3 February 2010 print
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New Genes
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Orphanet overhauls its orphan drugs section to improve and extend accessibility to information

Always striving to improve access to its rich database of information and resources, Orphanet, the European portal for information on rare diseases and orphan drugs, has recalibrated its search engine to render data on Orphan Drugs more accessible from the website’s homepage. In addition to the existing options to search by drug, molecule, or by disease, Orphanet has added four new sub-tabs that improve the visibility of information pertaining to orphan drugs, allowing users to search by a wider range of criteria. The new sub-tabs permit users to view alphabetically the list of all orphan designated products (including each geographical zone for which a substance has been granted a designation). Users can also now obtain an alphabetical list of orphan-designated products with marketing authorisations (also including information on each geographic region in which authorisation has been issued). Alphabetical lists of substances (with related trade name(s) cross-listed), and drug trade names (cross listed with corresponding molecule or active ingredient) are also now available from Orphanet’s homepage. All data pertaining to orphan drugs within the Orphanet database have been extracted from official sources and include all substances which have been granted an orphan designation for disease(s) considered rare in Europe. The database also includes information on products without orphan designation but which have an indication for a rare condition. Furthermore, with the new advanced search options, users may refine their search by sponsor, MA holder and by ATC category.

The results pages have also been redesigned to clearly separate substances from trade names, clarifying that trade names are used solely for products granted marketing authorisation, whereas substances with orphan designation status (prior to marketing authorisation) are referred to by their biochemical substance or molecule. Finally, the orphan designation pages have been enlarged to include information on the sponsor, and the marketing authorisation pages now offer details on the MA holder. These new features are available in the five languages of the Orphanet website.

EU Policy News
Several changes taking place within the European Medicines Agency
As was reported in the 23 December issue of OrphaNews Europe, the European Medicines Agency (EMA) is moving under the wing of the Directorate General for Health and Consumers (DG Sanco) from DG Enterprise as part of a sweep of changes taking place with the next five-year mandate of the European Commission. However, for the EMA, whose Committees for Orphan Medicinal Products (COMP) and Medicinal Products for Human Use (CHMP) are crucial to the rare disease community, the move to DG Sanco is just one of many changes underway.

The EMA has also undergone a significant shift in structure. In a press release issued in December, the EMA describes the re-organisation as encompassing “the integration of human pre- and post-authorisation activities into one unit, to guarantee seamless lifecycle-management of medicines. The creation of a new unit for patient health protection further strengthens the Agency’s focus on safety-monitoring of medicines. In addition, a dedicated group for the management of product data and documentation will improve the efficiency of data management processes throughout the Agency”. Furthermore, the acronym has changed from EMEA to EMA, reflecting the shortening of the agency’s original name, from the "European Medicines Evaluation Agency", which has not been used for several years now, to the "European Medicines Agency". The EMA also got an image make-over, including an updated logo, a new slogan, a new colour chart, new typography and rebranded materials based on these elements. The agency explains that the three words appearing in the new logo represent “the three pillars on which all of the Agency’s work is based: Science, representing the scientific expertise that guides the Agency in all of its regulatory decision-making; Medicines, representing the Agency’s focus on assessing and monitoring medicines to ensure their quality, safety and efficacy; and Health, representing the purpose for which the Agency was created, namely to protect and improve public and animal health”. The EMA’s new identity reflects the increasing emphasis on communication with the public. Indeed, a public website for the EMA is under development and expected to be online in coming months. Readers should take note that the EMA’s overhaul extends to a change of address – electronically, that is. The address for the website has also dropped the second "e" from the acronym to read: http://www.ema.europa.eu/home.htm. Likewise, the email contact address endings within the site have also been updated to read @ema.europa.eu.


National & International Policy Developments
Spain inaugurates first official graduate programme in rare disorders
On 11 January in Seville, the opening ceremony was held for Spain’s first official Master’s programme in rare diseases. The curriculum, coordinated by the Universidad Pablo de Olavide and Universidad Internacional de Andalucía, provides a gradúate-level multidisciplinary overview of the field of rare diseases. The one-year programme offers students theoretical and practical training from national and international experts in the field, including Francesc Palau Martínez (scientific director of the Biomedical Network Research Centre on Rare Diseases CIBERER), Manuel Posada de la Paz (director of Rare Disease Research at the Institute of Health Institute Carlos III), Carmen Ayuso (Clinical Genetics Service, Fundation Jimenez Díaz), Leonardo Salviati (Clinical Genetics Unit, University of Padova), Guillermo Antiñolo Gil (director of Clinical Genetics Unit of Hospital Virgen del Rocio) and Sandra Jackson (Neurologie, Uniklinikum CG Carus, Germany). The course is open to all students with a first degree in the sciences, with priority given to graduates in biotechnology, biology, pharmacology, biochemistry or medicine. For more information
Good news from England: health ministers agree to national commissioning of seven more rare disorders
Health ministers in England have agreed to national commissioning of services, effective 1 April 2010, for patients with the following disorders: neuromyelitis optica; Biedl-Bardet syndrome; Barth syndrome; Xeroderma pigmentosum; type 2 neurofibromatosis; cryopyrin associated periodic syndrome (Muckle Wells disease); and glycogen storage type V disease (McArdle disease). National commissioning establishes national centres of expertise for a specific disease and streamlines funding to one centralised source rather than being scattered amongst different local budgets.

Ethical, Legal & Social Issues

The closing of its Council for Bioethics makes Ireland the sole EU country with no independent body for bioethical issues
The Irish Times in mid-December reported on the pending closure of the Irish Council for Bioethics at the end of 2009. According to the news article, the decision, taken by the Irish Department of Enterprise, Trade and Employment, leaves Ireland as the sole country in the European Union with no independent oversight body for bioethics. In the news article, the Council for Bioethics director expressed concern over, amongst other things, the impact the closing of the Council could have on foreign investment in biomedical research. The decision is attributed to reasons of economy and, according to the news report, has been criticised soundly by experts in the field. There are many aspects of rare disease prevention, diagnostics, and treatments that raise issues pertinent to bioethical consideration. The Irish Council of Bioethics was founded in order to: 1) identify and interpret the ethical questions raised by biomedicine in order to respond to, and anticipate, questions of substantive concern; 2) investigate and report on such questions in the interests of promoting public understanding, informed discussion and education; 3) stimulate discussion through conferences, workshops, lectures, published reports and where appropriate suggest guidelines. OrphaNews Europe has confirmed that funding did cease for the Irish Council for Bioethics on 31 December 2009.

