7 April 2010 print
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National action league for rare diseases launches in Germany

The German Federal Ministry of Health initiated a national action league for people with rare diseases - Nationales Aktionsbündnis für Menschen mit Seltenen Erkrankungen (NAMSE) - on 8 March in Berlin. The partners - the major institutions and stakeholders of the German health care system - have adopted a common declaration to improve the health situation for people with rare diseases in Germany. The league is based on three main pillars – the Federal Ministry of Health, the Federal Ministry of Education and Research, and the National Alliance of Patient Groups for Rare Diseases. By the declaration all partners of the league support “the initiative for the formation of a National Action League for people with rare diseases” and, importantly, assert that the “Action League for people with rare diseases will help to implement the recommendation of the Council of the European Union in Germany”. The action league will contribute input to the creation of a National Action Plan for Rare Diseases in Germany; the implementation and monitoring of this plan; and the identification and formation of centres of expertise. With the major institutions and stakeholders of the German health system implicated, along with Germany’s national alliance of patient groups for rare diseases (ACHSE), the ongoing dedication of First Lady Eva Luise Köhler, Orphanet Germany, and other key players, the league is expected to “coordinate measures for improving the health situation of people with rare diseases and to initiate pilot projects and other actions in the field”. The institutions and stakeholders will name representatives to a steering committee which is expected to meet for the first time before the summer holiday.
Learn more (in German language)
Visit the website of the Federal Ministry of Education and Research (English and German languages)

National & International Policy Developments
England’s Chief Medical Officer singles out rare diseases in annual report

The position of Chief Medical Officer was established in the United Kingdom over 150 years ago in response to the cholera epidemics ravaging Victorian England. Since its initiation, the Chief Medical Officer has regularly produced an annual report that brings attention to the current health dilemmas and offers strategies for reducing the burden. The current Chief Medical Officer, Sir Liam Donaldson, has just released his final report – he shall step down from the post following 12 years of dedicated service. Over the years Sir Liam has been instrumental in bringing about policy changes that improve the health of Britons in a number of areas. In his final report, he brings to the fore the issue of rare diseases in a section entitled Rare Is Common. In just seven pages, the report presents a comprehensive overview of the rare disease scenario in England, including statistics, individual portraits, and a synopsis of the major elements of concern: prevention, screening, diagnostics, research, quality of life, management, treatment and cost issues. Six key actions are recommended:

  • Strengthen the network of reference centres for rare diseases to enable better coordination of specialist services, including the transition from paediatric to adult services
  • Ensure that adequate numbers of specialists are trained so that future service needs can be met
  • Appoint a National Clinical Director for rare diseases to oversee the development of clear standards and pathways for the treatment and surveillance of rare diseases, with national registers to support service planning and delivery as well as research
  • Strengthen research, including translational research with economic incentives, to develop and market medicines for the ‘orphan diseases’
  • Raise public and professional awareness of this neglected group of diseases
  • Support international collaborative efforts to share information and resources for rare diseases

  • Should these recommendations be taken up, Sir Liam will leave a legacy as Chief Medical Officer on England’s rare disease community.
    Consult the 2009 Annual Report

    It’s contagious – Europe’s rare disease plan momentum spreads to other parts of world
    At the time that various European countries are defining national priorities for their rare disease patients as delineated by the European Council Recommendation on European Action in the field of Rare Diseases, several non-European countries are also getting in on the action. As was reported in the last issue of OrphaNews Europe, China is taking preliminary steps to consider a strategy for its rare disease patients. Now it is Australia’s turn. A draft of a proposal for a national strategy has been open for consultation on the website of the Australian Paediatric Surveillance Unit. The proposal serves as a platform and a framework from which to develop strategies for implementing elements identified by a National Rare Diseases Working Group that are gathered into eight central principles:

  • Raise awareness of the burden of rare diseases on patients, families, health professionals and the community
  • Provide educational resources and networking opportunities for health professionals to allow them to better identify and manage rare diseases
  • Improve health care for people with rare diseases through access to diagnostic tests, new drugs and other treatments, improved primary care and specialised services
  • Promote research on rare diseases through advocacy for targeted research funds and development of national and international multidisciplinary research partnerships
  • Increase knowledge of the epidemiology and impact of rare diseases in Australia through research
  • Develop and disseminate information to educate patients, parents, carers and the general public, about rare diseases that is relevant in the Australian context
  • Develop an umbrella organisation to support people affected by any rare disease by linking existing organisations to facilitate the co-ordinated development of integrated peer support networks, contact among families and contact among rare diseases interest groups
  • Advocate to government in partnership with families, for people affected by rare diseases

  • The draft plan proposal outlines the rationale and context for each of these principles and then delineates objectives and specific strategies to meet these objectives. As with many plans under development in European countries, the Australian proposal relies on the French National Plan for Rare Diseases as a model. In November, leading stakeholders from the Australian Paediatric Surveillance Unit and other institutions published the article Call for a National Plan for Rare Diseases in the Journal for Paediatrics and Child Health, outlining the benefits of such a plan in Australia.

