Editorial
International Rare Disease Day calls for a show of solidarity around the world as a record number of countries join hands to raise awareness
It’s hard to believe that five years have already passed since the European alliance of rare disease patient organisations Eurordis launched the very first Rare Disease Day on 29 February – a day that is rare itself - in a bid to raise awareness for the challenges faced by rare disease patients, families, health professionals, researchers, members of industry and government stakeholders.
Here we are again with another 29 February on our calendars and a record number of countries signed up to join in activities devoted to bringing visibility to rare diseases. A very special welcome this year to newcomers Costa Rica, Guatemala, Iceland, Pakistan and Venezuela! Last year’s event included participation from 56 countries, including all EU Member States, Croatia, Russia, Georgia, United States, Canada, Brazil, Japan, China, and Australia and others This year’s event demonstrates that the momentum just keeps growing.
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Amongst the 2012 highlights are the special Rare Disease Day video above available in ten different languages that eloquently puts a face to some of the rare disease names and emphasises that while each rare disease is different, they all share the same challenges in the areas of diagnostics, treatment, care, information and social services, to name a few. Key events taking place around this year’s Rare Disease Day include a symposium in Brussels organised between Eurordis and the European Commission, featuring the presence of the First Lady of Georgia Sandra Roelofs, Ms. Ness Childers (MEP), Paola Testori Coggi (DG Sanco), Ruxandra Draghia Akli (DG Research), Dr. Ségolène Aymé (EUCERD Chair), Mr. Terkel Andersen (Eurordis president), and various EU-funded project leaders all joining together in a day-long event that will showcase the successes achieved over the last decade in the European Union and discuss the way forward.
Rare Disease Day participants are called to a show of hands – literally. At 12:00 GMT, all participants are asked to join and raise hands to demonstrate solidarity with rare disease patients around the world! Whether a dozen people in an office, 100 people at a conference or 1000 people at a public gathering – anyone can participate in this symbolic gesture that will show the world that the community is mobilised for people living with rare diseases and driven by the same objectives. Photos of this demonstration can be sent to the Rare Disease Day website where they will be uploaded and displayed in a Photo Gallery.
Visit the Rare Disease Day website and find an activity taking place near you today. Your participation could make the difference!
EUCERD update
The EUCERD loses a cherished member: Torben Gronnebaek
We fight so very hard, but sometimes we lose. The Rare Disease community lost in a big way with the passing of Torben Gronnebaek. A EUCERD Patient Organisation Representative, Torben Gronnebaek stood on the front line in the battle to improve life for rare disease patients and their families. An active member of Eurordis, founder of the Danish Wilson Association, and President of Rare Disorders Denmark from 1994 to 2009, Torben Gronnebaek, who suffered from Wilson disease, lost his personal battle with lung cancer on 18 February. He was 58 years old. His intelligence and humour will be sorely missed, and his commitment will continue to inspire us. This painful loss only makes us more determined in our efforts to alleviate the suffering rare disease patients and their families face and on this special day for Rare Diseases, we take a quiet moment to remember with gratitude a beloved member of the community.
Defeating the lion: a perspective on solidarity from the EUCERD
Ants can defeat the lion together
-Persian Proverb
The European Union Committee of Experts on Rare Diseases (EUCERD) knows about solidarity. This dedicated group of experts has its own brand of unity – constructed, ironically from a wealth of diversity - the tapestry of talents, cultures, professional experiences and perspectives that enrich and inform each other in the same quest: improving conditions for rare disease patients, their families, caregivers and other stakeholders.
Coming from all 27 European Member States, including Candidate Member Croatia, as well as Switzerland, Norway, and Iceland, the EUCERD members stand shoulder to shoulder in order to combat the shortcomings that plague every aspect of the rare disease challenge - diagnostics, prevention, treatment, social services, knowledge, and training.
At a time when EU harmony is fraying at the edges, the EUCERD remains united in its common cause. The key priority areas identified by the EUCERD for 2012 all further the cause of solidarity, especially the work on building European Reference Networks for rare diseases; the coding and classification activities encompassing the revision of the International Classification of Diseases of the World Health Organization; and updating international nomenclatures using the Orphanet rare disease nomenclature.
As EUCERD Joint Action Coordinator Prof Kate Bushby aptly stated in a recent Lancet Neurology article addressing the topic of European solidarity in the fight against rare diseases: “Future emphasis should be put on sharing resources and expertise”.
The EUCERD and OrphaNews Europe join hands today in solidarity with the rare disease community all over the world.
Test your rare disease knowledge!
For this year's International Rare Disease Day, OrphaNews Europe invites you to take a quick for-fun-only 8 question quiz to see how much you know about the fields of rare diseases and orphan drugs.
Take the quiz
EU Policy News
Commission data protection reform affects medical information too
The European Commission last month proposed a comprehensive reform of the European Union's 1995 Data Protection Directive, seeking to update and modernise the legislation in view of the major technological advances made in recent years. The overhaul also aims to increase harmony between the 27 EU Member States. The revised rules seek to boost the protection of personal information – including certain medical data:
Personal data relating to health should include in particular all data pertaining to the health status of a data subject, information about the registration of the individual for the provision of health services; information about payments or eligibility for healthcare with respect to the individual; a number, symbol or particular assigned to an individual to uniquely identify the individual for health purposes; any information about the individual collected in the course of the provision of health services to the individual; information derived from the testing or examination of a body part or bodily substance, including biological samples; identification of a person as provider of healthcare to the individual; or any information on, for example; a disease, disability, disease risk, medical history, clinical treatment, or the actual physiological or biomedical state of the data subject independent of its source, e.g. from a physician or other health professional, a hospital, a medical device, or an in vitro diagnostic test.