New Syndromes
New syndrome with craniofacial dysmorphism, skeletal anomalies, and intellectual deficit caused by TMCO1 mutation
The authors identified an autosomal recessive condition in 11 individuals in the Old Order Amish of northeastern Ohio. The syndrome was characterised by distinctive craniofacial dysmorphism, skeletal anomalies, and intellectual deficit. The typical craniofacial dysmorphism included brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalised gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represented skeletal anomalies. A homozygous frameshift mutation was identified in the TMCO1 gene. Thus the authors propose "TMCO1 defect syndrome" as the name for this condition.
Read the PubMed abstract

PNAS USA ; 258-263 ; 5 January 2010

New Genes

Charcot-Marie-Tooth disease: autosomal recessive form caused by NEFL mutation
The authors report a homozygous recessive mutation in NEFL, the gene that encodes the light subunit of neurofilaments, in four siblings presenting with a severe form of axonal recessive neuropathy Charcot-Marie-Tooth disease. These results demonstrate for the first time that neurofilaments are required for the maintenance of myelinated peripheral nervous system axons.
Read the PubMed abstract

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

Ann Neurol ; 759-770 ; December 2009
Charcot-Marie-Tooth disease: mutation affecting tRNA synthetase in dominant axonal form
Charcot-Marie-Tooth (CMT) disease is the most common cause of inherited peripheral neuropathy, with an estimated frequency of 1/2500. The authors studied a large family with 17 patients affected by the axonal form of CMT (CMT2) and identified a unique mutation affecting a totally conserved amino acid in the helical domain of cytoplasmic alanyl-tRNA synthetase (AlaRS). A second family with the same mutation and a different founder was then identified in a cohort of 91 CMT2 families. This report broadens the spectrum of defects found in tRNA synthetases. Patients present with sensory-motor distal degeneration secondary to predominant axonal neuropathy, slight demyelination, and no atypical or additional CNS features.
Read the PubMed abstract

To read more about "Autosomal dominant Charcot-Marie-Tooth disease, type 2"

Am J Hum Genet ; 77-82 ; January 2010
Nonsyndromic X-linked sensorineural deafness: loss-of-function mutations in the PRPS1 gene at cause
The authors report a large Chinese family with X-linked postlingual nonsyndromic hearing impairment and identified four different missense mutations in the gene PRPS1 that result in a loss of phosphoribosyl pyrophosphate synthetase 1 activity.
Read the PubMed abstract

To read more about "X-linked nonsyndromic sensorineural deafness, type DFN"

Am J Hum Genet ; 65-71 ; January 2010
Poikiloderma with neutropenia: c16orf57 mutations found
Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia, a rare autosomal-recessive genodermatosis characterised by poikiloderma, pachyonychia, and chronic neutropenia. Mutations in the C16orf57 gene were identified. The unravelled clinical and genetic identity of this condition will allow patients to undergo genetic testing and follow-up.
Read the PubMed abstract

Am J Hum Genet ; 72-76 ; January 2010
Autosomal-dominant striatal degeneration has a mutation in the phosphodiesterase 8B gene
Autosomal-dominant striatal degeneration (ADSD) is an autosomal-dominant movement disorder affecting the striatal part of the basal ganglia. ADSD is characterised by bradykinesia, dysarthria, and muscle rigidity. These symptoms resemble idiopathic Parkinson disease, but tremor is not present. The authors show that ADSD is caused by a complex frameshift mutation in the phosphodiesterase 8B (PDE8B) gene, which results in a loss of enzymatic phosphodiesterase activity. PDE8B is highly expressed in the brain, especially in the putamen, which is affected by ADSD, and degrades cyclic AMP, a second messenger implied in dopamine signalling. Dopamine is one of the main neurotransmitters involved in movement control and is deficient in Parkinson disease.
Read the PubMed abstract

Am J Hum Genet ; 83-87 ; January 2010
Joubert syndrome 2 is associated with a TMEM216 mutation
Patients with Joubert syndrome 2 (JBTS2) suffer from a neurological disease manifested by psychomotor deficit, hypotonia, ataxia, nystagmus, and oculomotor apraxia and variably associated with dysmorphism, as well as retinal and renal involvement. Brain MRI results show cerebellar vermis hypoplasia and additional anomalies of the fourth ventricle, corpus callosum, and occipital cortex. The disease has previously been mapped to the centromeric region of chromosome 11. Using homozygosity mapping in 13 patients from eight Ashkenazi Jewish families, the authors identified a homozygous mutation in the TMEM216 gene in all affected individuals. Thirty individuals heterozygous for the mutation were detected among 2766 anonymous Ashkenazi Jews, indicating a carrier rate of 1:92.
Read the PubMed abstract

To read more about "Joubert syndrome"

Am J Hum Genet ; 93-97 ; January 2010
COACH syndrome has mutations in three genes
COACH syndrome is a rare autosomal recessive disorder characterised by Cerebellar vermis hypoplasia, Oligophrenia (developmental delay/intellectual deficit), Ataxia, Coloboma, and Hepatic fibrosis. The vermis hypoplasia falls in a spectrum of mid-hindbrain malformation called the molar tooth sign (MTS), making COACH a Joubert syndrome related disorder (JSRD). In a cohort of 251 families with JSRD, 26 subjects in 23 families met criteria for COACH syndrome, defined as JSRD plus clinically apparent liver disease. The authors report that mutations in MKS3 are responsible for the majority of COACH syndrome, with minor contributions from CC2D2A and RPGRIP1L.
Read the PubMed abstract

