders would not be recovered by sales. The Regulation delineates the designation criteria, outlines the procedure for designation, and provides for incentives for products receiving an orphan designation. The incentives contained in the legislation aim to assist sponsors receiving orphan drug designations in the development of medicinal products with the ultimate goal of providing medicinal products for rare diseases to patients.

Orphan designation can be based on a number of factors: the prevalence of the condition; the return generated by the product too insufficient to justify investment; the severity of the condition; and the existence of alternative products. To receive designation, a product must target a life-threatening or chronically debilitating condition that affects no more than five in 10,000 persons (which currently corresponds to about 250,000 persons in the EU). Many rare conditions have a much lower prevalence.

Alternative to the rarity of the condition, sponsors can also apply if they are able to justify that without incentives the development costs of the product will not be recovered by the return obtained once the product is on the market. Any application for orphan drug designation must also describe all authorised methods of treatment (or diagnosis or prevention) existing for the orphan indication being applied for; in cases where authorised products already exist for the condition, the sponsor is asked to justify what the significant benefit would be for patients who would receive the proposed orphan product. What would be the clinically relevant advantage for patients if the proposed orphan product is marketed, or how would the drug contribute to their care? Normally this criterion is assessed at a very early stage in the drug development process, therefore at the time of designation the arguments are usually based on assumptions that will have to be confirmed at the time of marketing authorisation, when efficacy and safety data are available.

The EMEA is responsible for orphan drug designation through its Committee for Orphan Medicinal Products (COMP), which is comprised of health professionals representing each of the Member States, three patient representatives, and three representatives nominated by the EMEA. The Committee meets once a month and its responsibilities include the assessment of applications for orphan designation, the adoption of opinions on designation, advising the European Commission (EC) on policy relating to orphan medicines, assisting the EC in liaising internationally on matters relating to orphan medicinal products, and assisting the EC in drawing up detailed guidelines. The COMP is presently chaired by Professor Kerstin Westermark (Sweden) and co-chaired by Ms Birthe Byskov Holm (Patient Representative, Denmark). The COMP was pioneer in including patient representatives as full members and the experience has illustrated the great added-value of this collaboration, which contributes to the quality of the opinions adopted for orphan designation.

The achievements of the committee after 100 meetings can be summarised by the 634 positive opinions on orphan designation adopted so far from the 910 applications submitted for designation. The success rate for applications is almost 70%. The number of applications that currently receive orphan designation in 60 days, therefore without needing further clarification, is approximately 70%. With regard to the therapeutic areas attracting most designations, oncology has been the most represented with more than 40% of positive opinions on designation, followed by products for the musculoskeletal and nervous system (12%) and cardiovascular and respiratory systems (11%). Importantly, of the total number of positive opinions adopted, 64% are for conditions with prevalence lower than three in 10,000 persons. The Committee has received many applications for innovative products and has designated, amongst others, fusion proteins, monoclonal antibodies, cell and gene therapy products, and oligonucleotides to be developed for the treatment of rare diseases.

The development of orphan medicinal products is supported by incentives for development and placement on the market as provided for in the Orphan Regulation. Protocol Assistance, is provided by the Scientific Advice Working Party in collaboration with the COMP. Protocol assistance offers advice on the development of orphan drugs with regards to regulatory, quality, safety and efficacy issues.

The Committee is committed to continuing its work on orphan medicinal product designation and stimulating the development and placing on the market of such medicines. In the near future the COMP will be working on the preparation of the tenth anniversary of the adoption of the Regulation and on the assessment of its achievements.


EU Policy News
The value of ehealth tools – ideal for sharing rare disease expertise and resources - are reiterated in the Prague Declaration
An outcome of the ministerial conference entitled eHealth for Individuals, Society, and Economy that took place in Prague from 18–20 February was the adoption of the Prague Declaration on eHealth and a call for action on building an eHealth area for European citizens. The principal objective of the Prague Declaration "is to sum up the current state of the Europe-wide effort to use information and communication technologies (ICT) in healthcare for the benefit of patients as well as economic efficiency of the health sector. It also aims to determine further steps to be taken at the level of Member States as well as European institutions. At the same time, a common European eHealth area should be built, where individual national systems will be able to communicate with one another. Integrating eHealth solutions into national health strategies of the Member States will also be of great importance". The Prague Declaration was prepared in cooperation with the EU Member States. The ministerial conference targeted the various impacts of the eHealth solutions and processes. Amongst the presentations, ICT tools for rare diseases demonstrated how rare diseases provide a perfect example of the relevance of ICT tools in improving access to services and providing information at the European level. This presentation demonstrated the value of the various ehealth applications Orphanet has on offer for patients, health professionals, researchers, policy makers, and industry, across Europe and beyond. Other EU-funded rare disease electronic informational projects were cited including ECORN-CF, a shared knowledge database answering patient and professional queries on cystic fibrosis, and DYSCERNE, which provides an electronic forum for experts to submit cases of difficult-to-classify developmental anomalies.
Consult the Prague Declaration

European biobank working group issues recommendations for rare diseases
In February 2008, the Biobanking and Biomolecular Resources Research Infrastructure (BBMRI) launched to create a broadly accessible pan-European network of existing and de novo biobanks and biomolecular resources for global biomedical research. Such harmonisation is particularly crucial to rare disease research, which inherently has small sample pools from which to draw. BBMRI’s rare disease working group met in Munich last December and defined a preliminary set of recommendations:
  • Biobanks are highly relevant for rare disorders. While rare disease biobanks have many commonalities with other biobanks, they face additional challenges due to the rarity and the diversity of the conditions and biomaterials
  • It is the quality of the biomaterials and of the associated information rather than their quantity (number of samples) that is critical in rare disease biobanking
  • The adoption by biobanks of an appropriate disease coding system that accommodates all rare disorders, such as the nomenclature developed by Orphanet, is needed
  • Active participation and benefit sharing with patients and patient organisations is pivotal in rare disease biobanking. The Telethon biobanks (Italy) may serve as a prototype for networking rare disease biobanks on a national level, while EuroBioBank may be a prototype for networking rare disease biobanks on a European level
  • Rare disease biobanks have common objectives with BBMRI and recognise BBMRI as an important mechanism to secure the long-term sustainability of biobanks in Europe
  • Rare disease biobanks may provide experience and advanced solutions to BBMRI, some of which may be applicable to other biobanks.