    US agencies collaborate to speed up innovative drug development
    In the United States, the Food and Drug Administration (FDA) and the National Institutes of Health (NIH) have embarked upon an initiative that will accelerate the journey of bringing innovative medicinal products to market. The new collaboration twines translational research with regulatory science - both key to transforming “biomedical discoveries into products that benefit people”. A Joint NIH-FDA Leadership Council will oversee the initiative to “help ensure that regulatory considerations form an integral component of biomedical research planning and that the latest science is integrated into the regulatory review process”. A Request for Applications that will make $USD 6.75 million available over three years will be issued. A press release states that the “research supported through this initiative should add to the scientific knowledge base by providing new methods, models or technologies that will inform the scientific and regulatory community about better approaches to evaluating safety and efficacy in medical product development”. Orphan drugs represent some 20% of all innovative products.

    US advisory committee recommends adding SCID to newborn screening programme

    In the USA, the Advisory Committee on Heritable Disorders in Newborns and Children has added Severe Combined Immunodeficiency (SCID) to the list of 29 other conditions presently recommended for newborn screening. The Committee is charged with making recommendations to the US Secretary of the Department of Health and Human Services in areas relevant to heritable conditions in newborns and children. SCID is the first condition to be added to the list since 2005. In a letter to the US Secretary of the Department of Health and Human Services, the Committee explains that “because SCID and related T-cell lymphocyte deficiencies are rare in the States, and in order to gain the knowledge necessary through an iterative implemental development of infrastructure needed for ongoing research, evaluation, surveillance, education, and training for screening for SCID and related T-cell lymphocyte deficiencies, the Committee therefore recommends …the addition of SCID to the uniform panel, and related T-cell lymphocyte deficiencies to the list of secondary targets as a comprehensive entity… the National Institutes of Health shall fund surveillance activities to determine health outcomes of affected newborns with any T-cell lymphocyte deficiency receiving treatment as a result of prospective newborn screening; the Health Resources and Services Administration shall fund the development of appropriate education and training materials for families and public health and health care professionals relevant to the screening and treatment of SCID and related T-cell lymphocyte deficiencies". Consult the letter

    Other European news
    Spain launches first paediatric tissue bank in Europe
    In late 2009, the Sant Joan de Déu hospital and the Hospital Clinic (both of Barcelona) became the first in Europe to establish a biobank specifically for paediatric tissue. The entity seeks to promote the donation of much needed paediatric tissue, such as tendons, bones, skin, cornea, and heart and lung valves. While organ donations for transplant in the paediatric population are more frequent, tissue donations are lacking. Such tissues can be vital to rare disease patients. For example, skin tissue can be used for treating children with epidermolysis bullosa. Working with the Transplant Service Foundation, the new bank will network with other banks and institutions in Spain and other parts of Europe. According to a news report, the bank has already been authorised to send tissue to the UK’s National Health Service.
    Research project seeks data on the research use of paediatric biological samples and data
    An ongoing project supported by Italian Clinical and Research Institute Eugenio Medea, which promotes medical and research assistance for children with neurological, psychological and psychiatric diseases and disabilities, is seeking to develop European level policy/practice guidelines on the technical, legal, ethical and societal issues relating to the research use of biological samples and data recruited from children. As a part of this effort, a qualitative-based questionnaire is being distributed that aims to collect data from researchers on practices performed in daily biobanking and research use and also asks for proposals on how to address emerging common issues. Once the questionnaires have been returned and analysed, the project leaders plan to organise a workshop in order to discuss the development of a harmonised policy on the collection, storage, distribution and research use of biomaterials and data from children. The deadline for completing and returning the questionnaire is 15 June 2010. Complete the questionnaire
    Hungary examines its opportunities for rare disease centres of excellence
    A seminar was organised at the Semmelweis University in Budapest late last year to consider how Hungary can develop, organise and operate centres of excellence for rare diseases. Organised by the Hungarian Rare Disease Centre of the National Centre for Healthcare Audit and Inspection, the day-long event gathered genetics experts, patient representatives, health economists and other actors to consider issues such as the role of patient groups, diagnostics and screening for rare diseases, management and care, and reimbursement. Particular emphasis was placed on the notion of collaboration – an essential element for smaller countries with limited health budgets and resources.
    Other International News
    African Society for Immunodeficiencies offers training to health professionals from Western Africa

    In December 2009, the African Society for Immunodeficiencies (ASID) organised a training session for health professionals from Western Africa. Over 120 participants from Benin, Burkina Faso, Guinea, Mali, Morocco, Niger, Senegal, Togo, and Tunisia attended the event, which explored the characteristics, diagnostics, and treatment approaches of the primary immunodeficiency disorders.