To read more about "COACH syndrome"

J Med Genet ; 8-21 ; January 2010
5q14 microdeletion syndrome: MEF2C mutation is responsible
5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe intellectual deficit with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe intellectual deficit with stereotypic movements, seizures and/or cerebral malformations.
Read the PubMed abstract

J Med Genet ; 22-29 ; January 2010
Focal segmental glomerulosclerosis: mutations in the formin gene INF2 at cause
Focal segmental glomerulosclerosis (FSGS) is a pattern of kidney injury observed either as an idiopathic finding or as a consequence of underlying systemic conditions. Several genes have been identified that, when mutated, lead to inherited FSGS and/or the related nephrotic syndrome. The authors detected nine independent nonconservative missense mutations in INF2, which encodes a member of the formin family of actin-regulating proteins. These mutations, all within the diaphanous inhibitory domain of INF2, segregate with FSGS in 11 unrelated families and alter highly conserved amino acid residues.
Read the PubMed abstract

To read more about "Nephrotic syndrome, idiopathic, steroid-resistant, with focal segmental hyalinosis, familial form"

Nat Gen ; 72-76 ; January 2010
Postaxial acrofacial dysostosis: DHODH mutations identified
The authors identified mutations in the DHODH gene in four patients with postaxial acrofacial dysostosis, a condition also known as Miller syndrome and characterised by mandibular and malar hypoplasia, small and cup-shaped ears, lower lid ectropion, and symmetrical postaxial limb deficiencies with absence of the fifth digital ray and ulnar hypoplasia. DHODH encodes a key enzyme in the pyrimidine de novo biosynthesis pathway.
Read the PubMed abstract

To read more about "Acrofacial dysostosis, postaxial"

Nat Genet ; 30-35 ; January 2010
Noonan syndrome: a restricted spectrum of NRAS mutations at cause
Noonan syndrome, a developmental disorder characterised by congenital heart defects, reduced growth, facial dysmorphism and variable cognitive deficits, is caused by constitutional dysregulation of the RAS-MAPK signalling pathway. Here the authors report that germline NRAS mutations conferring enhanced stimulus-dependent MAPK activation account for some cases of this disorder.
Read the PubMed abstract

To read more about "Noonan syndrome"

Nat Genet ; 27-29 ; January 2010
Amyotrophic lateral sclerosis: chromogranin B P413L variant is a risk factor and modifier of disease onset
Recently, chromogranins were reported to interact specifically with mutant forms of superoxide dismutase that are linked to amyotrophic lateral sclerosis (ALS). This interaction led the authors to analyse the frequencies of sequence variants of the CHGB gene in ALS patients and matched controls from three different countries. Of particular interest was the finding of the P413L CHGB variant present in 10% of ALS patients as compared to 4.5% in controls, conferring a 2.2-fold greater relative risk to develop the disease. Furthermore, the P413L CHGB variant is associated with an earlier age of onset by almost a decade in both sporadic ALS and familial ALS cases. Genetic variation influencing age of onset in ALS had not previously been reported.
Read the PubMed abstract

To read more about "Amyotrophic lateral sclerosis"

PNAS USA ; 21777-21782 ; 22 December 2009

Research in Action

Fundamental Research
Reengineering a receptor footprint of adeno-associated virus enables selective and systemic gene transfer to muscle
Reengineering the receptor footprints of adeno-associated virus (AAV) isolates may yield variants with improved properties for clinical applications. The authors generated a panel of synthetic AAV2 vectors by replacing a hexapeptide sequence in a previously identified heparan sulfate receptor footprint with corresponding residues from other AAV strains. This approach yielded several chimeric capsids displaying systemic tropism after intravenous administration in mice. Of particular interest, an AAV2/AAV8 chimera designated AAV2i8 displayed an altered antigenic profile, readily traversed the blood vasculature, and selectively transduced cardiac and whole-body skeletal muscle tissues with high efficiency. Unlike other AAV serotypes, which are preferentially sequestered in the liver, AAV2i8 showed markedly reduced hepatic tropism.
Read the PubMed abstract

Nat Biotechnol ; 79-82 ; January 2010
Lack of immunotoxicity after regional intravenous delivery of rAAV to nonhuman primate skeletal muscle
In the absence of an immune response from the host, intramuscular (IM) injection of recombinant adeno-associated virus (rAAV) results in the permanent expression of the transgene from mouse to primate models. However, recent gene transfer studies into animal models and humans indicate that the risk of transgene and/or capsid-specific immune responses occurs and depends on multiple factors. Among these factors, the route of delivery is important, although poorly addressed in large animal models. The authors compare the IM and the drug-free regional intravenous (RI) deliveries of rAAV in nonhuman primate skeletal muscle monitoring the host immune response toward the transgene. They show that IM is consistently associated with immunotoxicity and the destruction of the genetically modified myofibers, whereas RI allows the stable expression of the transgene. This has important implications for the design of clinical trials for gene transfer in skeletal muscle.
Read the PubMed abstract

Mol Ther ; 151-160 ; January 2010
Efficient transduction of non-human primate motor neurons after intramuscular delivery of recombinant AAV serotype 6
Retrograde transport of viral vectors in the rodent spinal cord provides a powerful means to administer a therapeutic transgene from the innervated musculature. With the aim of scaling up this approach to non-human primates, the authors injected recombinant adeno-associated vectors (rAAV) serotype 6 expressing enhanced green fluorescent protein (eGFP) into the gastrocnemius muscle of African green monkeys to determine whether this results in efficient transgene delivery to lumbar motor neurons. Cells expressing eGFP were observed across more than 1 cm of the spinal cord 4 weeks after intramuscular injection, reaching more than half of motor neurons in some cross-sections. Furthermore, quantitative PCR on the spinal cord tissue confirmed that eGFP expression within motor neurons was due to bona fide retrograde transport of the vector genome from the muscle. Although infiltrations of macrophages and lymphocytes were observed in the rAAV2/6-injected muscle, there was no detectable immune response within the transduced region of the spinal cord. These findings imply that retrograde delivery of rAAV serotype 6 in a primate species constitutes a non-invasive and robust approach to transduce motor neurons, a crucial target cell population in neurodegenerative disorders, such as amyotrophic lateral sclerosis and spinal muscular atrophy.
Read the PubMed abstract