How the revised rules will impact the field of rare disease and orphan drug research, treatment and information, which depends on shared data to combat small and scattered patient populations and lack of resources, will be monitored closely in coming weeks and months by the European Committee of Experts on Rare Diseases and other stakeholders.
Learn more
DG SANCO
New video from the DG Sanco explains how medicinal products are authorised in the EU
Following a visit to the European Medicines Agency (EMA) in London, European Commissioner for Health and Consumer Policy John Dalli and the European Commission have launched a short video, available in 22 European Union languages, which explains to EU citizens the process through which medicinal products are evaluated and authorised for marketing in Europe. The Commission and the EMA share the responsibility of ensuring that medicines authorised in the EU are safe and effective. To date, 62 orphan drugs have received authorisation for marketing by the EMA and many other products are used in the treatment of rare disorders.
To learn more and watch the video
EMA
Confidentiality arrangement with Japan extended another year
The European Medicines Agency and the European Commission have announced the extension of their confidentiality arrangement with the Ministry of Health, Labour and Welfare and the Pharmaceuticals and Medical Devices Agency of Japan, established in 2007, for another year. Under the arrangement, advance drafts of legislation and regulatory guidance documents, scientific advice on medicine development, assessments of applications for marketing authorisations and information concerning the safety of marketed medicines may be exchanged between the two agencies. This is welcome news for the rare disease and orphan drug community, which is striving to reduce duplication of effort and encourage cooperation in the field.
Learn more
European Medicines Agency publishes guideline on use of pharmacogenetics in evaluating pharmacokinetics of medicines
Following a period of public consultation and the consequent adoption by the Committee for Medicinal Products for Human Use, the Guideline on the Use of Pharmacogenetic Methodologies in the Pharmacokinetic Evaluation of Medicinal Products has now been published by the European Medicines Agency. This guideline elaborates requirements and recommendations on when pharmacogenetic studies should be performed; how these studies should be designed and carried out; how the clinical impact of genetic differences between patients should be evaluated; how dosing or treatment recommendations for genetic subpopulations should be studied; consequences for treatment recommendations and labelling; and the impact of interactions between medicines and of impaired or immature organ function. Companies applying for marketing authorisation should follow the guideline from 1 August 2012.
Consult the guidelines
National & International Policy Developments
Other European news
Finland forms national rare disease umbrella group
A new national rare diseases umbrella organisation was founded in Finland last month. It unites rare disease patients, their families and rare disease patient associations in Finland. The new alliance, named HARSO, HArvinainen (rare) Sairauksien (diseases) Organisaatio (organisation) welcomes all Finnish patient organisations that represent one or more rare diseases or disabilities. Harso is run by patients themselves. There were 29 organisations out of a total of 51 in Finland present at the launch of the association which took place on 21 January and featured Terkel Andersen, the president of Eurordis, the European organisation for rare diseases, as guest speaker. The new umbrella group will advocate for the rare disease patients, their families and their organisations in Finland, aiming for the best possible health and social care for the entire rare disease community. One of the main objectives will be to raise awareness of rare diseases and disabilities in order to facilitate diagnosis. Rare diseases and/or disabilities affect the daily lives of approximately 250 000 people in Finland. Harso will provide the rare disease community with strength in numbers for the first time. The organisation unites the rare disease community, creating a common voice and more visibility.
Contact Harso
Other International News
Three articles take stock of the USA’s Undiagnosed Diseases Program
An article appearing in the Journal of the American Medical Association (JAMA) takes stock of the USA National Institutes of Health (NIH) Undiagnosed Diseases Program, an initiative designed to increase the identification of diseases that have eluded diagnosis. Since its launch in 2008, over 6000 cases have been submitted. Of 2000 cases submitted in the first two years, 326 were accepted. Of 160 patients admitted to the NIH Clinical Centre, some 39 diagnoses were made. One new syndrome has been identified: arterial calcification due to deficiency of CD73. More new syndromes detected through the programme are expected to be reported in the scientific literature in coming months. In addition to diagnostics, the programme “… aims to leverage NIH expertise to develop treatment strategies or to enrol participants in research efforts that may help the patients themselves or other affected individuals”.
Consult the PubMed abstract
A second, free-access article further describing the progress of the Undiagnosed Diseases Program appears in Genetics in Medicine and focuses on the insights into rare diseases the programme has afforded. Amongst the intriguing conclusions put forward in this text include the observation that the Undiagnosed Diseases Progam offers insight “… into other aspects of healthcare. First, the remarkable percentage of applications with neurologic problems (43%) emphasizes the need for advances in neurologic diagnostics and therapeutics. Second, regardless of geography, one medical subspecialist had often assumed primary responsibility for complicated patients, leading to a restricted focus on a subset of disease manifestations. Third, the NIH was often the first opportunity for many patients to access a coordinated multidisciplinary evaluation”.
Consult the free-access article
Yet a third article, also open-access, appearing in Disease Models and Mechanisms depicts the how the Undiagnosed Diseases Progam has “…enabled the discovery of several new diseases and disease mechanisms through collaborations between clinical and basic science teams, using the power of both clinical medicine and biological models. … Only a union of clinical and basic researchers – and an awareness of the rich resource that lies in the population of rare disease patients – can achieve this”.
Consult the free-access article
Investigational new drugs for rare diseases: a statement from the Society for Inherited Metabolic Disorders
The Society for Inherited Metabolic Disorders (SIMD) has issued a statement in the journal Molecular Genetics and Metabolism proposing to shift the emphasis for evaluation of new drugs from “…. unattainable and possibly harmful adherence to current standards to a model of best available evidence plus adequate patient informed consent”. Inborn errors of metabolism often require “unique therapeutic interventions arising from the specific biology” underlying a disorder, and could include investigational new drugs, unapproved compounds with “variable levels of previous experience in humans” and off-label use.