    European Commission’s Policy Officer for Rare Diseases gets royal treatment in Spain

    On 10 March, General Directorate Health and Consumer Protection Policy Officer for Rare Diseases Dr. Antoni Montserrat, received recognition as “Rare Diseases Ambassador in Europe”. The award was bequeathed by Her Royal Highness Doña Leticia, Princess of Asturias, Spain, during the celebration of the International Rare Diseases Day hosted by the Spanish Federation of Rare Diseases (FEDER) at the Spanish Senate. FEDER chairman Moises Abascal was also awarded during the event, which was chaired by the Princess of Asturias, and representatives from the Ministries of Health and Education, the Senate and FEDER. The award ceremony is proof of the recognition rare diseases are receiving at the political level in Spain. Indeed, the government has demonstrated its support for the national strategy on rare diseases along with the creation of an organisational body within the state administration whose main mission would be the development and coordination of a national strategy.

    Rare disease patient representatives are part of EMEA’s Paediatric Committee
    As part of Paediatric Regulation (EC No 1901/2006), which came into effect in January 2007 to stimulate research and development of medicines for use in children, ensure that medicines for children are appropriately tested and authorised, and improve information availability, the Paediatric Committee (PDCO) was developed within the European Medicines Agency in July 2007 to provide scientific opinions on medicines intended for use in children. Orphan medicines represent 17% of all PDCO applications. The Paediatric Committee is composed of five CHMP members, representatives from each EU member state, three healthcare professionals, and three patient representatives, one of which was accorded to the European Organisation for Rare Diseases (EURORDIS). There are also alternative committee members for each of these roles. Thus, EURORDIS member Tsveta Schyns-Liharska is one of the PDCO patient representative. The mother of a child with rare disorder alternating hemiplegia, she possesses a background in molecular science and genetic research. The alternate appointee to this position is EURORDIS member Karen Aiach, mother of a child with Mucopolysaccharidosis type III (Sanfilippo disease), who founded the Sanfilippo Alliance in 2005 to promote drug research for the disorder.
    View the PDCO list of members


    National & International Policy Developments
    Newborn screening expands in Denmark and England
    Denmark’s newborn screening programme has for decades been limited to phenylketonuria and hypothyroidism. Now, the health authorities have decided to add testing for 15 more inborn errors of metabolism to the Danish programme. Furthermore, the timing for drawing the blood samples (done by heel-prick) will be brought forward from five days to within 48-72 hours following birth, allowing for the earlier intervention of affected babies. Meanwhile newborn screening for Medium Chain Acyl CoA Dehydrogenase Deficiency (MCADD), introduced in 2007 via a pilot study involving six UK centres screening more than 700,000 babies, is being extended to all newborns in England this year.
    German revision of pharmaceutical law shifts compassionate use costs to industry
    In Germany, as in many other countries, it has been possible to administer medicinal products for severely ill patients, even when such products are still undergoing clinical testing. This practice is known as “Compassionate use” and has saved the lives of many rare disease patients. While until now, the German state insurance has paid the cost of compassionate use treatment, the German government is now revising this aspect of the law as part of the fifteenth general revision of the legislation governing medicinal products. Under the revision of Paragraph 21.2.6, the compassionate use of medicinal products would have to be funded by the pharmaceutical company developing the treatment. A majority of novel orphan medicinal products are developed by small- and medium-sized enterprises, most of which could not afford the costs of distributing products for compassionate use. Germany’s parliament still has to vote on the revised legislation. There thus still remains a window through which to make heard the voices of patients suffering from rare diseases.
    Yes he did! – President Obama reverses embryonic stem cell federal funding prohibition
    On 9 March, newly-elected USA President Barack Obama signed an executive order ending restrictions on earmarking federal dollars for embryonic stem cell research. In an address, President Obama commented: “We will bring the change that so many scientists and researchers; doctors and innovators; patients and loved ones have hoped for, and fought for, these past eight years: we will lift the ban on federal funding for promising embryonic stem cell research”. President Obama called for the separation of political ideology from scientific facts. Embryonic stem cell treatment holds promise for the spectrum of rare disorders that are genetic in origin, as well as many other conditions, such as neurodegenerative diseases. However, the 1996 Dickey-Wicker amendment, banning funding for research that involves the destruction, injury or death of a human embryo, remains intact in the USA. This, coupled with advances in pluripotent cell development from other sources such as skin cells, mean that the funding reversal may have less impact than originally thought. However, just one day after the reversal was signed, Harvard University approved a new undergraduate concentration in Human Development and Regenerative Biology within its Department of Stem Cell and Regenerative Biology.