Gene Ther ; 141-146 ; January 2010
Clinical Research
Hereditary spherocytosis under-recognised in neonates with hyperbilirubinemia
Hereditary spherocytosis (HS) is the most common inherited hemolytic disease among people of Northern European decent. Neonates with HS can develop significant hyperbilirubinemia, but the authors suspect that HS is under-recognised as a cause of neonatal jaundice. In examining records retrospectively, they found seven cases in which HS was present but unrecognised. Follow-up revealed a subsequent diagnosis of HS in 5; the other 2 were no longer in the health system studied. The authors propose that a mean corpuscular hemoglobin concentration of >or=36.0 g/dL can alert caregivers to the possibility of HS.
Read the PubMed abstract

To read more about "Spherocytosis hereditary"

Pediatrics ; 120-125 ; January 2010
Autism and other neuropsychiatric symptoms prevalent in MECP2 duplication syndrome
There have been no objective assessments to determine whether boys with MECP2 duplication have autism or whether female carriers manifest phenotypes. This study characterises the clinical and neuropsychiatric phenotypes of affected boys and carrier females. Eight families (9 males and 9 females) with MECP2 duplication participated. All of the boys demonstrated intellectual deficit and autism. Poor expressive language, gaze avoidance, repetitive behaviours, anxiety, and atypical socialisation were prevalent. Female carriers had psychiatric symptoms, including generalized anxiety, depression, and compulsions that preceded the birth of their children. The majority exhibited features of the broad autism phenotype and had higher nonverbal compared to verbal reasoning skills. Autism is a defining feature of the MECP2 duplication syndrome in boys. Females manifest phenotypes despite 100% skewing of X-inactivation and normal MECP2 RNA levels in peripheral blood.
Read the PubMed abstract

Ann Neurol ; 771-782 ; December 2009
Acute disseminated encephalomyelitis: antigen identified
The authors investigated the occurrence and biological activity of antibodies to native myelin oligodendrocyte glycoprotein (nMOG) in 47 children during a first episode of CNS demyelination (acute disseminated encephalomyelitis n=19 and clinical isolated syndrome n=28). Their findings suggest nMOG as a major target of the humoral immune response in a subgroup of children affected by inflammatory demyelinating diseases of the CNS.
Read the PubMed abstract

To read more about "Encephalitis, acute disseminated"

Ann Neurol ; 833-842 ; December 2009
Gene Therapy
Methylmalonic acidemia: long-term rescue of a lethal murine model via adeno-associated viral gene therapy
Methylmalonic acidemia (MMA) is an organic acidemia caused by deficient activity of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT). This disorder is associated with lethal metabolic instability and carries a poor prognosis for long-term survival. A murine model of MMA that replicates a severe clinical phenotype was used to examine the efficacy of recombinant adeno-associated virus (rAAV) serotype 8 gene therapy as a treatment for MMA. Despite a gradual loss of transgene expression and elevated circulating metabolites in the treated mice, the animals are indistinguishable from unaffected control littermates in size and activity levels. These experiments provide the first definitive evidence that gene therapy will have clinical utility in the treatment of MMA and support the development of gene therapy for other organic acidemias.
Read the PubMed abstract

To read more about "Methylmalonicaciduria, vitamin B12 unresponsive"

Mol Ther ; 11-16 ; January 2010
Leber congenital amaurosis: gene therapy targeting rods and cones rescues retinal degeneration caused by AIPL1 mutations
Aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1) is required for the biosynthesis of photoreceptor phosphodiesterase (PDE). Gene defects in AIPL1 cause a heterogeneous set of conditions ranging from Leber congenital amaurosis, the severest form of early-onset retinal degeneration, to milder forms such as retinitis pigmentosa and cone-rod dystrophy. The authors evaluated whether adeno-associated virus-mediated gene replacement therapy in mice models could restore PDE biosynthesis in rods and cones and thereby improve photoreceptor survival. They validated the efficacy of human AIPL1 (isoform 1) replacement gene controlled by a promoter derived from the human rhodopsin kinase gene, which is active in both rods and cones. They found substantial and long-term rescue of the disease phenotype as a result of transgene expression. This is the first gene therapy study in which both rods and cones were targeted successfully with a single photoreceptor-specific promoter.
Read the PubMed abstract

To read more about "Leber amaurosis, congenital"

Gene Ther ; 117-131 ; January 2010
Duchenne muscular dystrophy: dystrophin via lentiviral vector leads to myogenic progenitor targeting and stable gene expression
The authors generated vectors expressing a functional microdystrophin/enhanced green fluorescence protein fusion (microDys/eGFP) gene. Lentiviral vector injection into neonatal mdx(4cv) muscles resulted in widespread and stable expression of dystrophin for at least 2 years. This expression resulted in a significant amelioration of muscle pathophysiology as assessed by a variety of histological and functional assays. Furthermore, one year after vector injection, up to 20% of the cultured myoblast colonies expressed the microDys/eGFP transgene following myotube formation. Also, transplantation of the muscle mononuclear cells into secondary mdx(4cv) recipients showed their ability to regenerate dystrophin-expressing myofibers in vivo.
Read the PubMed abstract

To read more about "Duchenne and Becker muscular dystrophy"