    Enormous effort under way in the USA to identify genetic factors in paediatric cancers

    In the USA, St. Jude Children’s Research Hospital and Washington University School of Medicine (St. Louis) are working together to decode the genomes of over 600 paediatric cancer patients. The estimated $US 65 million three-year project seeks to unravel the genetic origins of cancer in children. St. Jude has a substantial biological samples bank that will help serve to further understanding. A press release explains that “Researchers involved in the project also will investigate how paediatric cancer is influenced by variations in the genome, including epigenetic changes, which alter the expression of genes but not the genes themselves. They also will use DNA sequencing data to identify genetic markers that can help physicians decide the best treatment options for cancer patients, based on the genetic profile of their tumours”. The findings from the project are to be made publicly available. All of the paediatric cancers are rare.
    Learn more


    Orphanet News
    Orphanet Journal of Rare Diseases SNIPS its way to the top

    The Orphanet Journal of Rare Diseases (OJRD) has broken yet another barrier in its climb to success. This time it is a new journal indicator - the Source Normalized Impact per Paper, or SNIP, that has accorded the OJRD a star ranking. Developed by Henk Moed at the Centre for Science and Technology Studies (CWTS) at Leiden University, the SNIP is based on Scopus citation data. In a press release, OJRD was named “BioMed Central’s highest-ranking journal based on the SNIP metric, with a value of 1.31 (the median SNIP for the ~17,000 journals in Scopus is 0.52)”. The ranking places OJRD in the top 4% of all Scopus-listed journals. OJRD was accepted for tracking by Medline just one year after its launch and received its first Impact Factor of 1.30 in 2008. In July 2009, OrphaNews Europe reported that the open-access online review dedicated to rare diseases had doubled its impact factor in the space of one year to 3.14 (see article). The press release distinguishes that “the contrast between these two rankings demonstrates that caution is needed when interpreting citation metrics, as much depends on the algorithm used. The SNIP provides a valuable new means to identify high quality journals in fields which may not in general be highly cited.” In order to better understand SNIPs, one can consider it as “similar to a normalized Impact Factor, which weights citations to adjust for the fact that some fields are more citation-rich than others. The intention is that SNIPs will allow more effective comparison of journals between different fields”. OJRD was also accepted for evaluation by Index Copernicus (a journal indexing, ranking and abstracting site) and in April 2009 received a first evaluation of ICV=19.21. The SNIP ranking, along with the rising Medline impact factor, reflect the need for comprehensive, quality information on rare diseases, which can be scarce and difficult to access.

    New Texts
    New Orphanet Journal of Rare Diseases publications
    Rothmund-Thomson syndrome

    New Syndromes
    New Xq27.3q28 duplication syndrome with intellectual deficit, short stature, hypogonadism and facial dysmorphism
    The authors report a new X-linked intellectual deficit syndrome characterised by short stature, hypogonadism and facial dysmorphism, and show that this syndrome is caused by a small Xq27.3q28 interstitial duplication encompassing the FMR1 gene. This family broadens the phenotypic spectrum of FMR1 anomalies in an unexpected manner and the authors suggest that this condition may represent the fragile X syndrome "contre-type".
    Read the PubMed abstract

    Eur J Hum Genet ; 285-290 ; March 2010
    Mutations in PNKP cause microcephaly, seizures and defects in DNA repair
    The authors describe a previously unknown autosomal recessive disease characterised by microcephaly, early-onset, intractable seizures and developmental delay (denoted MCSZ). They identified multiple mutations in PNKP (polynucleotide kinase 3’-phosphatase) that result in severe neurological disease; in contrast, a splicing mutation is associated with more moderate symptoms. Unexpectedly, although the cells of individuals carrying this mutation are sensitive to radiation and other DNA-damaging agents, no such individual has yet developed cancer or immunodeficiency.
    Read the PubMed abstract

    Nat Genet ; 245-249 ; March 2010
    Autosomal dominant and sporadic monocytopenia with susceptibility to mycobacteria, fungi, papillomaviruses, and myelodysplasia
    The authors identified 18 patients with the distinct clinical phenotype of susceptibility to disseminated nontuberculous mycobacterial infections, viral infections, especially with human papillomaviruses, and fungal infections, primarily histoplasmosis, and molds. This syndrome typically had its onset in adulthood and is characterised by profound circulating monocytopenia, B lymphocytopenia, and NK lymphocytopenia. T lymphocytes were variably affected. Ten of these patients developed one or more of the following malignancies: myelodysplasia/leukemia, vulvar carcinoma and metastatic melanoma, cervical carcinoma, Bowen disease of the vulva, and multiple Epstein-Barr virus(+) leiomyosarcoma.
    Read the PubMed abstract