    Ethical, Legal & Social Issues
    New report evokes the challenges older parents face in caring for disabled adult offspring
    A report prepared by researchers at Queen’s University Belfast (Ireland) focuses on older parents caring for their disabled adult progeny. This population, for whom the average age is 65 years, reported a stress level twice that of the general population. What the future holds: Older people caring for adult sons and daughters with disabilities was drawn from interviews from 29 parents caring for 27 adult-age children including those diagnosed with Prader-Willi syndrome, phenylketonuria, autism, Cohen syndrome, and learning disabilities, amongst other disorders. Despite reporting high levels of both commitment and love for their adult-aged children, the older parents also experienced a lack of respite and support. Amongst the greatest challenges the parents reported were coping with difficult behaviour, including physical aggression, and trying to meet the social needs of the adult offspring. For 97% of participants, caring was a full-time job; and for 86%, physical care constituted part of their tasks. Some 72% of the participants “had not considered making long-term plans for the future care of their sons or daughters with disabilities” and 48% admitted having no adequate substitute care arrangements should the principal caregiver fall ill. The report concludes with a set of recommendations that would bring support to older adults caring for their adult sons and daughters with disabilities, including early interventions designed to enhance the life skills of the disabled adults; appropriate alternative accommodations; and evidence-based training for service providers working with the families. These considerations are critical as many rare diseases patients are experiencing longer life expectancies due to better understanding and management of disorders.
    Consult the report


    Orphanet News
    New Texts
    New Orphan Journal of Rare Diseases publications
    Charcot–Marie–Tooth disease (published in the European Journal of Human Genetics, in association with Orphanet)

    New Syndromes
    Dysferlinopathy: a new phenotype with congenital onset
    The authors report two patients with a new phenotype of dysferlinopathy presenting as congenital muscular disease. Both patients showed weakness in proximal lower limbs and neck flexor muscles at birth. The presence of normal CK levels during the first years should be noted. Dysferlin gene analysis revealed a mutation in a homozygous state in both siblings. In the majority of dysferlinopathy cases, the disease presents at 20 years, with a ten-year-old being the youngest patient observed. This new congenital phenotype widens the clinical spectrum of dysferlin myopathies.
    Read the PubMed abstract

    Neuromuscul Disord ; 21-25 ; January 2009
    ECO syndrome: a newly observed endocrine-cerebro-osteodysplasia condition
    Six consanguineous infants in an Old Order Amish pedigree were observed to be affected with endocrine-cerebro-osteodysplasia (ECO). ECO is a previously unidentified neonatal lethal recessive disorder with multiple anomalies involving the endocrine, cerebral, and skeletal systems. Autozygosity mapping and sequencing identified a previously unknown missense mutation in ICK, encoding intestinal cell kinase.
    Read the PubMed abstract

    Am J Hum Genet ; 134-147 ; February 2009

    New Genes
    Woolly hair/hypotrichosis: mutations in the lipase H gene underlie the autosomal recessive form
    Woolly hair (WH) is characterised by the presence of fine, tightly curled hair, which can be difficult to comb. WH can appear as a symptom of some systemic diseases, or without associated findings (nonsyndromic WH). Nonsyndromic WH is known to be inherited as either an autosomal-dominant or recessive trait. In this study, the authors identified 11 consanguineous families of Pakistani origin with the autosomal recessive form, with associated features including sparse and hypopigmented hair shafts. Mutation analysis revealed pathogenic mutations in the LIPH gene in all 11 families.
    Read the PubMed abstract

    To read more about "Woolly hair"

    J Invest Dermatol ; 622-628 ; March 2009
    Primary microcephaly: mutations found in STIL, encoding a pericentriolar and centrosomal protein
    Primary microcephaly (MCPH) is an autosomal-recessive congenital disorder characterised by smaller-than-normal brain size and intellectual deficit. Three different homozygous mutations in the STIL gene, encoding a pericentriolar and centrosomal protein, were identified. This marks the fifth centrosomal protein implicated in primary microcephaly.
    Read the PubMed abstract

    Am J Hum Genet ; 286-290 ; February 2009
    Ectopia lentis: a homozygous mutation in ADAMTSL4 causes the autosomal-recessive isolated form of the disease
    Ectopia lentis is a genetically heterogeneous condition that is characterised by the subluxation of the lens resulting from the disruption of the zonular fibres. Patients with ectopia lentis commonly present with a marked loss in visual acuity in addition to a number of possibly accompanying ocular complications including cataract, myopia, and retinal detachment. The authors here describe an isolated form of ectopia lentis in a large consanguineous family that shows autosomal-recessive inheritance. They found mutations in the ADAMTSL4 gene, a gene that plays a role in the development and/or integrity of the zonular fibres.
    Read the PubMed abstract

    To read more about "Ectopia lentis isolated"

    Am J Hum Genet ; 274-278 ; February 2009
    Cone-rod dystrophy with amelogenesis imperfecta: mutations in CNNM4 at cause
    Cone-rod dystrophy with amelogenesis imperfecta can be found isolated or together in a syndromic form. Two separate studies identify homozygous mutations in the ancient conserved domain protein 4 gene (CNNM4) that either generate a truncated protein or occur in highly conserved regions of the protein. Given that CNNM4 is implicated in metal ion transport, cone-rod dystrophy and amelogenesis imperfecta may originate from abnormal ion homeostasis.
    Read the first PubMed abstract
    Read the second PubMed abstract

    To read more about "Pancreatoblastoma"

    Am J Hum Genet ; 259-265 ; February 2009
    Am J Hum Genet ; 266-273 ; February 2009