Mol Ther ; 206-213 ; January 2010
Therapeutic Approaches
Scleroderma: tyrosine kinase inhibitors look promising, but further data is needed
Systemic sclerosis, also referred to as scleroderma, is a fibrosing connective tissue disease with significantly increased mortality. The small molecule tyrosine kinase inhibitor imatinib and related drugs such as dasatinib and nilotinib target simultaneously two of the major profibrotic pathways, TGFbeta- and PDGF- signalling. However, the results of larger controlled trials, currently ongoing, are needed before any conclusions on efficacy and tolerability can be drawn. Until the results of these trials are available, the authors discourage off-label use of Imatinib in single patients.
Read the PubMed abstract

To read more about "Scleroderma"

Ann Rheum Dis ; i48-i51 ; January 2010 Suppl 1
Spinal muscular atrophy: quinazoline derivative improves SMN expression and phenotype in a mouse model
Proximal spinal muscular atrophy (SMA), one of the most common genetic causes of infant death, results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of survival motor neuron (SMN) protein. In humans, the SMN gene is duplicated; SMA results from the loss of SMN1 but SMN2 remains intact. SMA severity is related to the copy number of SMN2. Compounds which increase the expression of SMN2 could, therefore, be potential therapeutics for SMA. Ultrahigh-throughput screening recently identified substituted quinazolines as potent SMN2 inducers. In this study the authors report that the C5-quinazoline derivative D156844 increases SMN expression in neonatal mouse neural tissues, delays motor neuron loss at PND11 and ameliorates the motor phenotype of SMNDelta7 SMA mice.
Read the PubMed abstract

To read more about "Proximal spinal muscular atrophy"

Hum Mol Genet ; 454-467 ; 1 February 2010

Patient Management and Therapy

Birt-Hogg-Dubé syndrome: diagnosis and management
Birt-Hogg-Dubé syndrome (BHD) is an autosomal dominant condition characterised clinically by skin fibrofolliculomas, pulmonary cysts, spontaneous pneumothorax, and renal cancer. The condition is caused by germline mutations in the FLCN gene, which encodes folliculin. The function of this protein is largely unknown, although FLCN has been linked to the mTOR pathway. This review article gives an overview of current diagnosis and management of BHD. The availability of DNA-based diagnosis has allowed insight into the great variation in expression of FLCN, both within and between families. Preventive measures are aimed mainly at early diagnosis and treatment of renal cancer.
Read the PubMed abstract

To read more about "Birt-Hogg-Dube syndrome"

Lancet Oncol ; 1199-1206 ; December 2009
Rendu-Osler-Weber disease: international guidelines for diagnosis and management
Rendu-Osler-Weber disease, also known as hereditary hemorrhagic telangiectasia (HHT), is an autosomal dominant disease with an estimated prevalence of at least 1/5000, and which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. The authors present international guidelines regarding the diagnosis of HHT, the prevention of HHT-related complications, and treatment of symptomatic disease. The Guidelines Working Group included experts (clinical and genetic) from eleven countries who developed 33 recommendations for the diagnosis and management of HHT.
Read the PubMed abstract

To read more about "Rendu-Osler-Weber disease"

J Med Genet ; Epub ahead of print ; 29 June 2009
Juvenile idiopathic arthritis: dynamics of body composition and bone in patients treated with growth hormone
Growth hormone (GH) has a positive impact on growth, bone, and muscle development. The objectives of this study were to demonstrate the effects of GH treatment on regional body composition and bone geometry at final height in 12 patients with juvenile idiopathic arthritis. During GH treatment, there was a significant increase and normalisation of total bone and muscle cross-sectional area (CSA) at final height. In accordance with an anabolic effect of GH, fat mass stabilised at the lower limit of healthy children. At final height, cortical and marrow CSA, relative to total bone CSA, were normalised in GH-treated patients.
Read the PubMed abstract

To read more about "Juvenile Idiopathic Arthritis"

J Clin Endocrinol Metab ; 178-185 ; January 2010
Sarcoidosis: thalidomide improves symptoms of early-onset disease
Early-onset sarcoidosis (EOS), which occurs in children younger than 5 years of age, is associated with granulomatous lesions and a sporadic genetic mutation of the nucleotide-binding oligomerization domain 2 that causes constitutive NF-kappaB activation. The symptoms of EOS can be uncontrollable, progressive, and associated with profound complications. However, appropriate therapy is still under investigation. In this study, thalidomide was given to 2 patients with EOS (a 16-year-old girl and an 8-year-old boy) at an initial dosage of 2 mg/kg/day, and the dosage was increased if necessary. Both patients showed dramatic improvement of their clinical symptoms and laboratory findings. The ability of thalidomide to improve clinical symptoms and laboratory findings in patients with EOS indicates a central role for NF-kappaB activity in this disorder. Inhibition of IKK might be a pharmacologic action by which thalidomide down-regulates NF-kappaB signalling. Thalidomide may be an effective medication in patients with severe complications of EOS, including ocular involvement.
Read the PubMed abstract

To read more about "Early-onset sarcoidosis"

Arthritis Rheum ; 250-257 ; January 2010

Orphan Drugs
Compounded treatments for rare diseases need standardised, validated procedures
A senior pharmacist serving on the National Board for Rare Diseases and in the Pharmacy Department of the University Hospital in Leuven, Belgium, contributes his expertise to OrphaNews Europe on the subject of treatments that are compounded for low prevalence diseases and the need for a harmonised and validated approach:

As early as 1968 the American Society of Hospital Pharmacists identified more than 60 chemical substances used in pharmaceutical compounding that were labeled "not for drug use" (Provost 19681). Some of these ingredients are outdated but many are still marketed worldwide as orphan drugs such as betaine (Cystadane) and sodium phenylbutyrate oral solution (Ammonaps), carglumic acid (Carbaglu) and nitisinone capsules (Orfadin). Nowadays other non-approved chemical ingredients are used in pharmaceutical compounding for the diagnosis, prevention and treatment of life-threatening or chronically debilitating conditions with a very low prevalence. The list mentions 3,4-diaminopyridine (Lambert Eaton myasthenia syndrome), betacarotene (erythropoietic protoporphyria), bi-myconase (sucrase isomaltase deficiency), l-citrulline, diphenylcyclopropenone (alopecia universalis), glycine, hydroxocobalamine (methylmalonacidemia), mepacrine (lupus), primaquine (pneumocystis pneumonia),pyridoxal phosphate (neonatal epilepsia). Most of these ingredients do not have a monograph in a pharmacopoeia and the methods of preparation are not standardised. On the other hand, several approved pharmaceutical ingredients with a pharmacopoeial monograph need to be compounded worldwide for life-saving metabolic rare diseases because a commercial preparation does not exist. For these formulations, experts are calling for an internationally recognised validated procedure. This is the case for: L-arginine oral solution, L-carnitine oral solution, sodium benzoate oral solution and injections, sodium citrate oral solution and injections. Finally, for some commercially available orphan drugs, it could be interesting at this time to publish a compounding procedure, as the 10 year market exclusivity period will soon be finished. Concerned products include: arsenic trioxide injections (acute promyelocytic leukemia), betaine oral solution (homocystinuria), busulfan injections, ibuprofen injections (neonate ductus arteriosus), sodium phenylbutyrate oral solution and capsules (hyperamonemia) and zinc acetate capsules (Wilson disease). Initiatives taken by international societies such as the International Society for Pharmaceutical Compounding (ISPhC) with respect to compounding of orphan drugs would be appreciated by the pharmaceutical corps as well as by patients suffering from a rare disease. The draft of an international compounding formulary for rare diseases would be a useful realisation as the compounded medication would be less expensive for the patient and for the society. The Belgian Federal Drug Agency is working on a Royal Decree that will allow pharmacists to use "not for drug use"-primary ingredients in the compounding for patients with rare diseases under certain conditions.
1Provost G. Homeless or orphan drugs. American Journal of Hospital Pharmacy 1968, 25, 609.

When the orphan drug becomes a blockbuster…
An article appearing in the journal Health Policy examines elements of the United States Orphan Drug Act and recommends reform – all the while warning that the central incentive mechanisms should be left intact. The authors, from neighbouring Canada’s University of British Columbia Department of Medicine, acknowledge that the Orphan Drug Act represents one of the most successful pieces of legislation in recent US history, but assert that certain elements of the Act have “led to commercial and ethical abuses” and thus reform is warranted. The authors cite the “numerous issues which permit specific orphan drugs, under relatively uncommon instances, to become highly profitable and/or treat patient populations in excess of 200,000” and raise issue with some of the 43 products with orphan designation that are considered blockbusters - generating global annual sales of more than one billion US dollars. Acknowledging that proposed legislation in the early 1990s that sought to strip orphan status from products with markets of more than 200,000 patients and/or sales of over US$200,000 had a deleterious effect on orphan drug development, an alternative model taken from Japan is raised, where “pharmaceutical manufacturers are mandated to pay a one-percent sales tax on orphan drugs with annual profits exceeding 100 million yen until government subsidies received by manufacturers have been repaid”. The authors thus recommend the regulation of prices, subsidy paybacks for profitable products, and the creation of an International Orphan Drug Office with regulatory powers.
Consult the PubMed abstract

Rare disease treatment is synonymous with personalised medicine…
An article appearing in the review Translational Research examines the relationship between orphan drug development and personalised medicine. Despite a large collective body of rare disease patients waiting for a treatment, the very rarity of each disease makes the strategy developed between patient and clinician a personalised encounter. The author examines the landscape of orphan drug development, presents his personal experience in developing two products for Wilson disease, a rare inherited disorder characterised by excessive copper accumulation and toxicity, and offers certain recommendations to support academic research and motivate industry that will result in more orphan drugs available for patients in need.
Consult the PubMed abstract


News from the Patients' Associations
On your mark, get set… blog! Transatlantic rare disease stakeholders harness communication tools to discuss pertinent issues

A new tool has joined the arsenal of instruments geared toward raising awareness and discussing the issues pertinent to rare diseases and treatments. Rare Disease Blogs is billed as offering “international opinion on rare diseases and orphan drugs” and is available to the rare disease community and anyone else interested in learning more about the complex issues facing rare disease patients and their caregivers. A transatlantic initiative created jointly by the European Organisation for Rare Disorders (Eurordis) and the USA’s National Organization for Rare Disorders (NORD), the new website has some stellar bloggers onboard – including researchers, policy makers, and patient organisation representatives. The founders hope to increase the involvement of regulators, as well as EMEA patient representative bloggers, in order to enhance the direct exchange of information, experience and opinions within the rare disease community, involving all stakeholders at the international level. Readers are invited to comment on any of the articles, which are divided into two main categories: rare diseases and orphan drugs. Neatly designed and nicely illustrated, the Rare Disease Blogs offer one more way of staying abreast of news in the field.

Network proposes that the rare disease community adopt its own special ribbon made of denim to promote solidarity

The Global Genes Project proposes extending the success that the red AIDS ribbon and pink breast cancer ribbon have brought raising awareness and solidarity to the rare disease community by initiating a jeans (for genes) ribbon. As the campaign slogan states – genes and jeans are “a natural fit - people express themselves in their jeans – but when genes express themselves sometimes they can cause health issues and disease". In a very short time, the Global Genes Project – an initiative of the US-based Children’s Rare Disease Network - reports that it has garnered support from over 100 organisations around the globe – including biotech firms, research institutions, hospitals, and patient organisations coming from Australia, China, Canada, Europe, New Zealand, the Philippines, and the USA. Nicole Boice of the Children’s Rare Disease Network explains the structure of the effort: "We have built a unifying campaign that exists to do a couple of things; 1. create greater public awareness about rare disease; 2. Build a platform that can help educate the public about rare diseases (have partnered with some educators); 3. Be a catalyst for new fundraising programs benefitting individual charities (build broad campaigns that organizations can be involved in without losing their disease identity). This is our community’s ‘pink ribbon’ and I think it is time to give rare disease the attention and resources that they rightly deserve".
Learn more