Consult the PubMed abstract
Guidance Documents and Recommendations
New guidance available for the mitochondrial syndromes
A freely-available booklet entitled Mitochondrial Medicine, a Clinical Guideline has been created by the Nijmegen Centre for Mitochondrial Disorders in the Netherlands. Addressing both professionals and patients, topics include a description of over a dozen mitochondrial syndromes - all rare conditions - specific detailed information on different aspects of diagnosis, management, prognosis, associated pathologies, and much more. A Mitochondrial Medicine App will be available later this year.
View sample pages of the guideline
Order a copy
Bioinformatics, Registries and Data Management
Assuring quality in institution-based neonatal rare disease prospective inception cohort studies
An article published in Seminars in Fetal & Neonatal Medicine describes the particular issues in designing and operating an institution-based prospective inception cohort study involving neonates with a rare disease. Emphasis is given to the measures for assuring quality and specific factors necessary for a successful outcome include “…a well-developed research infrastructure and effective collaboration among a diverse research team (e.g. investigator, coordinator, data manager, biostatistician), as well as with clinical care personnel”. Qualifying the efforts required for establishment, implementation and quality control as “time- and resource-intensive” with particular “logistical challenges” for rare disease application, the article nonetheless highlights that such studies, particularly when conducted across centres to increase sample size, can “... establish key knowledge on natural history, as well as provide the unique opportunity to identify novel risk factors for disease or prognostic factors for disease outcomes”. Going further, this type of study can “… provide a foundation of highest quality observational evidence to inform the design and execution of [randomized controlled clinical trials] that adopt prognostic stratification of therapeutic interventions in neonatal rare disease”.
Consult the PubMed abstract
Screening and Testing
New on the marketplace: an optimised service for rare disease sequencing and analysis
Oxford Gene Technology (OGT), a provider of innovative clinical genetics and diagnostic solutions to advance molecular medicine, has extended its Genefficiency Sequencing Service to provide a dedicated service for investigating rare diseases. The specifically optimised version of the commercially-available service can help investigators and clinicians identify causative mutations quickly, easily and without the need for in-house technical or bioinformatics expertise. The data produced is of the highest possible quality thanks to OGT’s externally accredited laboratory procedures and quality control systems, while analysis is made easy using the company’s unique rare disease NGS software. The company hopes that the new bespoke, cost-effective service will help speed up research into those diseases that, due to their rarity, have not traditionally attracted extensive research efforts.
Learn more
New report seeks to improve the application of genomic technologies in the UK
The Human Genomics Strategy Group has issued a report highlighting the achievements in genetics research and proposing a “strategic vision to realise the future benefit of genomics” in the UK. The report, which qualifies the increased ability to accurately diagnose rare inherited monogenic diseases as the “most obvious” benefit of the application of genetics to healthcare, makes six key recommendations: Developing a cross-cutting strategic document, to set out the direction on genomic technology adoption in the [National Health Service]; Developing a national central genomic data storage facility; Having the NHS Commissioning Board lead on developing genomic technology adoption; Working to develop a service delivery model for genomic technologies; Having the NHS continue developing genomics education and training; and Raising public awareness of genomic technology and its benefits. These recommendations, if adopted, could help streamline and improve genetic services for rare diseases.
Learn more
Ethical, Legal & Social Issues
A survey of legislation for genetic testing in Western Europe
A review article published in the Journal of Community Genetics examines the legal framework governing the use of genetic tests in the clinical setting in Western Europe. The author notes that five countries have enacted genetic-specific laws, and three have “comprehensive provisions pertaining to genetic testing in their biomedical legislation”. Central provisions cover elements such as informed consent, autonomy and integrity of the person tested, further uses of tests results, and quality requirements for the laboratory and personnel. This article also discusses whole genome sequencing, direct-to-consumer testing and insurance issues.
Consult the PubMed abstract
What is the experience of parents choosing to continue a pregnancy for which a genetic disorder has been detected?
An open-access article appearing in the American Journal of Medical Genetics explores the experience of parents who choose to continue a pregnancy after a genetic disorder has been determined or suspected. The qualitative study sought to understand the extent to which attitudes to disability and prenatal testing impacted on this experience. All of the parents studied reported uncertainty as to what the diagnosis would mean for their child, due to lack of experience of the condition or unknown expression of phenotype. The emotions experienced proved very similar to post-natally diagnosed disorders, although prenatally detected conditions allowed parents increased knowledge and less anxiety following birth and less negative experiences with their child following birth were also reported. A period of ’’self-transcendence’’ following diagnosis was evoked, during which parents were able to more positively reflect on their situation. In addition to support from partners, friends, and family, contact with support groups and other families in the same situation were valued, as well as networks including support groups, physicians and other professionals.
Consult the open-access article
EU Project Follow-up
The evolution of an international registry from an FP7-funded initiative: the International Disorders of Sex Development Registry
Effective research into understanding the aetiology of Disorders of Sex Development (DSDs), as well as long-term outcome of these rare conditions, requires multicentre collaboration across national boundaries and across multiple clinical and research disciplines. The EuroDSD project is one such collaboration involving clinical centres and clinical and genetic experts and which was funded through an FP7 grant between 2008 and 2011. At the heart of the EuroDSD collaboration is a DSD Registry that supports the sharing of clinical data.