    Primary ciliary dyskinesia with central-microtubular-pair abnormalities: two radial spoke head protein gene mutations at cause
    Primary ciliary dyskinesia (PCD) is a genetically heterogeneous inherited disorder arising from dysmotility of motile cilia and sperm. This is associated with a variety of ultrastructural defects of the cilia and sperm axoneme that affect movement, leading to clinical consequences on respiratory-tract mucociliary clearance and lung function, fertility, and left-right body-axis determination. The authors performed whole-genome SNP-based linkage analysis in seven consanguineous families with PCD and central-microtubular-pair abnormalities. Mutations were subsequently identified in two positional candidate genes, RSPH9 and RSPH4A. Haplotype analysis identified a common ancestral founder effect RSPH4A mutation present in UK-Pakistani pedigrees. Both RSPH9 and RSPH4A encode protein components of the axonemal radial spoke head.
    Read the PubMed abstract

    To read more about "Primary ciliary dyskinesia"

    Am J Hum Genet ; 197-209 ; February 2009
    Congenital sodium diarrhea: mutations in SPINT2 at cause in syndromic form
    Autosomal-recessive congenital sodium diarrhea (CSD) is characterised by perinatal onset of a persistent watery diarrhea with nonproportionally high fecal sodium excretion. In this study, SPINT2 mutations were found in syndromic-CSD patients and were associated with loss of protein synthesis or failure to inhibit the serine protease trypsin in vitro. The authors delineate syndromic CSD as a distinct disease entity caused by SPINT2 loss-of-function mutations.
    Read the PubMed abstract

    To read more about "Sodium diarrhea, congenital"

    Am J Hum Genet ; 188-196 ; February 2009
    FG syndrome: a missense mutation in CASK at cause in an Italian family
    First described in 1974, FG syndrome (FGS) is an X-linked multiple congenital anomaly/intellectual deficit disorder, characterised by high clinical variability and genetic heterogeneity. Five loci (FGS1-5) have so far been linked to this phenotype on the X chromosome, but only one gene, MED12, has been identified to date. Mutations in this gene account for a restricted number of FGS patients with a more distinctive phenotype, referred to as the Opitz-Kaveggia phenotype. The authors report a missense mutation in CASK causing FGS phenotype in an Italian family.
    Read the PubMed abstract

    To read more about "FG syndrome"

    Am J Hum Genet ; 162-177 ; February 2009

    Research in Action
    Amyotrophic lateral sclerosis: a review of the latest findings
    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by progressive muscular paralysis reflecting degeneration of motor neurones in the primary motor cortex, corticospinal tracts, brainstem and spinal cord. The January 2009 supplementary issue of the Annals of Neurology contains a series of articles bringing the reader up to date on the pathophysiology, diagnostics, and management of this disease.
    Consult the table of contents

    To read more about "Amyotrophic lateral sclerosis"

    Fundamental Research
    Cerebral cavernous malformations: a two-hit mechanism of biallelic somatic and germline mutations at cause
    Cerebral cavernomas are vascular anomalies of the central nervous system, comprising dilated blood-filled capillaries lacking structural support. Familial cerebral cavernous malformations (CCMs) have been associated with germline mutations in CCM1, CCM2 or CCM3. Two independent studies assert that the difference in lesion burden between familial and sporadic CCM, combined with limited molecular data, suggest that CCM pathogenesis may follow a two-hit molecular mechanism, similar to that seen for tumour suppressor genes. Biallelic germline and somatic mutations were identified in CCM lesions from all three forms of inherited CCMs. Somatic mutations are found only in a subset of the endothelial cells lining the cavernous vessels and not in interstitial lesion cells. These data suggest that CCM lesion genesis requires complete loss of function for one of the CCM genes and provides clear pathogenetic evidence that the endothelial cell is the cell of disease origin.
    Read the first PubMed abstract
    Read the second PubMed abstract

    To read more about "Cerebral cavernous malformations"

    Hum Mol Genet ; 911-918 ; 1 March 2009
    Hum Mol Genet ; 919-930 ; 1 March 2009

    Bardet-Biedl syndrome: transient ciliogenesis involving proteins is a fundamental characteristic of adipogenic differentiation
    Bardet-Biedl syndrome (BBS) is an inherited ciliopathy generally associated with severe obesity for which the underlying mechanism remains hypothetical. In this study, the authors show that while the proliferating preadipocytes or mature adipocytes are nonciliated in culture, a typical primary cilium is present in differentiating preadipocytes. They also show that the BBS10 and BBS12 proteins are located within the basal body of this primary cilium and inhibition of their expression impairs ciliogenesis, activates the glycogen synthase kinase 3 pathway, and induces peroxisome proliferator-activated receptor nuclear accumulation, hence favouring adipogenesis. Adipocytes derived from BBS-patients’ dermal fibroblasts in culture exhibit higher propensity for fat accumulation when compared to controls. This strongly suggests that a peripheral primary dysfunction of adipogenesis participates to the pathogenesis of obesity in BBS.
    Read the PubMed abstract

    To read more about "Bardet-Biedl syndrome"

    Proc Natl Acad Sci USA ; 1820-1825 ; 10 February 2009
    Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations
    Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. Mutations cause ECM dysfunction by combinations of two mechanisms. First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. Second, secretion of mutant protein can disturb crucial ECM interactions, structure and stability. Targeting endoplasmic reticulum stress might offer a new therapeutic strategy. Osteogenesis imperfecta, chondrodysplasia, Ehlers-Danos syndrome and Marfan syndrome are amongst the rare genetic connective tissue disorders considered in this article.
    Read the PubMed abstract