    Blood ; 1519-1529 ; 25 February 2010

    New Genes

    Pheochromocytoma: germline mutations in TMEM127 confer susceptibility
    Pheochromocytomas, catecholamine-secreting tumours of neural crest origin, are frequently hereditary. However, the molecular basis of the majority of these tumours is unknown. The authors identified the transmembrane-encoding gene TMEM127 on chromosome 2q11 as a new pheochromocytoma susceptibility gene. This study identifies TMEM127 as a tumour suppressor gene and validates the power of hereditary tumours to elucidate cancer pathogenesis.
    Read the PubMed abstract

    To read more about "Hereditary pheochromocytoma-paraganglioma syndrome"

    Nat Genet ; 229-233 ; March 2010
    Nephronophthisis-like nephropathy: XPNPEP3 mutations at cause
    The autosomal recessive kidney disease nephronophthisis (NPHP) constitutes the most frequent genetic cause of terminal renal failure in the first three decades of life. Ten causative genes (NPHP1-NPHP9 and (NPHP11), whose products localise to the primary cilia-centrosome complex, support the unifying concept that cystic kidney diseases are "ciliopathies". In two families with an NPHP-like phenotype, the authors detected homozygous frameshift and splice-site mutations, respectively, in the X-prolyl aminopeptidase 3 (XPNPEP3) gene. In contrast to all known NPHP proteins, XPNPEP3 localises to mitochondria of renal cells. However, in vivo analyses also revealed a likely cilia-related function.
    Read the PubMed abstract

    To read more about "Autosomal recessive medullary cystic kidney disease"

    J Clin Invest ; 791-802 ; 1 March 2010
    Neonatal diabetes with subclinical exocrine deficiency: a novel hypomorphic PDX1 mutation responsible
    The authors studied a consanguineous family with two first cousins affected by neonatal diabetes; their four parents had a common ancestor, suggestive of a fully penetrant recessive mutation. They found a novel mutation in the pancreatic and duodenal homeobox 1 gene (PDX1) in the two patients, which segregated with diabetes in the homozygous state. This study broadens the clinical spectrum of PDX1 mutations and justifies screening of this gene in neonatal diabetic patients even in the absence of exocrine pancreas manifestations.
    Read the PubMed abstract

    To read more about "Neonatal diabetes mellitus"

    Diabetes ; 733-740 ; March 2010
    Mody syndrome: differences in clinical presentation, metabolic status, and pathogenic effect
    The authors identify INS gene mutations associated with Maturity-Onset Diabetes of the Young (MODY) or nonautoimmune diabetes in mid-adult life, and explore the molecular mechanisms involved. They describe three INS mutations cosegregating with early-onset diabetes whose clinical presentation is compatible with MODY. These led to the production of (pre)proinsulin molecules with markedly different trafficking properties and effects on ER stress, demonstrating a range of molecular defects in the beta-cell.
    Read the PubMed abstract

    To read more about "MODY syndrome"

    Diabetes ; 653-661 ; March 2010

    Research in Action

    Fundamental Research
    Desmin-regulated lentiviral vectors for skeletal muscle gene transfer
    The authors conducted an extensive quantitative comparison of constitutive and muscle-specific promoter activities in skeletal muscle and nonmuscle systems following lentiviral vectors (LV) delivery in cell lines and neonatal mice. Their data show that LV delivery to hind leg skeletal muscle of neonatal mice results in long-term transgene expression in adulthood. The human desmin (DES) promoter/enhancer is the first muscle-specific control region to match the activity of the highly active constitutive human cytomegalovirus (hCMV) promoter/enhancer in skeletal muscle within a LV context both in vitro and in vivo. DES also confers a more reproducible and tissue-specific transgene expression profile compared to the muscle-specific human muscle creatine kinase (CKM) promoter/enhancer and is therefore a highly attractive regulatory element for use in muscle gene therapy vectors.
    Read the PubMed abstract

    Mol Ther ; 601-608 ; March 2010
    Clinical Research
    Understanding sickle cell carrier status identified through newborn screening
    The expansion of newborn screening (NBS) is increasing the generation of incidental results, notably carrier results. Although carrier status is generally understood to be clinically benign, concerns persist that parents may misunderstand its meaning, with deleterious effects on children and their families. The authors report the results of qualitative interviews with health-care providers, advocates and parents of carrier infants, as well as focus groups with new parents and individuals active with the sickle cell community. Many interpretations of carrier status are in circulation, failing to fit neatly into the categories of "clinically significant" or "benign". This creates challenges for communicating clearly with parents - challenges exacerbated by inconsistent messages from screening programmes regarding the significance of sickle cell carrier status. Disclosure policy related to incidentally generated infant carrier results needs to account for these complex realities.
    Read the PubMed abstract