The Registry adheres to the highest standards of data governance and security and has attracted much interest internationally, evolving from a European initiative to an international activity. At last review (January 2012) there were 1025 cases added by registered users from 18 centres in 13 countries across 3 continents. A further 25 centres and 10 countries have registered as users (without cases) covering all 6 habitable continents. The age of presentation ranges from https://tethys.nesc.gla.ac.uk/. In case of queries please contact the I-DSD Project Manager, Jillian Bryce.
New Syndromes
A childhood encephalopathy caused by thiamine pyrophosphokinase deficiency
The authors describe five children from three different families presenting with variable degrees of ataxia, psychomotor retardation, progressive dystonia, and lactic acidosis. Investigations showed either compound heterozygous mutations or a homozygous mutation in TPK1 (the gene of the thiamine pyrophosphokinase) in all patients, resulting in decreased TPK protein levels.
Read the PubMed abstract
Ichthyosis, intellectual disability, and spastic quadriplegia due to recessive mutations in ELOVL4
Heterozygous, dominant, mutations in ELOVL4 are known to cause macular degeneration. Here, the authors present two unrelated children, each born to consanguineous parents, with recessive ELOVL4 mutations. They exhibited clinical features of ichthyosis, seizures, intellectual deficit, and spasticity. This constellation resembles Sjögren-Larsson syndrome but presents a more severe neurologic phenotype, and fatty aldehyde dehydrogenase activity is normal.
Read the PubMed abstract
A unique and complex tooth malformation phenotype reveals SMOC2 as an early dental developmental gene
The authors report on a severe developmental dental defect that results in a dentin dysplasia phenotype with major microdontia, oligodontia, and shape abnormalities in a highly consanguineous family. Homozygosity mapping followed by candidate-gene selection identified a homozygous mutation – missed by whole-exome sequencing – in SMOC2 in the two affected children. Further studies in zebrafish confirmed SMOC2 has a role in tooth development.
Read the PubMed abstract
Dysmorphic features, hypogonadotropic hypogonadism, severe microcephaly, and sensorineural hearing loss mapping to 3p21.3
The authors present a new, likely autosomal recessive, pleiotropic disorder seen in four patients (three siblings and their nephew) from a consanguineous family. Hypogonadotropic hypogonadism, severe microcephaly, sensorineural deafness, moderate learning disability, and distinctive facial dysmorphic features characterise the condition. A single, large autozygous region of 13.1Mb on chromosome 3p21 was found common to the affected individuals. The critical region contains 227 protein encoding genes.
Read the PubMed abstract
DAVID: a new association consisting in Deficit in Anterior pituitary function and Variable Immune Deficiency
The authors describe four patients from three unrelated families presenting with ACTH (adrenocorticotropic hormone) deficiency and common variable immunodeficiency (CVID), characterised by defective immunoglobulins production. All patients including two affected siblings had ACTH deficit diagnosed from 5 to 15 years, with symptomatic hypoglycaemia, and CVID diagnosed from 2 to 8 years revealed by recurrent infections. Three of the four patients had a hypoplastic pituitary. One patient had low insulin-like growth factor I and subnormal growth hormone response to stimulation, suggesting that secretion of other pituitary hormones may also be affected. All patients proved negative for pituitary autoantibodies and had no alteration in any of the genes tested (LIF, IKAROS, and EOS).
Read the PubMed abstract
Ketamine-induced biliary dilatation: a new entity linked to drug of abuse
Sixteen reports of ketamine-induced biliary dilatation have been described in the literature, mostly in China where ketamine is a popular drug of abuse. Here, authors from a New York hospital present two cases of ketamine-induced biliary dilatation in young adult Asian patients. This new entity in the United States should be recognised early, as it may prevent unnecessary investigation with blood work, imaging, therapeutic endoscopy, or even surgery.
Read the PubMed abstract
A new X-linked intellectual deficit syndrome
The author studied five generations of a family with eight males suffering from intellectual deficit. The condition also includes microcephaly, micrognathia, osteoarticular and genital anomalies, short stature and other less frequent malformations. Six of these patients were clinically tested using anthropometric indicators and genetically tested using high resolution karyotypes, fragile X research, linkage and MID1 and PQBP1 gene studies. The linkage study mapped the possible causal gene of this syndrome in the Xp11.23-q21.32 segment.
