16 April 2008 print
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Rare disease communication results online
The European Commission’s DG Health and Consumer Protection has posted online all the responses to the Consultation regarding European Action on Rare Diseases. Replies are organised into the following groups: Patients and their families, National patient organisations, International patient organisations, Member states (national authorities), International and European organisations, Commercial organisations, companies and their associations, Universities and other experts, Reference centres, Researchers, and Others. All the responses to the Consultation are considered valuable – and there were some notable contenders from the full spectrum of the rare disease stakeholders who weighed in on the subject - the European Medicines Agency’s Committee for Orphan Medicines Products (COMP), the Standing Committee of European Doctors, the EC Rare Disease Task Force, the European Cancer Patient Coalition, the Karolinska Institutet, the Slovenian PKU Association, the Association Prader Willi France, the Society for Inborn Errors of Metabolism in Adults in Internal Medicine, the Cyprus Institute of Neurology and Genetics, the Italian Medicines Agency, the Medical Genetics College at the Portuguese Medical Association, the Polish Association for Genetic Disorders in Children, BioMarin, Genzyme, Shire Human Genetic Therapies and EuroGentest are just some examples of the diversity of responses. Member state authorities responding to the Consultation include representatives from Denmark, France, Germany, Hungary, Malta, the Netherlands, Norway, Spain, Slovenia, Sweden and the UK.

The responses to the Consultation provide a rich resource yielding multiple perspectives. The individual replies from patients and parents of patients provide that crucial first-hand experience of what it truly is to live with a rare disease in Europe today – and what is needed to improve the quality of life for patients and their caregivers. The national and international patient groups possess in depth knowledge of a particular disease or group of diseases and are able to offer a unique perspective, including resources available and resources sorely missing. The health authorities hold particular information on the budgetry and legal obstacles that can prevent resources being created for patients, and the scientific and industry representatives are able to communicate what they need to go forward toward a better understanding of rare diseases and the development of therapeutic and diagnostic products for patients. OrphaNews Europe takes this moment to acknowledge all the various stakeholders who took the time to read and offer their thoughtful – and often thought provoking – reply to the Public Consultation for Rare Diseases: Europe’s Challenges.

The process of revising the rare disease communication in order to incorporate the various comments and suggestions made during the consultation period is already underway. The drafting group responsible for the task anticipates terminating the revision by the end of June. The modified document will then be presented and reviewed at the next bi-annual meeting of the Rare Disease Task Force, taking place in early July.
View the replies to the Consultation


EU Policy News
DG Enterprise
Consultation paper launched for advanced medicinal products implementation plan
Regulation (EC) 1394/2007 on advanced therapy medicinal products specifies rules concerning the authorisation, supervision and pharmacovigilance of advanced therapy medicinal products (gene therapy, somatic cell therapy and tissue engineering). This Regulation will apply from 30 December 2008. In December 2007, the European Commission (EC) published an implementation plan outlining its priorities for the implementation of the Regulation. This implementation plan has been developed and agreed with the European Medicines Agency (EMEA). As part of this plan, the EC intends to revise Part IV, Annex I to Directive 2001/83/EC in order to adapt it to the specificities of advanced therapy medicinal products. Now, a public consultation document is available presenting preliminary proposals to replace the existing Part IV of this Annex I. Comments on this document are invited from all stakeholders involved with advanced therapy medicinal products. Stakeholders who are not established within the European Union are equally invited to comment. Comments from Small and Medium-sized Enterprises in the sector are especially welcomed. Contributions should be sent via e-mail before 10 June 2008.
View the consultation paper


National & International Policy Developments
2008 designated Year of the Rare Disease Patient in Croatia
Since its registration as a non-profit humanitarian organisation in April 2007, The Croatian Society of Patients with Rare Diseases has been working on developing relations with the stakeholders who have an impact on the lives of rare diseases patients. The Society has established a cooperation with the Ministry of Health and Social Welfare, the Croatian Institute for Health Insurance and other national health institutions, national and European-level civil society organisations, and medical professionals who work with rare disease patients.

In 2007, the Society completed work on a series of public activities grouped under one name – Give me a hand – whose main goal was to inform and educate the Croatian public on rare diseases and the challenges patients face in their every day life, as well as to raise funds for future work.