    To read more about "Sickle cell anemia"

    Eur J Hum Genet ; 303-308 ; March 2010
    Narcolepsy: evidence of autoimmune basis
    Narcolepsy is a sleep disorder characterised by excessive daytime sleepiness and attacks of muscle atonia triggered by strong emotions (cataplexy). Narcolepsy is caused by hypocretin (orexin) deficiency, paralleled by a dramatic loss in hypothalamic hypocretin-producing neurons. It is believed that narcolepsy is an autoimmune disorder, although definitive proof of this, such as the presence of autoantibodies, is still lacking. The authors engineered a transgenic mouse model to identify peptides enriched within hypocretin-producing neurons that could serve as potential autoimmune targets. They identified reactive autoantibodies in human narcolepsy, providing evidence that narcolepsy is an autoimmune disorder.
    Read the PubMed abstract

    To read more about "Narcolepsy-cataplexy"

    J Clin Invest ; 713-719 ; 1 March 2010
    Chromosome 17q12 deletions and duplications: clinical spectrum expands
    Deletions in chromosome 17q12 encompassing the HNF1 beta gene cause cystic renal disease and maturity onset diabetes of the young, and have been recently described as the first recurrent genomic deletion leading to diabetes. The reciprocal duplication of 17q12 is rare and has been hypothesised to be associated with an increased risk of epilepsy and intellectual deficit. The authors conducted a clinical and molecular characterisation of four patients with a deletion and five patients with a reciprocal duplication of this region. The patients with deletion of 17q12 presented with cognitive impairment, cystic renal disease, seizures, and structural abnormalities of the brain. Patients with reciprocal duplications manifest with cognitive impairment and behavioural abnormalities, but not with seizures. These findings expand the phenotypic spectrum associated with rearrangements of 17q12 and show that cognitive impairment is a part of the phenotype of individuals with deletions of 17q12.
    Read the PubMed abstract

    Eur J Hum Genet ; 278-284 ; March 2010
    Turner syndrome: female patients at risk for predominantly male autoimmune diseases
    An increased risk of autoimmune diseases has been observed among women with Turner syndrome. This study was undertaken to investigate whether the autoimmune disease profile in women with Turner syndrome is characterised by diseases with a female or male predominance. Using the Danish Cytogenetic Central Register, the Danish National Patient Register, and the Danish Civil Registration System, the authors estimated relative risk of 46 different autoimmune diseases in a cohort of 798 Danish women with Turner syndrome followed up for 12,461 person-years between 1980 and 2004. They found that women with Turner syndrome are at excess risk of autoimmune diseases, notably autoimmune diseases characterised by male predominance.
    Read the PubMed abstract

    To read more about "Turner syndrome"

    Arthritis Rheum ; 658-666 ; March 2010
    Gene Therapy
    Pompe disease: gel-mediated delivery of AAV1 vectors corrects ventilatory function in mice
    Pompe disease (glycogen storage disease type 2) is a muscular dystrophy that results in respiratory insufficiency. In this study, the authors demonstrate that gel-mediated delivery of recombinant adeno-associated virus serotype 1 vectors can significantly augment ventilatory function at initial and late phases of disease in a mouse model of Pompe disease.
    Read the PubMed abstract

    To read more about "Glycogen storage disease type 2"

    Mol Ther ; 502-510 ; March 2010

    Patient Management and Therapy

    Childhood-onset refractory epilepsy: long-term experience with orphan drug rufinamide
    Recently, the authors published the first post-marketing European experience with rufinamide (RUF) in a retrospective 12-week observational study. This follow-up report summarises the long-term effectiveness and tolerability of RUF after 18 months for the same patient sample. In total, 52 of 60 initially included patients from eight centres in Germany and Austria (45 children and 15 adults aged 1-50 years) with various severe and inadequately controlled epilepsy syndromes continued treatment with RUF after the initial 3-month observation period. The overall response rate after 18 months was 26.7%. The highest response rates were found in the subgroup of patients with Lennox-Gastaut syndrome (35.5%) and in patients with other generalised epilepsy syndromes. A total of 73 adverse events were reported in 37 of 60 patients. The most frequently occurring adverse events were fatigue (18.3%), vomiting (15.0%), and loss of appetite (10.0%). Only 4 new adverse events were reported after week 12. No serious adverse events were observed.
    Read the PubMed abstract

    To read more about "Childhood-onset epilepsy syndrome"