Read the PubMed abstract
New Genes
Neonatal-onset epilepsy, defective mitochondrial energy metabolism, and glycine elevation: homozygous mutation in LIAS identified in a boy
Joubert syndrome and related disorders: identification of mutations in TMEM237
Spondyloepimetaphyseal dysplasia with multiple dislocations: KIF22 is responsible
Familial flecked retinopathy: biallelic mutations found in PLA2G5 in benign form
Congenital aural atresia (microtia): disruption of teashirt zinc finger homeobox 1 (TSHZ1) at cause
Early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD): mutations in MEGF10 are responsible
Paroxysmal kinesigenic dyskinesia, ICCA syndrome, and benign familial infantile seizures: mutations in PRRT2 identified
Brain ; 3490-3498 ; December 2011
J Med Genet ; 76-8; 79-82 ; February 2012
Cell Reports ; 2-12 ; 15 December 2011
Am J Hum Genet ; 152-160 ; 13 January 2012
Autosomal recessive primary microcephaly: the centrosomal gene CEP63 is mutated in a family
Familial digital arthropathy-brachydactyly: TRPV4 mutations reducing channel activity at cause
Frontotemporal dementia with or without motor neuron disease: three research groups report on the pathogenicity of a GGGCC repeat expansion in C9ORF72
Lancet Neurol ; 54-65 ; January 2012
Isolated NADH-CoQ reductase deficiency: defective NDUFA9 is a novel cause of neonatally fatal disease
Split hand - split foot: identification of a DLX5 mutation in a family with autosomal recessive disease
Autosomal recessive progressive external ophthalmoplegia: TK2 (thymidine kinase 2) mutations can underlie the disease
Osteogenesis imperfecta type 3: a mutation causing deficient BMP1 proteolytic activity is responsible in a family with autosomal recessive disease
Kawasaki disease: FCGR2A is a susceptibility locus
Enchondromatosis (Ollier disease) and Maffucci syndrome: somatic mosaic IDH1 and IDH2 mutations are associated
Research in Action
Fundamental Research
Rubinstein-Taybi syndrome: histone acetylation defects, mainly involving H2B and H2A, identified in lymphoblastoid cell lines from patients
Rett syndrome: the two MeCP2 splice variants can substitute for each other and fulfill the basic functions of MeCP2 in the mouse brain
Athabaskan brainstem dysgenesis and Bosley-Salih-Alorainy syndromes: severe cardiovascular malformations in a mouse model (Hoxa1 null mice)
Aneuploid syndromes: induced pluripotent stem cells from patients can model early embryogenesis
Fragile X-associated tremor/ataxia syndrome: activation of gypsy retrotransposon can modulate CGG repeats-mediated neurodegeneration in a drosophila model
Proximal spinal muscular atrophy: severe neuromuscular denervation of clinically relevant muscles, amendable by trichostatin A treatment, in a mouse model
Huntington disease: IRE1 plays an essential role in endoplasmic reticulum stress-mediated aggregation of mutant huntingtin via the inhibition of autophagy flux
Neurofibromatosis type 1: ANRIL is a modifier gene, which influences the number of plexiform neurofibromas
Retinitis pigmentosa: C1q enhances cone photoreceptor survival in a mouse model of autosomal recessive disease
Clinical Research
Graft-versus-host disease: low-dose interleukin-2 can reverse chronic disease
Hereditary nonpolyposis colon cancer: CAPP2 long-term results show that aspirin is an effective chemopreventive agent for colorectal cancer
Advanced neuroendocrine tumours associated with carcinoid syndrome: positive effect of everolimus plus octreotide long-acting repeatable
Renal cell carcinoma: superiority of axitinib over sorafenib as second-line therapy in patients with advanced disease
Glycogen debranching enzyme deficiency: successful experimental treatment of severe cardiomyopathy in an infant
Juvenile idiopathic arthritis: factors associated with treatment response to etanercept
Huntington disease: report of potential endpoints for clinical trials in premanifest and early disease (24 month results of TRACK-HD study)
Meningioma: a meta-analysis of individual paediatric patient data
Myotonic muscular dystrophy types 1 and 2: patients are at increased risk of malignancy
Facioscapulohumeral dystrophy: patients with a phenotype consistent with the disease display genetic and epigenetic heterogeneity
Sirenomelia: an epidemiologic study in a large dataset from the International Clearinghouse of Birth Defects Surveillance and Research
Gene Therapy
Menkes disease: ATP7A gene addition to the choroid plexus results in long-term rescue of the lethal copper transport defect in a mouse model
Huntington disease: progresses towards reduction of huntingtin expression in vitro and in animal models
Neuroblastoma: favourable effects of selective therapeutic targeting of the anaplastic lymphoma kinase with liposomal siRNA in mice
Steinert myotonic dystrophy: stabilisation of expanded CTG repeats in DMPK gene by antisense oligonucleotides
Therapeutic Approaches
Haemophilia: a zymogen-like factor Xa variant corrects the coagulation defect in mouse models
Diagnostic Approaches
Osteogenesis imperfecta: European Molecular Genetics Quality Network (EMQN) guidance for laboratory diagnosis
Huntington disease: discrepancies in reporting the CAG repeat lengths reinforce the need to participate in external quality assessment schemes
Alport syndrome: advances in diagnosis using next-generation sequencing
Patient Management and Therapy
Erdheim-Chester disease: clinical, radiological, prognostic, and therapeutic features
Sickle cell anaemia: a comprehensive review of the literature on children management
Spina bifida: providing a primary care medical home for children and youth
Three new Clinical Utility Gene Cards available
EuroGentest, the EU-funded Network of Excellence for genetic testing, has developed disease-specific points to consider regarding clinical indications for genetic testing - the Clinical Utility Gene Cards (CUGCs). These documents provide clinicians and clinical geneticists with guidance on genetic testing for specific conditions in real settings of clinical genetic services. Published in the European Journal of Human Genetics and also available on the Orphanet website, the CUGCs focus on Mendelian diseases. The European Journal of Human Genetics has published three new Clinical Utility Gene Cards for:
Alveolar rhabdomyosarcoma
Mucopolysaccharidosis type II
Multiple endocrine neoplasia type 2
Orphan Drugs
Political and Scientific News
An assessment of Belgium’s orphan drug reimbursement decision process
A new article assesses with refreshing transparency the system of reimbursement for orphan drugs in Belgium, outlining the official criteria by which reimbursement decisions are achieved: therapeutic value, price, proposed reimbursement tariff, clinical value and budget impact, as well as other negotiable factors including price adjustments, employment incentives for manufacturers, diagnostic test funding by the company, and patient population restrictions. While reimbursement approval is granted to the majority of orphan drugs in the country, the authors identify measures to improve the system, such as good practice principles for analysing budget-impact, further standardisation of applications for reimbursement, and enhanced European cooperation in sharing clinical evidence.