The Society kicked off 2008 by presenting an initiative to the Croatian government to declare 2008 as The Year of the Rare Disease Patient. This initiative would enable the Society to make its work more visible via extensive media coverage and could also activate authorities, private business, the medical community and social welfare providers to give rare disease patients the most effective care possible. In January, representatives of the Croatian Society of Patients with Rare Diseases, including Board of Directors members, patients, and parents of children with rare diseases, visited the country’s president and presented the issues concerning rare diseases in Croatia. The President gave his support to the initiative to declare 2008 as the Year of the Rare Disease Patient and offered assistance in future activities.

As is now widely known, this year is special for one more reason: for the first time different countries contributed to the First European Rare Disease Day on 29 February. The Croatian Society of Patients with Rare Diseases was equally active on this special day - during a press conference the group emphasised that rare disease patients represent a minority and that it is imperative to diminish prejudices and to make public the challenges patients and their families face in their every day life. It is hoped that through lobbying and advocacy, capacity building, policy and legislation formulation, Croatia can improve the quality of life for its rare disease patients and their families.

Other European news
Généthon issues English-language newsletter
Généthon, a French non-profit biotechnology organisation, subsidised by the French Association against Myopathies via donations collected through its annual Téléthon, defines itself as an “integrated structure whose activities range from research to clinical development and integrating good manufacturing practices production with the aim of marketing gene therapies for rare diseases, mainly neuromuscular diseases”. Généthon has just published its first newsletter in English language. To appear quarterly, the Généthon newsletter provides a new venue through which to promote activities, publications, conferences and projects related to rare genetic diseases.
The Family Route Map Project creates a tool for rare disease information and services
The Family Route Map Project is designed to help patients and their families identify and access information and services available for rare conditions. Launched in April 2006 by the UK-based Genetic Interest Group (GIG), a national alliance of patient organisations, and funded by Jeans for Genes and a grant from Genzyme Therapeutics, the Family Route Map Project gathered the personal experiences of rare disease patients, their families, care givers and patient organisations. As is true across Europe, families with rare disorders often struggle to find an appropriate expert or specialist team to assess and advise them. The experiences of patients with six specific conditions - Barth syndrome, Gorlin syndrome, Multiple Endocrine Neoplasia Disorders, Myotonic Dystrophy, Nail Patella syndrome, and Syndromes Without A Name (SWAN) - were used. Information was gathered by listening to the concerns of patients, families and carers. Workshops were held for each condition in order to identify information and services currently available to families, as well to discover what patients and their entourage would like to see included. An online questionnaire disseminated via the GIG website with links to the websites of the six patient support organisations, and interviews with clinicians and other healthcare professionals with expertise and experience in these conditions were undertaken.

During the information gathering phase of the project, some recurring issues surfaced such as the need to identify sources of financial help, psychological support, information, and education. Seven over-arching themes were identified: Information; Communication; Diagnosis; Treatment and Surveillance; Education of Healthcare Professionals; Ethical, Legal and Social Issues; and Empowerment of patients, parents and carers. Many rare genetic condition patients reported receiving fragmented care and indicated a preference for one lead clinician acting in a coordinating role. Patients and their families seek relevant up-to-date information and more support to enable them to understand their condition and actively participate in their care. Only two of 57 patient focus group participants and 3 phone interviewees in the project reported being satisfied with the treatment and surveillance they or their affected family member(s) currently received.

The project findings have allowed for the development of a set of recommendations, including: up-to-date training and education in genetics for all healthcare professionals as part of their continuing professional development; greater awareness of rare genetic conditions amongst the medical profession could lead to earlier diagnosis for patients with rare genetic conditions; better communication between patients and professionals and also between professionals would enable patients to make informed choices; a referral to the Clinical Genetics Service should be offered to all patients; clearer guidelines for treatment and surveillance of rare genetic conditions are needed; to avoid fragmentation in their management, patients would like to receive coordinated care within a multidisciplinary team approach preferably at a Centre of Excellence; Centres of Excellence or Networks of Expertise need resources in order to offer services to rare disease patients to ensure equitable access to care; counselling and psychosocial provision should be made available to all who request it; practice nurses could be a resource in primary care for reliable sources of information and providing continuity of care with much needed psychological support. Another possible conclusion for the UK might be the creation of a new medical specialty of Genetic Medicine. The Family Route Maps Project has created a powerful tool to help families, patient organisations and healthcare professionals access appropriate information and services in the UK. A generic template is available free from GIG for any patient support organisation to use in order to develop a Family Route Map for the condition(s) within their own membership. Read the Family Route Map Project final report.