    Epilepsy Behav ; Epub ahead of print ; 23 Feb 2010
    Leber congenital amaurosis: gene therapy safe and effective 1.5 years after administration
    The safety and efficacy of gene therapy for inherited retinal diseases is being tested in humans affected with Leber congenital amaurosis (LCA), an autosomal recessive blinding disease. Three independent studies provided evidence that the subretinal administration of adeno-associated viral (AAV) vectors encoding RPE65 in patients affected with LCA2 due to mutations in the RPE65 gene, is safe and, in some cases, results in efficacy. The authors evaluated the long-term safety and efficacy (global effects on retinal/visual function) resulting from subretinal administration of AAV2-hRPE65v2. Both the safety and the efficacy noted at early timepoints persist through at least 1.5 years after injection in the three LCA2 patients enrolled in the low dose cohort of this trial. A transient rise in neutralizing antibodies to AAV capsid was observed but there was no humoral response to RPE65 protein. The persistence of functional amelioration suggests that AAV-mediated gene transfer to the human retina does not elicit immunological responses which cause significant loss of transduced cells.
    Read the PubMed abstract

    To read more about "Congenital Leber amaurosis"

    Mol Ther ; 643-650 ; March 2010
    Thrombotic thrombocytopenic purpura: survival and relapse
    Survival of patients with thrombotic thrombocytopenic purpura (TTP) improved dramatically with plasma exchange treatment, revealing risk for relapse. The Oklahoma TTP Registry is a population-based inception cohort of all 376 consecutive patients with an initial episode of clinically diagnosed TTP (defined as microangiopathic hemolytic anemia and thrombocytopenia with or without signs and symptoms of ischemic organ dysfunctions) for whom plasma exchange was requested, 1989 to 2008. Survival was not different between the first and second 10-year periods for all patients (68% and 69%) and for patients with idiopathic TTP (83% and 77%). Relapse rate was greater among survivors with ADAMTS13 activity < 10% than among survivors with ADAMTS13 activity of 10% or more. In 41 of 44 survivors, ADAMTS13 deficiency during remission was not clearly related to subsequent relapse.
    Read the PubMed abstract

    To read more about "Thrombotic thrombocytopenic purpura"

    Blood ; 1500-1511 ; 25 February 2010

    Orphan Drugs
    Experts survey the safety regulatory actions taken for orphan drugs approved in Europe and the USA
    A group of experts from the Netherlands undertook an interesting cohort study to determine the nature and frequency of safety-related regulatory measures taken for orphan drug products granted marketing approval in the European Union (EU) and/or the USA between the years 2000 and 2007. Information concerning safety may be more limited for orphan drugs, because of small trial populations, accelerated procedures, the development of innovative ingredients and/or delivery systems, or a combination of factors. Of the 95 orphan products approved during this period in Europe and/or the USA, ten were recipients of safety-regulatory actions. The authors calculate the overall probability of obtaining a first safety-related event is 3.5% after three years and 20.3% after eight years. The study, published in Drug Safety, conclude that “the probability of a first safety-related regulatory action for an orphan drug was slightly lower than that reported in the literature for biologicals in one study and new molecular entities in another study. However, detection of safety issues may be complicated by the limited experience with orphan drugs in practical use due to the low prevalences of the diseases they are used for. Doctors and pharmacists should therefore be vigilant with regard to the occurrence of a safety-related issue for orphan drugs”.
    Consult the PubMed abstract

    FDA approves Carbaglu for N-acetylglutamate synthase deficiency
    The US Food and Drug Administration (FDA) has approved Carbaglu (carglumic acid) for the treatment of N-acetylglutamate synthase (NAGS) deficiency. Carbaglu, developed by Orphan Europe, was given a fast-track designation in the USA in order to treat the rare genetic disease characterised by extremely high plasma levels of ammonia, leading to permanent and irreversible CNS damage. Carbaglu was granted orphan drug status in the US in 1998 and in Europe in 2000. It received EU marketing authorisation in 2003. French non-profit pharmaceutical industry review Prescrire bestowed its sought-after Pilule d’Or (Golden Pill) award to Carbaglu in 2008. Carbaglu permits children afflicted with N-acetylglutamate synthase deficiency to lead a normal life.

    Swiss rare disease grant programme launches second call for projects

    A Swiss grant programme specifically for rare diseases has announced its second call for projects. Independent foundation Gebert Rüf Stiftung is committing CHF2 million (€1.3 million) per year to researchers based at Swiss universities, university hospitals, federal institutes of technology and universities of applied sciences. The Rare Diseases – New Approaches grant programme, which launched last year, is established as a five-year area of activity. The 2009 call selected five finalists from 58 Applications. The chosen topics were: Preventing Nodule Formation in Hyaline Fibromatosis Patients; Genetic Screening for Disease-Causing Mutations in Familial Polycythemia Using Next Generation DNA Sequencing; Gene Hunting for Recessive Hereditary Peripheral Neuropathies by Recent and Highly-Paralell Technologies; Hereditary Sensory Neuropathy Type 1 - Pathomechanism and Therapy; and Identification of New Factors Implicated in Genetic Gonadal Disorders. The application deadline for the second call is 31 July 2010. For more information