Consult the PubMed abstract
Grants
Two separate funding announcements for Niemann-Pick disease research
To support research and trials into Niemann-Pick Disease Type C an emergency support grant is available providing funds to bridge funding gaps and designed to support the research efforts of existing NPC researchers by preventing the loss of talented and vital staff pending the receipt of other longer term grant funding. Visit the Niemann-Pick Research Foundation website for further details on their research strategy. For further details contact David French or Sue French.
The Ara Parseghian Medical Research Foundation (APMRF) has announced it will be accepting grant requests for the upcoming year for research into Niemann-Pick Disease Type C. Deadline for submission of a letter of intent is 1 March, 2012. For more information
Partnersearch, Job Opportunities
Career opportunity: Inaugural Director of the Center for Orphan Disease Research and Therapy at University of Pennsylvania
The Perelman School of Medicine at the University of Pennsylvania invites applications and nominations for the position of Inaugural Director of the Center for Orphan Disease Research and Therapy. The primary mission of the Center is to expedite the translational science and development of novel therapies for rare and orphan diseases. The Center will achieve this through the promotion of innovative translational research platforms and therapeutic strategies, building on partnerships among investigators, academic institutions, patients and advocacy groups, industry and funding agencies. All interested applicants are invited to send their curriculum vitae and letter of interest to Arthur H. Rubenstein, MBBCh, Search Committee Chair, c/o Margaret M. Lizotte , University of Pennsylvania School of Medicine, 290 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6055.
Learn more
Courses & Educational Initiatives
Tenth European Course on the Evaluation of Medicinal Products in Children
Organized with the European Society for Developmental, Perinatal & Paediatric Pharmacology, and the University Rene Descartes Paris V, and taking place from 21-24 February and 27-30 March 2012, modules for this seminar include: Specific aspects of paediatric pharmacology; Issues relating to trials and drug use in children; Drug development and post-marketing surveillance; Pre/peri-natal drug evaluation and use; Paediatric Investigation Plan design; and more.
For further details
The European School of Genetic Medicine celebrates its 25th anniversary with special courses
The European School of Genetic Medicine will celebrate its 25th anniversary. For the occasion, a renewed edition of the Genetic Counselling Course and a special 25th Anniversary edition of the Medical Genetics Course are being organised. Registration for the upcoming ESGM 2012 Spring Courses is already open, including: Basic and Advanced Course in Genetic Counselling in Practice (14-20 April 2012); Course on Molecular and Statistical Genetics of Consanguinity (13-16 May 2012); 25th Course in Medical Genetics (20-25 May 2012). All ESGM courses can be followed live on the Internet through webcasting.
For further details
OroDysmorphology Course
The first OroDysmorphology course is being held on 24 May 2012 within the context of the 11th Congress of the European Academy of Paediatric Dentistry. Taking place in Strasbourg, France, this pre-congress course will gather European and world experts in the field of syndrome diagnosis and dysmorphology focusing on the oral cavity. The paediatric dentist can contribute to the dysmorphology approach and analysis of a patient/family affected by a syndrome or a rare disease by analysing carefully dental/orofacial malformations, liaising and interacting with the genetic and other health professionals team managing the patient. This hands-on course will allow participants to present and discuss their own cases in front of the expert panel and to benefit from brainstorming and collegial expertise in syndrome and orodental anomalies diagnosis. Therapeutic management of selected cases will be also discussed.
For further details
Goldrain Courses in Clinical Cytogenetics and Prenatal Genetic Diagnosis
The Goldrain Prenatal Genetic Diagnosis course, tentatively scheduled from 6-12 October 2012 at the Goldrain Castle in South Tyrol (Italy), is aimed at both obstetricians and clinical and laboratory geneticists who have strong mutual interests in each other’s field. In order to have the maximum profit from the lectures and exercises, participants should have at least one year of practical experience in prenatal obstetric diagnosis and/or clinical genetics. Besides the lectures, there is room for discussions, student presentations, and at the end a non-compulsory multiple-choice examination. The 2012 Clinical Cytogenetics course has not yet been announced.
For further details
Master of Science in Haemoglobinopathy
A unique opportunity for health professionals to specialise in the field of haemoglobinopathies online with minimum disruption to professional and personal lives. The course has been designed to meet the needs of a wide range of medical professionals, including medical graduates interested in haemoglobinopathy (general physicians, specialists such as paediatricians, haematologists, clinical geneticists, obstetricians/gynaecologists, behavioural scientists); science graduates interested in medical research related to haemoglobinopathy and genetics; and other healthcare professionals interested in haemoglobinopathy – such as counsellors, clinical psychologists, nurse specialists and midwives.
For further details
Orphan Academy 2012 Programme
The Orphan Europe Academy provides healthcare professionals with the opportunity to increase knowledge, develop new ideas and strengthen scientific collaboration by offering training and educational activities for healthcare professionals involved in the diagnosis and management of patients affected by rare diseases.
For further details
EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Workshops
The European network of excellence for all aspects of genetic testing, EuroGentest, under its Quality Management and Accreditation/Certification of Genetic testing Workgroup, has several training workshops available around Europe in coming months that focus on accreditation and quality assurance.
For further details
What's on Where?
Second ASID Congress of the African Society for Immunodeficiencies
Date: 8-11 March 2012
Venue: Hammamet, Tunisia
This second congress – postponed from its original 2011 date - will be an excellent opportunity to strengthen the capacity of colleagues all over the continent to better diagnose and manage patients with PIDs. The commitment and contribution of international experts, societies and associations to this process is highly appreciated.
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European Organisation for Research and Treatment of Cancer (EORTC) 50th Anniversary Conference
Date: 15-16 March 2012
Venue: Brussels, Belgium
The conference offers a unique opportunity to gather all the partners (including national research organizations, health authorities, patient advocacy groups, European Commission, cancer leagues, and the pharmaceutical industry) to celebrate the 50th anniversary of the EORTC network.