    Nat Rev Genet ; 173-183 ; March 2009
    Clinical Research
    Atrial septal defect: a new predisposition gene detected
    Atrial septal defect (ASD) is an incomplete septation of atria in the human heart causing circulatory problems. No single gene defect causing ASD has yet been identified. Incomplete heart septation similar to ASD was reported in transgenic mice with both inactive alleles of the gene encoding mammalian zinc metalloprotease, a mammalian tolloid-like 1 (tll1). Here, the authors screened 19 ASD patients and 15 healthy age-matched individuals for mutations in the TLL1 gene. In four nonrelated patients, three missense mutations in coding sequence, and one single base change were detected.
    Read the PubMed abstract

    To read more about "Interauricular communication"

    Eur J Hum Genet ; 344-351 ; March 2009
    Prostate cancer: identification of a susceptibility gene associated with risk of both familial and sporadic disease
    Genetic heterogeneity is a difficulty frequently encountered in the search for genes conferring susceptibility to prostate cancer. To circumvent this issue, the authors selected a large prostate cancer pedigree for genome-wide linkage analysis from a population that is genetically homogeneous. Although the functional SNP remains to be identified, considerable circumstantial evidence, provided by in vivo and in vitro studies, supports a role for the ITGA2 gene in tumour development.
    Read the PubMed abstract

    To read more about "Prostate cancer, familial"

    Eur J Hum Genet ; 368-377 ; March 2009
    Erythropoietic protoporphyria: seasonal palmar keratoderma indicates autosomal recessive inheritance
    Erythropoietic protoporphyria (EPP) is an inherited disorder that results from partial deficiency of ferrochelatase (FECH). It is characterised clinically by acute photosensitivity and, in 2% of patients, liver disease. Inheritance is usually autosomal dominant with low penetrance but is recessive in about 4% of families. A cross-sectional study of 223 patients with EPP in the United Kingdom identified six individuals with palmar keratoderma. The authors now show that these and three additional patients, from six families, have an inherited subtype of EPP which is characterised by seasonal palmar keratoderma, relatively low erythrocyte protoporphyrin concentrations, and recessive inheritance. These findings show that palmar keratoderma is a clinical indicator of recessive EPP, identify a phenotype that occurs in 38% of reported families with recessive EPP, and suggest that patients with this phenotype may carry a lower risk of liver disease than other patients with recessive EPP.
    Read the PubMed abstract

    To read more about "Protoporphyria, erythropoietic"

    J Invest Dermatol ; 599-605 ; March 2009
    Progressive supranuclear palsy: clinicopathological concepts and diagnostic challenges
    Progressive supranuclear palsy (PSP) is a clinical syndrome comprising supranuclear palsy, postural instability, and mild dementia. Neuropathologically, PSP is defined by the accumulation of neurofibrillary tangles. Since the first description of PSP in 1963, several distinct clinical syndromes have been described that are associated with PSP; this discovery challenges the traditional clinicopathological definition and complicates diagnosis in the absence of a reliable, disease-specific biomarker. The authors review the emerging nosology in this field and contrast the clinical and pathological characteristics of the different disease subgroups. For patients for whom the diagnosis is unclear, clinicians must continue to describe accurately the clinical picture of each individual, rather than label them with inaccurate diagnostic categories, such as atypical parkinsonism or PSP mimics. In this way, the development of the clinical features can be informative in assigning less common nosological categories that give clues to the underlying pathology and an understanding of the expected clinical course.
    Read the PubMed abstract

    To read more about "Supranuclear palsy, progressive"

    Lancet Neurol ; 270-279 ; March 2009
    Juvenile myelomonocytic leukaemia: correlation of clinical features with mutational status of GM-CSF signalling pathway genes
    Mutations in RAS, NF1, and PTPN11, constituents of the granulocyte-macrophage colony-stimulating factor signalling pathway, have been recognised in patients with juvenile myelomonocytic leukemia (JMML). The authors assessed 71 children with JMML for RAS, NF1, and PTPN11 mutations and evaluated their clinical significance. Patients with PTPN11 mutation were significantly older at diagnosis and had higher foetal haemoglobin levels, both of which have been recognised as poor prognostic factors. As was expected, overall survival was lower for patients with the PTPN11 mutation than for those without. In an analysis of 48 patients who received haematopoietic stem cell transplantation (HSCT), PTPN11 mutations were also associated with poor prognosis for survival. Mutation in PTPN11 was the only unfavourable factor for relapse after HSCT. All patients who died after relapse had PTPN11 mutation.
    Read the PubMed abstract

    To read more about "Leukemia, myelomonocytic, juvenile form"

    Pediatr Res ; Epub ahead of print ; 26 November 2008
    Astrocytomas, oligodendrogliomas and glioblastomas: patients with IDH1 and IDH2 mutations have better outcome
    A recent genomewide mutational analysis of glioblastomas revealed somatic mutations in the gene IDH1 in a fraction of such tumours, most frequently in those known to have evolved from lower-grade gliomas (secondary glioblastomas). In this study, the authors determined that IDH1 and IDH2 mutations occur in a majority of several types of malignant gliomas, including astrocytomas, oligodendrogliomas and glioblastomas. Such tumours with IDH1 or IDH2 mutations had distinctive genetic and clinical characteristics, and patients had a better outcome.
    Read the PubMed abstract

    To read more about "Astrocytoma"
    To read more about "Glioblastoma"
    To read more about "Oligodendroglioma"

    N Engl J Med ; 765-773 ; 19 February 2009
    Therapeutic Approaches
    Barth syndrome: role of calcium-independent phospholipase A2 in the pathogenesis
    Quantitative and qualitative alterations of mitochondrial cardiolipin have been implicated in the pathogenesis of Barth syndrome, an X-linked cardioskeletal myopathy caused by a deficiency in tafazzin, an enzyme in the cardiolipin remodeling pathway. The authors show that tafazzin deficiency in a Drosophila model of Barth syndrome disrupts spermatid individualization and causes male sterility. This phenotype can be genetically suppressed by inactivation of the gene encoding a calcium-independent phospholipase A(2), iPLA2-VIA, which also prevents cardiolipin depletion/monolysocardiolipin accumulation. The authors also show that treatment of Barth syndrome patient lymphoblasts in tissue culture with the iPLA(2) inhibitor, bromoenol lactone, partially restores their cardiolipin homeostasis.
    Read the PubMed abstract