Courses & Educational Initiatives
Update in Neuromuscular Disorders
Date: 24–27 May 2010
Venue: Clinical Neuroscience Lecture Theatre, National Hospital for Neurology and Neurosurgery, London, UK

This course, now in its third year, is the result of the merging of two popular annual courses with an established international reputation. Amongst the many topics covered are diagnostic approaches in muscular dystrophy; distal myopathies; limb girdle muscular dystrophies; long-term ventilation in DMD; childhood CMT; Pompe disease; congenital myopathies; congenital myasthenia; pharmacological treatment of muscular dystrophies; genetic therapy in DMD; and much more.
For further details

TREAT-NMD Clinical Trials in Neuromuscular Disorders and Other Rare Diseases Workshop
Date: 24-26 June 2010
Venue: The Clinical Trials Coordination Centre, Freiburg, Germany

One of the most common reasons for failed trials is poor protocol design. As neuromuscular disorders are very rare, clinical trials have to be multi-centre or even multinational to include enough patients. As a result, the study design for these trials is usually complex. Also, academic trials have come to face a changed regulatory environment following the implementation of the EU Clinical Trials Directive 2001/20/EC. This TREAT-NMD workshop will explore these issues.
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

Institute of Myology Summer Programme
The Institute of Myology offers the possibility to train in myology via a condensed 10-day course organised in Paris, France. The course is open to foreign students with special attention given to those posted in the French Overseas Territories and those working in developing countries. Many aspects of myology are addressed during the course, from basic science to cutting-edge therapies, and clinical and genetic approaches to muscle diseases, taught via a series of lectures and interactive workshops in English. A certificate of attendance is issued upon completion of the Summer School.
For further details


What's on Where?

2010 Neuromuscular Disorders Conference: Toward a Better Future
Date: 26-27 February 2010
Venue: Sydney, Australia

Featuring a stimulating and progressive programme disseminating the most recent research in the field of neuromuscular conditions, this conference will provide an exciting poster session where up and coming researchers will have an opportunity to present their research to the neuromuscular community.
For further details

3rd International Rare Disease Day
Date: 28 February 2010
Venue: Worldwide

This year’s theme: “Patients and Researchers: Partners for Life!”
For further details

2nd Pan-European Conference on Haemoglobinopathies
Date: 13-14 March 2010
Venue: Berlin, Germany

This conference aims to further strengthen the national and regional support networks for thalassaemia patients in Europe, and increase awareness among European medical professionals and national health authorities of the disorder, its proper management and prevention.
For further details

6th International Conference on Rare Diseases and Orphan Drugs
Date: 18-20 March 2010
Venue: Buenos Aires, Argentina

The 6th International Conference on Rare Diseases and Orphan Drugs (ICORD 2010) for the first time will be convened in the southern hemisphere in agreement with its aim of globalisation of rare disease research and orphan products development activities.
For further details

Health 2.0 Conference
Date: 6-7 April 2010
Venue: Paris, France

The Health 2.0 Conference is the leading showcase of online and mobile technologies in healthcare – including rare disease information and care.
For further details

Sickle Cell: The Next 100 Years
Date: 14-16 April 2010
Venue: Leicester, United Kingdom

Sickle Cell: The Next 100 Years will mark the 100th anniversary since Dr James Herrick published his first observations on ‘peculiar elongated cells’, what is now known as sickle cell disease. This three day conference will bring together a selection of papers offering delegates the chance to explore the social research currently being carried out around the world. Deadline for abstract submission: 15 February 2010.
For further details

ESH-EHA Conference: Innovative Therapies for Red Cell and Iron Related Disorders
Date: 16-18 April 2010
Venue: Cascais, Portugal

Sessions include: Hematopoietic stem cell therapies; molecular switching in erythroid differentiation; gene therapy; iron regulatory pathway for therapies; innovative therapies for red cell disorders, and more.
For further details

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

Topics will include clinical and basic research in the pathophysiology, diagnosis and management of vascular anomalies, as well as the psychosocial challenges faced by the patients.
For further details

Birt-Hogg-Dubé syndrome Symposium 2010
Date: 22 April 2010
Venue: Washington, DC USA

A symposium for reviewing the latest developments for Birt-Hogg-Dubé syndrome.
For further details

XI International Child Neurology Conference
Date: 2-7 May 2010
Venue: Cairo, Egypt

Featuring a rich variety of topics including epilepsy, new anticonvulsants, neurogenetics, CNS infection, nutritional disorders of CNS, demyelinating diseases and leukodystrophies, cerebellar ataxia, advances in spinal muscular atrophy, myasthenia gravis and myasthenic syndromes, neurocutaneous disorders, and much more.
For further details

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

“From policy to effective services for patients”, this conference will look at national plans and strategies for rare diseases, European reference networks and centres of expertise, information and medical education, science from bench to bedside, rare diseases in central and Eastern Europe, and much more. Abstract submission deadline: 28 February 2010
For further details

7th International Prader-Willi Syndrome Conference: East Meets West – A New World for Prader-Willi Syndrome
Date: 20-23 May 2010
Venue: Taipei, Taiwan

A scientific conference bringing together clinicians and researchers from around the world to present and discuss new research findings relevant to the understanding of PWS, new treatments and support strategies, and policy and practice development will be held alongside and combined with a parent and care-provider conference. There is also a young persons’ programme designed especially by the host country.
For further details

22nd Annual Meeting of the European Academy of Childhood Disability
Date: 27-29 May 2010
Venue: Brussels, Belgium
This year’s event - Measures of Progress – Evaluating management outcome in childhood disability - will update and clarify the multidimensional model of disablement specifically applied to management of children with neurodevelopmental disability. Emphasis is on the need for reliable measurement of management outcomes through new findings, from functional imaging to quality of life assessment.
For further details

First International Workshop on Oesophageal Atresia
Date: 27-28 May 2010
Venue: Lille, France