Other International News
American Cancer Society releases global facts and figures for 2007
The American Cancer Society has released its annual global statistics concerning cancer rates. Childhood cancers, all of which are rare, remain a leading cause of death in paediatric populations in developed countries. For developing countries, incidence is harder to measure, due to a lack of reporting and the comorbidity of other conditions such as malnutrition and infectious disease. That said, some 80% of the world’s children with cancer live in developing countries. Leukaemia remains the most common form of childhood cancer worldwide except for parts of Africa, which have a higher incidence of Kaposi sarcoma and Burkitt lymphoma. Of the estimated 161,000 new cases occurring in children aged 0-14 years in 2007, incidence rates are higher in developed versus developing countries, due in part to improved diagnostics in these countries. Despite the higher incidence rates in developed countries, mortality rates are lowest in these regions, due to better access to treatment. An estimated 87,000 children died from cancer in 2007 globally. The report concludes that mortality from childhood cancers, and particularly leukaemia, have declined sharply in the last 40 years in developed countries, despite the fact that the cancer incidence rates are increasing, and for reasons other than improved diagnostics, in some developed regions. Infection-related cancers, such as Burkitt leukaemia, Hodgkin disease, nasopharyngeal cancers, liver carcinoma, or Kaposi sarcoma, are common regionally in developing countries. Read the full report. Another interesting study of childhood cancers can be found in a special issue of the European Journal of Cancer, featuring 20 articles dedicated exclusively to cancers in children and adolescents in Europe.

Ethical, Legal & Social Issues
Two recent articles review human gene transfer ethical issues
Two articles have been published recently examining ethical issues relating to the emerging technology of gene transfer. The first, entitled En Route to Ethical Recommendations for Gene Transfer Clinical Trials appears in the March issue of Molecular Therapy. The article summarises a “joint think tank” held by Clinigene NoE and Consert, two European Union programmes working to facilitate the development of safe and effective human gene transfer. Several concerns surrounding these new technologies are considered: As what stage of development should a study involve human subjects? What are specific risks possibly encountered during gene transfer clinical trials? How to evaluate the risks and benefits of intentional germ line modifications? Should gene therapy be reserved uniquely for severe illnesses that have no other therapeutic options? Issues linked to the reimbursement of these therapies for rare diseases are also addressed.

A second article, by an American researcher specialising in ethical, social and political aspects of biotechnology, was published recently in Nature Review Genetics also exposes concerns arising from human gene transfer therapy. This study, entitled The ethics of human gene transfer is based on concrete examples arising from therapeutic trials and from national and international political decisions, and develops along two axes: somatic gene transfer and germ line gene transfer. Concerning the modification of somatic cells, the author examines the difficulties in evaluating the risks encountered by patients undergoing these techniques versus other biotechnologies. The article also reviews the ethical problems linked to the decision to begin trials in humans and the difficulty of cost and access to these technologies. The second part of the article is devoted to germ line modifications (voluntary or involuntary) and whether the technique should be applied to the enhancement of traits.


Orphanet News
New Texts
New Orphanet publication
Fragile X syndrome (published in the European Journal of Human Genetics, in association with Orphanet)


New Syndromes
NF1 microduplication: mild mental retardation, early onset of baldness and dental enamel hypoplasia
Neurofibromatosis type 1 is an autosomal dominant disease caused by mutations in NF1 gene. In around 5% of cases, the chromosome 17 region containing NF1 and up to 12 neighbouring genes is deleted. NF1 microdeletion carriers present a more severe phenotype than patients with intragenic mutations, including mental retardation, cardiac anomalies and dysmorphic features. Here, the authors report on seven cases within two generations of the same family presenting a microduplication of the NF1 microdeletion syndrome region. Main phenotypic features are mental deficiency, early onset of baldness (15 years old), dental enamel hypoplasia and minor facial dysmorphism. While similar phenotypic abnormalities were present in most of the individuals, two displayed a normal phenotype, suggesting a potential incomplete penetrance of the phenotype associated with NF1 microduplication.
Read the PubMed abstract