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Genomic Disorders 2012
21-24 March 2012
Cambridge, UK
Genomic Disorders 2012 presents an exciting blend of genomic science and clinical medicine. The event aims to bring together scientists and clinicians interested in genomic variation in humans and the mechanisms by which it exerts its phenotypic effects. This year’s meeting will discuss the latest findings relating to the genomic basis of rare disorders, and the role of rare variants in common disease, as these can provide such powerful insights into human biology. Genome wide analyses, including most recently Whole Exome Sequencing, are proving to be of great value in discovering the genetic basis of rare disorders and illustrate the power of humans as a model organism to study. As sequencing technology advances apace, other key aspects of genome science need to develop and grow in parallel.
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The Fourth BHD Symposium for Birt-Hogg-Dubé syndrome
28-30 March 2012
Cincinnati, USA
Addressing topics relating to the understanding, diagnostics and treatment of Birt-Hogg-Dubé syndrome. Programme to be available soon.
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13th International Conference on Neuronal Ceroid Lipofuscinosis and 1st Worldwide Meeting of Batten Disease Int'l Alliance
Date: 28-31 March 2012
Venue: London, England
This is the only forum that brings together those with interests in basic science and clinical care for this group of devastating diseases. A new dimension is added this year by bringing together the newly formed Batten Disease International Alliance (BDIA) for its first worldwide meeting.
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International Symposium on Hepatic Glycogen Storage Diseases
Date: 4-6 April 2012
Venue: Lyon, France
International experts will review the following topics: Glucose metabolism in neonates; A global overview of glycogen metabolism; Liver pathology: steatosis, fibrosis, hepatocellular adenomas and carcinomas and the role of dietary treatment on pathophysiology; Review of kidney, intestinal and muscle complications; and New advances in gene therapy.
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Fourth International Meeting on Primary Central Hypoventilation Syndromes
Date: 13-14 April 2012
Venue: Warsaw, Poland
The fourth international CHS meeting will be organized by the European CHS Consortium and will address physicians, researchers, families and all persons involved or interested in Central Hypoventilation Diseases.
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Myomatrix 2012 Conference
Date: 22-24 April 2012
Venue: Nevada, USA
Myomatrix 2012 is a unique conference dedicated to exploring the junction between muscle and extracellular matrix, the myomatrix, the central starting point of inquiry into underlying disease pathogenesis in the CMDs and muscular dystrophies.
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8th International Congress on Autoimmunity
Date: 9-13 May 2012
Venue: Granada, Spain
Updating physicians, immunologists, rheumatologists, researchers and clinicians interested in autoimmune diseases with the latest available diagnostic tools and new therapeutic avenues. Autoimmunity 2012 provides a key platform for those in search of cures to these diseases, to collaborate, exchange information and to network.
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CILIA 2012 - Cilia in Development and Disease Date: 16-18 May 2012
Venue: London, UK
Sessions will cover: Clinical aspects of ciliopathies and genotype/phenotype prediction; Structure and function of cilia; Role of cilia in development and ciliary signalling modules; Role of cilia in disease – human genetics and animal models; Translational therapy and current and future ciliotherapeutics; and more.
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Sixth International Alkaline Phosphatases Symposium
Date: 16-19 May 2012
Venue: Huningue, France
This upcoming symposium will highlight the wealth of clinical data that has been obtained on the management of hypophosphatasia patients, while also discussing new information about other pathophysiological conditions related to alterations in alkaline phosphatases structure and function.
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6th European Conference on Rare Diseases & Orphan Products
Date: 23-25 May 2012
Venue: Brussels, Belgium
The conference is structured in such a way as to demonstrate the importance of EU actions in the field of rare diseases and review progress to date. With its plenary and parallel sessions addressing specific issues, knowledge-sharing is encouraged, the exchange of real experiences and best practices are integrated into the programme, cooperation and networking are stimulated and awareness is increased while ensuring continuity of action and prevention of duplication of efforts. Less advanced regions in this field will benefit from experience sharing with other areas in Europe. The Opening & Plenary Sessions will be interpreted into six languages: English, French, Spanish, German, Dutch and Russian.
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5th International Conference on Ectodermal Dysplasia (ED2012)
Date: 1-3 June 2012
Venue: Erlanger, Germany
The ectodermal dysplasias are a large, heterogeneous group of hereditary disorders characterized by defective formation of tissues derived from embryonic ectoderm. ED2012 will provide a forum for multidisciplinary discussions on treatment paradigms as well as innovative approaches to improving the lives of patients with ectodermal dysplasia.
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10th International Primary Hyperoxaluria Workshop
Date: 22-23 June 2012
Venue: Bonn, Germany
A venue for exploring advances in the diagnostics, molecular biology, pathophysiology and treatment in the field of hypyeroxaluria.
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European Human Genetics Conference 2012
Date: 23-26 June 2012
Venue: Nurnberg, Germany
A rich programme awaits participants. Symposia include: The molecular basis of facial malformations; Mechanisms and consequences of chromosomal/genetic mosaicism; Primary microcephaly; and much more. Educational sessions include Next-generation sequencing diagnostics; Trinucleotid repeat disorders and more. Plenary sessions include: Targeted pharmacological therapies in genetic disorders (with presentations on Marfan, tuberous sclerosis complex and fragile X); and more.