    To read more about "Barth syndrome"

    Proc Natl Acad Sci USA ; 2337-2341 ; 17 February 2009
    Rett syndrome: partial reversal of Rett Syndrome-like symptoms in MeCP2 mutant mice
    Rett Syndrome (RTT) is a severe form of X-linked intellectual deficit caused by mutations in the gene MECP2 coding for methyl CpG-binding protein 2. Mice deficient in MeCP2 have a range of physiological and neurological abnormalities that mimic the human syndrome. Here the authors show that systemic treatment of MeCP2 mutant mice with an active peptide fragment of Insulin-like Growth Factor 1 (IGF-1) extends the life span of the mice, improves locomotor function, ameliorates breathing patterns, and reduces irregularity in heart rate. In addition, treatment with IGF-1 peptide increases brain weight of the mutant mice.
    Read the PubMed abstract

    To read more about "Rett syndrome"

    Proc Natl Acad Sci USA ; 2029-2034 ; 10 February 2009
    Diagnostic Approaches
    Huntington disease: decreasing uptake of predictive testing in a German centre
    In this retrospective study, the authors examined changes in decision-making for and against the predictive genetic test for Huntington disease including 478 persons at risk who had undergone genetic counselling in one centre in Germany between 1993 and 2004. At the outset of the counselling procedure the majority of subjects (71%) wanted to make use of the test, yet the actual demand of the predictive test result declined from 67% to 38% over the years. Further studies are necessary to investigate whether changes of test demand rates are a general phenomenon.
    Read the PubMed abstract

    To read more about "Huntington disease"

    Eur J Hum Genet ; 295-300 ; March 2009
    Chronic lymphocytic leukaemia: B-cell clones as early markers
    In this prospective cohort study, the authors tested the hypothesis that chronic lymphocytic leukemia (CLL) is always preceded by monoclonal B-cell lymphocytosis (MBL). They found that in peripheral blood obtained up to 77 months before a CLL diagnosis, prediagnostic B-cell clones were present in 44 of 45 patients with CLL.
    Read the PubMed abstract

    To read more about "Leukemia, B-cell lymphocytic, chronic"

    N Engl J Med ; 659-667 ; 12 February 2009

    Patient Management and Therapy
    Idiopathic thrombocytopenic purpura: effect of eltrombopag on platelet counts and bleeding during treatment
    Eltrombopag is an oral, non-peptide, thrombopoietin-receptor agonist that stimulates thrombopoiesis, leading to increased platelet production. This study assessed the efficacy, safety, and tolerability of once daily eltrombopag 50 mg, and explored the efficacy of a dose increase to 75 mg in a this phase III, randomised, double-blind, placebo-controlled study of adults from 63 sites in 23 countries with chronic idiopathic thrombocytopenic purpura. Patients receiving eltrombopag had less bleeding at any time during the study than did those receiving placebo. Eltrombopag was found to be an effective treatment for management of thrombocytopenia in chronic idiopathic thrombocytopenic purpura.
    Read the PubMed abstract

    To read more about "Thrombocytopenic purpura, autoimmune"

    Lancet ; 641-648 ; 21 February 2009
    Familial dysautonomia carriers: implications for a new therapeutic strategy targeting mRNA splicing with kinetin
    Familial Dysautonomia (FD) is caused by an intronic splice mutation in the IkappaB kinase associated protein gene (IKBKAP) that leads to partial skipping of exon 20 and tissue-specific reduction of IkappaB kinase associated protein/Elongator protein 1 (IKAP/ELP-1 protein). Kinetin increases IKBKAP mRNA and protein expression in FD cell lines. To determine if oral kinetin alters IKBKAP splicing in vivo, the authors administered kinetin to 29 healthy carriers of the major FD mutation for 8 days. This is the first report of in vivo IKBKAP splicing modification and strongly suggests the therapeutic potential of kinetin in FD and perhaps in other splicing disorders.
    Read the PubMed abstract

    To read more about "Familial dysautonomia"

    Pediatr Res ; Epub ahead of print ; 21 November 2008
    Spinal muscular atrophy types I, II and III: no treatment has shown significant efficacy
    Two free-access Cochrane Library review articles analyse the scientific publications evaluating the medical treatments tested on patients with spinal muscular atrophy types I, II and III. The authors conclude that to date, no treatment has been shown to have significant efficacy.
    Consult the article on Spinal muscular atrophy type I
    Consult the article on Spinal muscular atrophy types II and III

    To read more about "Proximal spinal muscular atrophy, type 1"
    To read more about "Proximal spinal muscular atrophy, type 2"
    To read more about "Proximal spinal muscular atrophy, type 3"

    Small, medium and large vessel vasculitis: EULAR issues recommendations for management
    To develop European League Against Rheumatism (EULAR) recommendations for the management of large vessel vasculitis, an expert group representing 8 European countries and the USA have issued seven recommendations for the management of large vessel vasculitis. Fifteen recommendations were also made for the management of small and medium vessel vasculitis. On the basis of evidence and expert consensus, these management recommendations are commended for use in everyday clinical practice.
    Read the PubMed abstract for large vessel vasculitis recommendations
    Read the PubMed abstract for small and medium vessel vasculitis recommendations