European Journal of Human Genetics ; 305-311 ; March 2008
STAR syndrome: Syndactyly, Telecanthus and Anogenital and Renal malformations
The authors describe four unrelated girls with a consistent constellation of facial dysmorphism and malformations previously reported in a single mother-daughter pair. Toe syndactyly, telecanthus and anogenital and renal malformations were present in all affected individuals. Causative mutations were found in gene FAM58A on chromosome X, suggesting an X-linked dominant inheritance pattern for this syndrome.
Read the PubMed abstract

Nature Genetics ; 287-289 ; March 2008
15q13.3 microdeletion: mental retardation, seizures and dysmorphia
The authors describe nine affected individuals with mental retardation, epilepsy and variable facial and digital dysmorphisms. All present 15q13.3 microdeletions, inherited or de novo, containing at least six genes. The frequency of these microdeletions in mental retardation cases is approximately 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes.
Read the PubMed abstract

Nature Genetics ; 322-328 ; March 2008

New Genes
Woolly hair syndrome: an orphan G protein-coupled receptor underlies the condition
The genetic determinants of hair texture in humans are largely unknown. Several human syndromes exist in which woolly hair comprises a part of the phenotype; however, simple autosomal recessive inheritance of isolated woolly hair has only rarely been reported. To identify a gene involved in controlling hair texture, the authors performed genetic linkage analysis in six families of Pakistani origin with autosomal recessive woolly hair. In all cases, pathogenic mutations were found in P2RY5 gene, which encodes a G protein-coupled receptor and is a nested gene residing within intron 17 of the retinoblastoma 1 (RB1) gene. P2RY5 is expressed in layers of the inner root sheath of the hair follicle. This study teases out a new gene involved in determining hair texture in humans.
Read the PubMed abstract

Nature Genetics ; 335-339 ; March 2008
Ghosal syndrome: Platelets from patients show a deficit in arachidonic acid-produced aggregation
Ghosal hematodiaphyseal dysplasia syndrome (GHDD) is a rare disorder characterised by increased bone density (predominantly diaphyseal) and aregenerative corticosteroid-sensitive anemia. Studying consanguineous families with GHDD, the authors identified mutations in TBXAS1, which encodes thromboxane synthase (TXAS). TXAS, an enzyme of the arachidonic acid cascade, produces thromboxane A(2) (TXA(2)). Platelets from subjects with GHDD showed a specific deficit in arachidonic acid-produced aggregation.
Read the PubMed abstract

Nature Genetics ; 284-286 ; March 2008
ATP synthase deficit: a mutation in the mitochondrial ATP8 gene is identified
The authors describe a 16-year-old patient presenting with apical hypertrophic cardiomyopathy and neuropathy suspected for a mitochondrial disorder. This phenotype is accompanied by a deficit of ATP synthase, an enzymatic activity belonging to complex V of the mitochondrial respiratory chain. Analysis of the genes encoding the subunits of this complex led to identification of a mutation in the mitochondrial gene ATP8.
Read the PubMed abstract

Journal of Medical Genetics ; 129-133 ; March 2008

Research in Action
Clinical Research
Neurofibromatosis 1: recommendations for supervision and management
Neurofibromatosis 1 is a multisystem disorder with a prevalence of 1 in 3500 that primarily involves the skin and nervous system. The condition usually is recognized in early childhood, when cutaneous manifestations are apparent. Although neurofibromatosis 1 is associated with marked clinical variability, most affected children do well from the standpoint of their growth and development. Some features of neurofibromatosis 1 are present at birth, and others are age-related abnormalities of tissue proliferation, which necessitate periodic monitoring to address ongoing health and developmental needs and to minimize the risk of serious medical complications. This clinical report provides a review of the clinical criteria needed to establish a diagnosis, the inheritance pattern of neurofibromatosis 1, its major clinical and developmental manifestations, and guidelines for monitoring and providing intervention to maximize the growth, development, and health of an affected child.
Read the PubMed abstract