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European Working Group on Gaucher Disease Meeting
Date: 28-30 June 2012
Venue: Paris, France
The quality of the scientific content at the EWGGD meetings attracts an increasing number of participants with each edition. Participants are recognized experts in their fields, committed to both clinical and basic science in Gaucher disease. New results from basic science, clinical trials and registries will be announced during the meeting. Updated guidelines for the management of Gaucher disease will be released, taking into account the experience of different teams in various countries. A practical session and workshop, dedicated to nurses and paramedics with the objective of better integrating their crucial role in patient management through medical education, based on new practices such as home therapy, will be held.
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World Federation of Hemophilia World Congress
Date: 8-12 July 2012
Venue: Paris, France
The WFH World Congress is the single largest event in the WFH calendar, and is very important to the global bleeding disorders community. Every second year doctors, scientists, healthcare workers, people with bleeding disorders and haemophilia organisations gather to learn about the latest developments in bleeding disorders treatment, to discuss, to debate and to contribute to a strong global organization and community. This year’s Congress will feature presentations, workshops, and exhibits on cutting-edge trends in research and treatment for haemophilia and other inherited bleeding disorders.
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Retina International World Congress
Date: 14-15 July 2012
Venue: Hamburg, Germany
This congress, held every two years, includes: the latest information on diagnostics, therapy and disease management in diseases such as retinitis pigmentosa, AMD, Usher syndrome, Bardet-Biedl syndrome, Stargardt’s disease, Cone-rod dystrophy, and more; the latest in international research, and much more.
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7th European Elastin Meeting
Date: 1-4 September 2012
Venue: Ghent, Belgium
Topics include mechanisms of microfibrils and elastic fibres, heritable and acquired diseases, therapeutic advances and more.
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First International Symposium on the Ehlers-Danlos Syndrome
Date: 8-11 September 2012
Venue: Ghent, Belgium
Topics include natural history; clinical aspects; updated nosology; diagnostics guidelines; therapeutic and management strategies; animal models, and more.
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3rd Pan-European Conference on Haemglobinopathies and Rare Anaemias: Towards the Future
Date: 25–26 October 2012
Venue: Limassol, Cyprus
The Thalassaemia International Federation is delighted to announce the organisation of the 3rd Pan-European Conference, held under the auspices of the Cyprus Presidency and in close collaboration with the Cyprus Ministry of Health. The conference will bring together stakeholders to discuss avenues of action to tackle the growing public health burden of chronic and rare diseases in Member States and the EU.
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10th Asia-Pacific Conference on Human Genetics
Date: 5-8 December 2012
Venue: Kuala Lumpur, Malaysia
The APCHG2012 will examine various themes on personalised medicine, human variations in the Asia-Pacific region as well the latest advances on genetic diagnostics and technology and their implications to healthcare in the region. In addition, the APCHG2012 will also discuss issues pertaining to bioethics, genetics education and counselling as well as preventative strategies for birth defects and inborn errors of metabolism, and to provide a platform for patients and families to discuss emerging issues in individuals with inherited conditions and chronic disabilities..
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8th International Prader-Willi Syndrome Conference
Date: 17-21 July 2013
Venue: Cambridge, UK
An opportunity for all involved worldwide in research, working or living with people with PWS to present current research and explore best practice in clinical and day to day management of PWS.
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Media, Press & Publications
Children's Upper and Lower Limb Orthopaedic Disorders
This recent text covers general principles of pediatric orthopedic disease, neuromuscular disorders, and fractures, including both classic and contemporary article references for in-depth information on the described conditions and operative techniques. The upper limb chapters describe foetal development and how this may go wrong. As always, function dominates our management plans although cosmetic considerations must be borne in mind. The lower limb chapters consider limb deficiency and deformity and how to manage them. Those prominent afflictions of the child’s hip - dysplasia, Perthes disease and epiphyseal slipping - are fully discussed. Chapters on the common conditions affecting the knee, foot and ankle complete this section.
Title: Children's Upper and Lower Limb Orthopaedic Disorders
Authors: M. Benson, K. Parsch, M. Macnicol, J. Fixsen –Eds
Publisher: Springer (June 2011)
ISBN-13: 978-0857295606
Diagnosis and Management of Adult Congenital Heart Disease
This text offers a practical resource designed to help manage the unique challenges of treating long-term adult survivors of congenital heart disease. Authored by internationally known leaders in the field, this edition integrates anatomy and imaging technology into clinical practice, and includes new chapters on cardiac CT for ACHD assessment, critical and perioperative care, anesthesia for ACHD surgery, cardiac resynchronization therapy, and transition of care. Congenital defects are presented with high-quality illustrations and appropriate imaging modalities.
Title: Diagnosis and Management of Adult Congenital Heart Disease
Author: M.A. Gatzoulis, G.D. Webb, P.E.F. Daubeney
Publisher: Elsevier/Saunders (October 2010)
ISBN-13: 978-0702034268
Did Elizabeth Barrett Browning have a rare disease?
The advances in knowledge and technology are not only identifying current cases of rare disease, but are allowing older ones to be better understood. One of the best-known and loved poets of the English Victorian era, Elizabeth Barrett Browning (1806-1861), may have suffered from the rare muscular disease hypokalemic periodic paralysis, according to a researcher at Pennsylvania State University (USA), whose own daughter has the same condition. Browning, frequently described in the vernacular of her day as “frail” and “weak”, wrote prolifically despite her illness, leaving behind a body of critically acclaimed work, including the famous collection Sonnets from the Portuguese. Browning often took up the theme of social injustice in her work, as well as the topics of grief and love. Her sonnet Number 44 begins with one of the most well-known phrases in the English language:
How do I love thee? Let me count the ways
I love thee to the depth and breadth and height
My soul can reach, when feeling out of sight
For the ends of Being and ideal Grace.