    Call for proposals for research on neuronal ceroid lipofuscinoses
    Neuronal ceroid lipofuscinoses (also referred to as Batten disease) are a group of inherited progressive degenerative brain diseases characterised by a decline of mental and other capacities, epilepsy, and vision loss through retinal degeneration, and histopathologically by intracellular accumulation of an autofluorescent material, ceroid lipofuscin, in the neuronal cells in the brain and in the retina. The Batten Disease Support and Research Association (BDSRA) is pleased to announce that limited funds are available to promote research and/or assist in a viable research project/s primarily for, but not limited to, development of novel therapeutic approaches to treatment for NCL, including the identification of bioactive compounds and characterisation of cell-based therapeutic strategies, neuroimaging, proteomic and genomic approaches, and development of treatments that will alleviate the symptoms of Batten disease. Also approaches exploring the neurobiology of NCL disease and determining the molecular pathogenesis in the CNS and further understanding the cell biology of the NCL proteins/enzymes. Proposals will be received for all forms of NCL with emphasis on CLN1, CLN2, and CLN3. This call is open to international participation. The BDSRA is including in its 2010 Request for Proposals the establishment of a new postdoctoral fellowship. Deadline: 15 May 2010.
    For details


    Courses & Educational Initiatives

    23rd Course in Medical Genetics
    Date: 23-28 May 2010
    Venue: EuroMediterranean University Centre of Ronzano, Bologna, Italy

    A week-long postgraduate level course addressed to both researchers and clinicians seeking an up-to-date overview of the field of medical genetics today, providing an overall view of the clinical developments taking place in the major application fields of modern genetics in different medical specialties. The topics covered in the present edition are: Introduction to Medical Genetics and Genome Analysis, Cytogenetics and Clinical Genetics, New Approaches in Medical Genetics, Complex Genetic Disorders and Neurogenetics, Therapy, Technology, Epigenetics and Ethical Issues.
    For further details

    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?

    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.
    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

    4th International Meeting on Congenital Disorders of Glycosylation and Related Disorders
    Date: 22-23 April 2010
    Venue: Leuven, Belgium

    Organised by EUROGLYCANET, a European network for the advancement of research, diagnosis and treatment of a growing group of rare disorders, this meeting will cover all aspects of these disorders, including the discovery of novel types, the study of fundamental aspects of glycosylation, analytical procedures and diagnostic methods and the analysis of models for the disease.
    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

    European Medicines Agency Conference: 10 years of the Orphan Regulation in Europe
    Date: 3-4 May 2010
    Venue: London, UK

    The aim of this conference is to bring together patients, researchers, industry and regulators to discuss and share experiences concerning the development of orphan medicinal products. Plenary sessions, workshops, and discussions will take place.
    For further details

    International Workshop on Consanguinity
    Date: 3-7 May 2010
    Venue: Geneva, Switzerland

    The Department of Genetic Medicine and Development at the University of Geneva in collaboration with ECOGENE21, the International Society of Community Genetics and Genomics, World Health Organization Department of Reproductive Health and Research, and the European Genetics Foundation, is organizing a workshop to increase awareness about the impact of consanguinity on health, to establish basic counselling recommendations on issues involving close kin unions and to promote research into the impact of consanguinity on reproductive behaviour, morbidity, and mortality, with particular focus on the association of consanguinity with non-communicable (complex) disorders and quantitative traits.
    For further details

    EHA-ESH Scientific Workshop: T-cell Acute Lymphoblastic Leukemia Meets Normal T-Cell Development
    Date: 7-9 May 2010
    Venue: Mandelieu, France

    Sessions include genetics, epigenomics, and expression analysis in T-cell acute lymphoblastic leukaemia.
    For further details

    European Medicines Agency Workshop on Stem Cell-Based Therapies
    Date: 10 May 2010
    Venue: London, England

    Bring together regulatory, academic, and industry scientists to share their experiences in the development of stem cell-based cell therapies, within the context of Advanced Therapy Medicinal Products (ATMPs), this workshop will focus on scientific requirements specific to stem cell-based ATMPs. By fostering global dialogue in this innovative field of cell therapy, the EMA intends to stimulate the discussion on the requirements and methods considered acceptable for stem cell-based therapies and to support their development.
    For further details

    3rd Human Variome Project Meeting: Implementation and Integration
    Date: 10-14 May 2010
    Venue: Paris, France

    This third Human Variome Project Meeting will discuss "Implementation and Integration" with the aim of determining how the recommendations and actions from the first meetings can be best implemented in a global collaborative context to prepare the systems necessary to routinely and systematically gather the deluge of variations in genes causing disease. Topics include clinical data collection, genetic data collection, distributed databasing (country and gene specific), country specific collection, key pilot/current projects, central databasing, transfer to central databases, incentives for databasing, ethics of databasing and funding.
    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.
    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