Amongst the topics covered will be: molecular embryology of the foregut; environmental factors in the etiology of esophageal atresia; genetic factors in isolated and syndromic esophageal atresia; ultrasound and MRI prenatal diagnosis of OA: impact on management; Outcomes of esophageal atresia beyond childhood; multidisciplinary clinics: how to improve the follow-up of the patients; and family support groups: an essential contribution to follow-up care.
For further details

European Human Genetics Conference 2010
Date: 12-15 June 2010
Venue: Gothenburg, Sweden

In conjunction with the European Meeting on Psychosocial Aspects of Genetics. Deadline for Abstract Submission: 19 February 2010.
For further details

11th International Symposium on Mucopolysaccharide & Related Diseases
Date: 23-26 June 2010
Venue: Adelaide, South Australia

This year’s theme is "Translating Research into Clinical Reality" with a focus on the areas of newborn screening, prognostics, understanding pathology and therapeutic options.
For further details

6th Alstrom Syndrome Family Conference, Medical Research Clinic and Scientific Symposium
Date: 24-28 June 2010
Venue: Helen, Georgia, USA

Bringing together patients and professionals to further knowledge of Alstrom syndrome and potential treatments.
For further details

International Congress for Tarlov Cysts and Adhesive Arachnoiditis
Date: 2-3 July 2010
Venue: Chambéry, France

International health professionals will discuss recent findings on Tarlov and meningeal cysts, Arachnoïditis, Cauda Equina syndrome, and neuropathic pain. Patients will share their experience. Translations available in English, French and Spanish.
For further details

14th International Conference on Behçet Disease
Date: 8-10 July 2010
Venue: London, England

Presenting new developments in basic and clinical science to bear on the specific issues of Behçet Disease (BD). Topics to be covered will include immunology of BD, vasculitis in BD, genetic basis of BD, regional inflammation and paediatric BD. The programme will also include debates on topics of current interest or controversy.
For further details

2th International Congress on Neuromuscular Diseases
Date: 17-22 July 2010
Venue: Naples, Italy

Offering a variety of sessions including paediatric neuromuscular diseases, genetic testing and diagnosis, pathogenic mechanisms of inherited neuropathies, novel therapeutic targets at the neuromuscular junction, motor neuron diseases, and much more.
For further details

International All Star Vasculitis Symposium
Date: 30 July-1 August 2010
Venue: Long Beach, CA, USA Topics will cover all the vasculitides and will concentrate on the advances in medical treatments, research and quality of life issues for patients.
For further details

MEN 2010: 12th International Workshop on Multiple Endocrine Neoplasia
Date: 16-18 September 2010
Venue: Viareggio, Italy

This two-day meeting will provide a forum for educating basic and clinical investigators on the most recent advances in the area of hereditary endocrine tumours.
For further details

Second AnEUploidy Workshop
Date: 17-19 September 2010
Venue: Split, Croatia

AnEUploidy is the acronym of an Integrated Project (IP) funded by the European Commission within its Sixth Framework Programme. This project aims to contribute to the understanding of the molecular basis and pathogenic mechanisms of aneuploidies. This second workshop will allow colleagues to share views, advancements, and ideas.
For further details

15th International Congress of the World Muscle Society
Date: 12-16 October 2010
Venue: Kumamoto, Japan

The main topics to be addressed include new therapeutic targets for neuromuscular disorders; congenital muscular dystrophies (celebrating the 50th anniversary of Fukuyama congenital muscular dystrophy); and distal myopathies and protein aggregation myopathies.
For further details


Press & Publications

Book from NIH director Francis Collins renders the science of genetics – and personalised medicine - comprehensible to all
The Language of Life: DNA and the Revolution in Personalized Medicine describes the “scientific and medical revolution” that is upon us. So-called personalised medicine has enormous implications in the field of rare diseases, which are largely dominated by genetic causes and/or associations. This new work convinces the general reader what the rare disease patient and their entourage already know – that knowledge can equal power. Knowledge of the causes and mechanisms of a disease eventually leads to prevention, diagnosis, management and (hopefully) treatment. Pioneer gene hunter and director of the National Institutes of Health in the USA, author Dr. Francis Collins explores the many implications of the age of personalised medicine dawning before our eyes.
Title: The Language of Life: DNA and the Revolution in Personalized Medicine
Author: Francis S. Collins
Publisher: Harper (January 5, 2010)
ISBN-10: 0061733172

Rare disease book shortlisted for prestigious prize
A nonfiction account penned by the journalist father of a son diagnosed with cardiofaciocutaneous syndrome has been shortlisted for Canada’s prestigious Charles Taylor prize. The Boy in the Moon: A Father’s Search for His Disabled Son (Random House Canada) recounts the family’s day-to-day life with their seriously affected child who has multiple congenital anomalies as well as intellectual deficit, psychomotor delay, muscular hypotonia, and feeding problems, and eloquently describes the complex and shifting emotions with which the author contends. Competing with three other Canadian nonfiction authors writing on a variety of subjects for the C$25,000 final prize, the final winner will be announced on 8 February.
New Spanish language book: Rare Diseases, Manual of Humanity combines patient and professional views on 26 diseases

A new Spanish-language book Rare diseases, Manual of Humanity was officially released in Madrid last November. The publication contains twenty-six personal stories of people affected with a rare disease, each of whom describe their situation. The experiences are followed by scientific descriptions of the different diseases concerned, written by clinical specialists. Diseases featured include dermatomyositis, interstitial cystitis/painful bladder syndrome, mitochondrial myopathy, epidermolysis bullosa, Prader-Willi syndrome and more. The Spanish Federation of Rare Diseases (FEDER) was involved in the development of the book, together with publishing house Lo Que No Existe. The publication includes two appendices offering general information on rare diseases and listing patient association contacts in Spain. The money raised from book sales will go to FEDER.
ISBN: 978-84-935779-5-7


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, Benjamin Guesdon, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Paloma Tejada, Aurélie Vandeputte
National Contact Point: Till Voigtländer (Austria), Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
For more information on the Rare Diseases Task Force
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