    To read more about "Predominantly large-vessel vasculitis"

    Ann Rheum Dis ; 318-323 ; March 2009
    Ann Rheum Dis ; 310-317 ; March 2009


    Funding opportunities available via the NIH Challenge Grant program for rare disease projects
    Short-term funding opportunities are available for a variety of rare disease-related projects through the NIH Challenge Grant program, part of the American Recovery and Reinvestment Act of 2009.
    For more information


    Courses & Educational Initiatives
    European Society of Human Genetics/Lithuanian Society of Human Genetics courses for laboratory medical geneticists
    Date: 29 May-1 June 2009
    Venue: Vilnius University, Faculty of Medicine, Vilnius, Lithuania

    This course, focusing on translating genomics into clinical practice will consist of three parts: molecular genetics, cytogenetics and biochemical genetics.
    For further information


    What's on Where?
    International Meeting on Familial Lipodystrophies
    Date: 3-4 April 2009
    Venue: Santiago de Compostela, Spain

    Familial lipodystrophies are a group of rare diseases characterised by a loss of adipose tissue. Despite its low prevalence since 2000 an important number of papers have spread light upon its ethiopathogeny and pathophysiology. In this meeting some of the leading European experts in the field will come together to debate relevant questions related to both the clinical and molecular basis of these disorders.
    For further details

    International Society of Neonatal Screening: 6th European Regional Meeting
    Date: 26-28 April 2009
    Venue: Prague, Czech Republic

    Many interesting and relevant topics, such as Rare diseases and neonatal screening: Consensus building on neonatal screening based on the opinion of European Union patient support groups.
    For further details

    Molecular Mechanisms of Neurodegeneration
    Date: 8-10 May 2009
    Venue: Milan, Italy

    Addressing the most important issues involved in protein toxicity in neurons, providing participants with updated information that could be useful to researchers in the field of neurodegenerative disorders.
    For further details

    7th World Congress on Melanoma
    Date: 12-16 May 2009
    Venue: Vienna, Austria

    A joint meeting with the 5th Congress of the European Association of Dermato-Oncology. Clinicians and researchers will focus on the state of the art in prevention, recognition, and treatment of cutaneous neoplasms covering melanoma and non melanoma skin cancer as well as lymphomas and rare skin tumours.
    For further details

    Symposium on Standards of Care for Children with Cancer
    Date: 13 May 2009
    Venue: Warsaw, Poland

    The results and future possible actions will be discussed following a survey of 25 European countries on state regulations concerning standards of care in paediatric oncology. This survey provides evidence of the disparity in European standards of care and highlight the need for greater attention to be paid towards creating standards in paediatric oncology/haematology wards, particularly in EU member states.
    For further details

    22nd Annual Meeting of the European Musculo-Skeletal Oncology Society
    Date: 13-16 May 2009
    Venue: Stuttgart, Gemany

    Including findings and research activities from the Sarcoma Groups of the German Society for Pediatric Oncology and Hematology. Session on rare bone and soft tissue tumours, and on paediatric and adolescent sarcomas.
    For further details

    8th Balkan Meeting on Human Genetics
    Date: 14-17 May 2009
    Venue: Cavtat, Croatia

    "Rare diseases – public policy, research, diagnosis and management" is one of the topics featured in this conference.
    For further details

    Conference on Recent Standards in Diagnosis, Treatment and Medical Care for Some Rare Neuromuscular Diseases
    Date: 21-23 May 2009
    Venue: Kharkiv, Ukraine

    The agenda will include: Spinal muscular atrophy - modern and newest approaches to diagnostics and treatment; Duchenne muscular dystrophy - modern and newest approaches to diagnostics and treatment; other rare neuromuscular pathologies - latest approaches to diagnostics and treatment; management of respiratory system; orthopaedic aspects; organisation of medical service for rare neuromuscular disorders (diagnosis, registering, conducting of clinical trials and research in compliance with principles of GMP); and more.
    For further details

    The Fourth European Molecular Imaging Meeting
    Date: 27-30 May 2009
    Venue: Barcelona, Spain

    By bringing together top European scientists from various disciplines working in the field of molecular imaging, this high-level meeting will foster the coherence of a sustainable European Molecular Imaging Community with the common goal to translate fundamental research discoveries into medical application and health benefit for the European Society.
    For further details

    12th International Congress on Neuronal Ceroid Lipofuscinoses
    Date: 3-6 June 2009
    Venue: Hamburg, Germany

    The aim of this meeting is to facilitate and speed up exchange between expert scientists and physicians, but also to confront young researchers with the challenges of the largest group of degenerative brain diseases in young people.
    For further details

    First International Conference on Hyperphagia
    4-5 June 2009
    Venue: Baltimore, MD, USA

    Hyperphagia is the extreme unsatisfied drive to consume food which is a hallmark characteristic of Prader-Will syndrome and several other disorders, including Alstrom syndrome, WAGR syndrome, Fragile X syndrome and Laurence-Moon-Bardet-Biedl syndrome. This conference seeks to explore commonalties among affected rare diseases and open new doors of collaboration.
    For further details

    10th European Symposium: Prevention of Congenital Anomalies
    Date: 10 June 2009
    Venue: Bilbao, Spain

    Organised by EUROCAT and the Basque Government’s Ministry of Health, the symposium will share experience on the prevention of congenital anomalies and exhibit advances in prevention in different contexts. The main topics include environmental risk, prenatal diagnosis, and genetic counselling.
    For further details

    Porphyrins and Porphyrias 2009
    Date: 14–18 June 2009
    Venue: Stockholm, Sweden