Pediatrics ; 633-642 ; March 2008
Rett syndrome: an increased risk of fractures
Rett syndrome is a severe neurodevelopmental disorder affecting the central nervous system and primarily affecting females. Osteoporosis is a frequently seen complication. The Australian Rett syndrome study, a population-based study operating since 1993, investigated 234 Australian subjects with Rett syndrome born since 1976. The main outcomes were fracture incidence in the Rett syndrome population and fracture risk according to genotype, presence of epilepsy, and early motor profile. Fracture incidence in this cohort was nearly 4 times greater than the population rate. Having epilepsy also increased fracture risk, even after adjustment for genotype.
Read the PubMed abstract

Pediatrics ; 540-546 ; March 2008
Optic nerve hypoplasia: 71% of patients present developmental delays
Optic nerve hypoplasia is a congenital anomaly characterised by optic nerve developmental disorders in one or both eyes. The authors conducted a prospective analysis of 73 subjects diagnosed with optic nerve hypoplasia at <36 months of age for developmental outcomes at 5 years of age. At 5 years of age, developmental delay was present in 71% of subjects with optic nerve hypoplasia. Corpus callosum hypoplasia and hypothyroidism were significantly associated with poor outcome in all of the developmental domains and an increased risk of delay. A diagnosis of optic nerve hypoplasia warrants neuroradiographic and endocrinologic testing for risk factors of delay and developmental assessments for early intervention planning.
Read the PubMed abstract

Pediatrics ; e653-e659 ; March 2008
Pulmonary arterial hypertension: serum markers associated with risk of death in children
Pulmonary arterial hypertension is a rare condition characterised by elevated pulmonary arterial resistance leading to right heart failure. Appropriate parameters are needed for the monitoring of children with this condition. In this study, the relation between serum markers, functional parameters, and hemodynamic variables in paediatric pulmonary arterial hypertension and their ability to predict survival is determined. Serum N-terminal pro brain natriuretic peptide (NT-proBNP), uric acid, norepinephrine, and epinephrine were measured and correlated with invasive hemodynamics, functional parameters, and outcome in 29 paediatric patients. Norepinephrine and NT-proBNP levels were highly predictive for mortality. The data indicate that these markers can be used to monitor treatment effects and predict mortality in paediatric pulmonary arterial hypertension.
Read the PubMed abstract

Pediatric Research ; 321-327 ; March 2008
Turner syndrome patients have increased cancer risk
Turner syndrome is a chromosomal disorder associated with the complete or partial absence of an X chromosome. Its incidence has been estimated at 1 in 5000 live births (1 in 2500 female births). Clinical features are heterogeneous and typical physical anomalies are often mild or absent. Short stature is present in all cases. Ovarian failure, with variable onset depending on the chromosomal anomalies, is frequent. The authors studied a cohort of 3425 women who were cytogenetically diagnosed with Turner syndrome in Great Britain between 1959 and 2002 to compare the risk of cancer in women with this syndrome with that of the general population. This study shows that, in addition to having an increased risk of gonadoblastoma, women with Turner syndrome seem to be at increased risk for meningioma and childhood brain tumours, and possibly bladder cancer, melanoma, and corpus uteri cancer, but are at a decreased risk for breast cancer. Reasons for these risks might relate to genetic and hormonal factors or to the effects of hormonal treatments given to women with Turner syndrome.
Read the PubMed abstract

Lancet Oncology ; 239-246 ; March 2008
Cockayne syndrome: severe forms are not caused by truncating mutations
Cockayne syndrome is rare autosomal recessive inherited condition that develops between the ages of 1 and 2. Diagnosis is based on clinical findings: poikilodermia, dwarfism, mental retardation, pigmentary retinopathy, blindness and conduction hearing loss. Most cases of Cockayne syndrome are caused by mutations in the CSB gene but the pathophysiological mechanisms are poorly understood. The authors report the clinical and molecular data of two severely affected Cockayne patients with undetectable CSB protein and mRNA. Both patients showed severe growth failure, microcephaly, mental retardation, congenital cataracts, retinal pigmentary degeneration, photosensitivity and died at the ages of 6 and 8 years. A recent study proposed that all type of CSB mutations result in a defect in UV damage repair that is responsible for the photosensitivity observed in the syndrome, but that only truncated CSB polypeptides generated by nonsense mutations have some additional inhibitory functions in transcription or in oxidative damage repair, which are necessary to lead to the other features of the phenotype. However, the patients in this study do not fit the proposed paradigm and new hypotheses are required to account for the pathophysiology of Cockayne syndrome.
Read the PubMed abstract