    Fourth Conference on Translational Research in Paediatric Rheumatology
    Date: 27-30 May 2010
    Venue: Genoa, Italy

    “Biological Agents and Emerging Treatments in the Management of Rheumatic Diseases” will address the treatment of both adult and childhood rheumatic diseases with the purpose of reviewing and discussing the progress that has been achieved thus far, the unmet needs that are still faced, and the potential new treatments that the future holds in store. A final session will be devoted to strategies to improve methodologies of translational research on and clinical development in common, as well as rare, forms of rheumatic disorders.
    For further details

    ISDN 2010: 18th Biennial Meeting of the International Society for Developmental Neuroscience
    Date: 6-9 June 2010
    Venue: Estoril, Portugal

    Will feature the most recent advances in fundamental and disease-focused developmental neuroscience. Fragile X, Rett Syndrome, ciliopathy disorders, Meckel-Gruber syndrome are amongst the rare conditions included in the programme.
    For further details

    Giving Patients a Voice: Genetic Interest Group Conference 2010
    Date: 8 June 2010
    Venue: London, England

    The 2010 GIG conference will focus on important developments in patient partnership in healthcare. The afternoon will be dedicated to Rare Disease UK and will be focused on gaining views on how services for patients and families with rare diseases can be improved.
    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. With various satellite symposia available including the one-day event taking place on 11 June entitled "Changing landscape of genetic testing and its impact on clinical and laboratory services and research in Europe".
    For further details

    International Conference on Neuromuscular Diseases: Care and Clinical Trials
    Date: 17–19 June 2010
    Venue: Sao Paulo, Brazil

    This exciting meeting is aimed at healthcare professionals with an interest in neuromuscular disorders (with a special focus on DMD and SMA) and patients and families. Two days of lectures from a strong panel of international and Brazilian speakers will be followed by a dedicated family day with research updates for patients and information on physiotherapy and care.
    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 its treatment.
    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

    17th International Paediatric Colorectal Club Meeting
    Date: 17-19 July 2010
    Venue: Padova, Italy

    Topics include anomalies of the bowel, anorectal malformation, Hirschsprung disease and urological aspects.
    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

    FDA Orphan Drug Workshop
    Date: 3-4 August 2010
    Venue: Minneapolis, Minnesota

    Over two days, FDA staff from the Office of Orphan Products Development (OOPD) will provide regulatory assistance to sponsors to find regulatory paths forward. Most of the time will be spent in application writing and individual one-on-one guidance sessions to develop the strongest possible orphan designation application to be submitted at the close of the workshop.
    For further details

    26th International Congress of Pediatrics
    Date: 4-9 August 2010
    Venue: Johannesburg, South Africa

    Amongst the general programme are symposia on primary immunodeficiency diseases in resource-limited settings, appropriate genetic testing, and a workshop on approaches to the dysmorphic child.
    For further details

    2nd Congress of the European Society for Paediatric Anaesthesiology
    Date: 2-4 September 2010
    Venue: Berlin, Germany

    Amongst the programme of this congress will be a session entitled “Rare diseases: a common problem!” featuring the anaesthetic management of a child with a rare disease; approaches to rare diseases at the national and European level; and the OrphanAnaesthesia project. Deadline for abstract submission: 18 May 2010.
    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 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

    Europlan Conference – How can we support the development of a national strategy for rare diseases in the UK?
    Date: 16 November 2010
    Venue: Manchester, England

    This conference, hosted by the Genetic Interest Group and Rare Disease UK, will discuss ideas and opportunities about how to improve the care, support and information for those living with a rare disease and those who support them. The recommendations developed by the EUROPLAN UK Conference, promoting national strategies and best practices for rare diseases will link with common strategies at a European level.
    For further details


    Press & Publications

    Two new marketing studies focus on orphan drugs
    Two new studies have recently been published that explore the orphan drug scenario. The first, produced by the Tufts University’s Center for the Study of Drug Development is an impact study reporting the trend for orphan designations in the USA. The report describes the number of orphan product designations in the USA, which doubled from 208 in the period between 2000-2002 to 425 in the period of 2006-2008. This report offers an analysis of the American orphan drug market as new technologies emerge. Learn more

    Meanwhile, a study produced by the group Research and Markets entitled Orphan Drugs in Asia 2010: Guidelines and Regulatory Requirements to Help Orphan Drug Products Enter the Asian Market, presents the orphan drug regulations existing throughout Asia and broaches business and financial issues pertaining to orphan drugs in the region. This publication features a list of approved orphan products in the various countries and provides details on various orphan drug associations. Learn more


    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, Raphaël Demonchy, Helen Dolk, Anders Fasth, Laura Fregonese, 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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