    The scientific program will cover the latest developments in the field of heme-related disorders. The meeting will include plenary sessions, oral presentations and poster presentations. Contributions will be made from basic scientists, molecular biologists, laboratory and clinical academicians, clinical researchers and physicians working in the field of heme metabolism and heme-related disorders. Deadline for abstract submission: 1 March 2009.
    For further details

    EuroGentest Symposium on Quality and Accreditation
    Date: 18-19 June 2009
    Venue: Leuven, Belgium

    Topics include: accreditation according to ISO 15189, accreditation bodies in Europe and the world, External Quality Assessment schemes, IT solutions to support your quality management system, and experiences from people working in an accredited laboratory or preparing for accreditation.
    For further details

    5th International Congress on Shwachman-Diamond Syndrome
    Date: 19-20 June 2009
    Venue: Amsterdam, Netherlands

    The 5th International Congress on Shwachman- Diamond Syndrome provides a unique opportunity for clinicians, researchers, and patient organisation representatives from around the world to meet.
    For further details

    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

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

    Key Topics include challenges in the pharmaceutical treatment of PKU and treatment of paediatric neurotransmitter disorders.
    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: 17-18 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. Abstract deadline: 15 June 2009.
    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. Further information to appear shortly.
    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". Deadline for submission of abstracts: 15 April, 2009.
    For further details

    Rare Diseases II: Hearing and Sight Loss
    Date: 25-30 October 2009
    Venue: Sant Feliu de Guixols, Spain

    Information to follow.
    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

    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


    Press & Publications
    New book on rare diseases presents snapshot of patient experience for 18 diseases
    The release of a new publication The Voice of 12,000 Patients: Experiences and Expectations of Rare Disease Patients on Diagnosis and Care in Europe was timed to coincide with the Second International Rare Disease Day - an event quickly growing in momentum - scheduled to take place on the last day of February each year. Launched at an event hosted by Commissioner for Health, Androulla Vassiliou, in Brussels, this new text summarises the results of two surveys conducted by the European Organisation for Rare Diseases (EURORDIS), to present a study of patients with 18 different disorders. With over 7,000 rare disorders identified to date, affecting more than 25 million Europeans, this book cannot be considered representative of the definitive experience of rare disease patients; rather it presents the perspective of certain patients with specific conditions – and is limited to those who have access to the support and resources offered by patient associations. Judging from an editorial article appearing in the 14 March issue of the Lancet, the key general messages the new publication seeks to impart have been received by members of the medical community. These include the lack patients report in terms of timely diagnostics, suitably coordinated management, treatment, and services. Some patients surveyed also report a lack of sensitivity on the part of medical professionals and a sense of “rejection”. A limitation to the work lies here, with the lack of clear definition for certain indicators, such as the notion of rejection. Though not in the scope of this work, one immediately feels a need to dig deeper - investigating also the perspective of the medical community. What are the reasons for this reported rejection from the viewpoint of health professionals? Do health professionals deem themselves unqualified to treat conditions they have never before encountered or even studied? Further data are needed in order to present a balanced perspective that would contribute to capturing more of the complex facets rare diseases evoke for the various players - patients, general practitioners and medical experts, as well as diagnostic teams, researchers, industry, and policy-makers. All sides must be examined for sound policies to be developed. The Voice of 12,000 Patients presents a contribution to this arduous task.
    The Voice of 12,000 Patients: Experiences and Expectations of Rare Disease Patients on Diagnosis and Care in Europe is freely available online

    A new Spanish-language book gathers current information on Gaucher disease
    Bone involvement in Gaucher disease is the title of a newly published Spanish language book sponsored by CIBERER (the Biomedical Network Research Centre for Rare Diseases) and the Spanish Foundation for the Study and Treatment of Gaucher Disease (FEETEG). Written by a group of nine scientists, this new work provides complete and updated information on many aspects of this rare disorder - not merely bone manifestations. The book was edited by three CIBERER researchers, all of whom are located in the city of Zaragoza - the core location for Gaucher disease research in Spain. The book presentation took place in February with the presence of the three editors, as well as CBERER scientific director Dr. Francesc Palau and the Aragon Government Health representative. In Spain, 321 cases of Gaucher disease have been reported to date and there are some 870 carriers. Written for professionals, this publication is considered an important contribution to the scientific and health body of knowledge and presents an opportunity to improve quality of life for patients. The book is freely available on the CIBERER website.
    Consult the book

    A new novel from a best-selling author explores the topic of a child born with osteogenesis imperfecta
    A best-selling author has chosen the topic of a child born with rare disease osteogenesis imperfecta (OI) for the subject of her latest work of fiction. Handle with Care, Jodi Picoult’s sixteenth novel, describes the various nuances of living with a rare disease, including how the severity of particular disorders can strain the fabric of the family. When mother Charlotte undertakes legal action against her obstetrician for not informing her in time to terminate the pregnancy that her child would be born severely disabled, conflicts erupt on many levels. Author Picoult, who has had two previous works reach number one on the New York Times bestseller list, spent months researching the disorder, including spending time with families of OI children. This latest novel evokes not only the difficulties of the rare disease patient, but the despair of the parents unable to alleviate the suffering of their child, the turmoil that siblings of children with rare disorders can endure, and the conflict unleashed within the family’s patient support group when Charlotte decides to launch her wrongful birth legal action, which forces her to claim that she did not want her daughter to be born, in order to obtain desperately needed money.
    Title: Handle with Care
    Authors: Jodi Picoult
    Publishing: Atria
    ISBN-13: 978-0743296410


    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, Domenica Taruscio, 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), Joerg Schmidtke (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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