European Journal of Human Genetics ; 320-327 ; March 2008
Huntington disease: a study of genetic discrimination
Huntington disease (HD) is a neurodegenerative disorder of the central nervous system, mainly affecting the basal ganglia (caudate nuclei and putamen). The disease affects females and males and usually occurs in adults. Onset is often insidious, either with motor abnormalities (choreic syndrome), or with personality or behavioural changes, and even psychiatric disturbances (depression). Alongside the progression of motor disorders leading to falls, dysarthria and difficulties to swallow, dementia sets in. It has been over 20 years since the inception of predictive testing for Huntington disease, yet the social implications of knowing one's genetic risk for HD have not been fully explored. Genetic discrimination is a potential risk associated with predictive testing. The purpose of this study was to describe the concerns and experiences of genetic discrimination in the HD community. Semistructured interviews were conducted with 45 genetically tested and 10 untested individuals and analysed using grounded theory methods. Findings demonstrate that a majority of individuals were concerned about discrimination across a variety of contexts that extend beyond the traditionally examined contexts of insurance and employment to include family, social, government, and health-care domains. These results help identify areas where more education and support is needed and provide direction to genetic professionals supporting their clients.
Read the PubMed abstract

European Journal of Human Genetics ; 279-289 ; March 2008
X-linked congenital ataxia: a second locus identified
Different means of transmission have been described for patients with congenital ataxia: autosomal recessive, autosomal dominant, or recessive X-linked. The authors report on a large American family of Norwegian descent with X-linked nonprogressive congenital ataxia for which the disease transmission is associated with a new locus: Xq25-q27.1. The identification of this second locus demonstrates the genetic heterogeneity of the disease.
Read the PubMed abstract

The American Journal of Medical Genetics ; 593-600 ; March 2008
Therapeutic Approaches
Morquio A syndrome: enzyme replacement therapy in a murine model yields encouraging results
Mucopolysaccharidosis type IV A, also known as Morquio A syndrome, is a lysosomal storage disease characterised by spondylo-epiphyso-metaphyseal dysplasia. It is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), leading to accumulation of keratan sulfate (KS) and chrondroitin-6-sulfate. The authors administered variable doses of enzyme replacement by injection into murine models. After 12 weeks, they observed a reduction in the accumulation of keratin sulfate in different organs, including the brain.
Read the PubMed abstract

Human Molecular Genetics ; 815-824 ; March 2008
Diagnostic Approaches
Preimplantation genetic diagnosis: provision and quality assurance in Europe
Preimplantation genetic diagnosis is now well established and provided in many European countries. However, regulations, professional standards and accreditation requirements can differ notably. Furthermore, no comprehensive independent data exist for practice and provision in Europe or for quality assurance practices and procedures designed to optimise the quality of the results. This study gathered information from 53 centres offering preimplantation genetic diagnosis in 17 European countries. Although half of the centres have a designated quality manager, just 33% have achieved or are preparing for accreditation or certification. About 66% of the centres responded that they did not participate in external quality assessment, a problem exacerbated by the lack of existing specific schemes. Approximately 19% of the centres do not keep data on accuracy and 9% do not follow up until birth. This survey highlights that although these preimplantation genetic diagnosis centres are usually highly qualified, improvements could be made in terms of quality assurance.
Read the PubMed abstract

European Journal of Human Genetics ; 290-299 ; March 2008

Patient Management and Therapy
Langerhans cell histiocytosis: therapy intensification improves outcome
Langerhans cell histiocytosis refers to the oligoclonal proliferation of Langerhans cells that occurs in children and young adults. Clinical presentation is variable, ranging from a single location in the bone to severe multivisceral involvement (i.e lungs, bone marrow, liver, spleen) leading to dysfunction of vital organs. In an international randomized trial, the authors intensified patient treatment: arm A consisted of 6 weeks of daily prednisone and weekly vinblastine followed by 18 weeks of daily 6-mercaptopurine with vinblastine/prednisone pulses; etoposide was added in arm B. Considering all 193 randomized risk patients, there were similar outcomes. However, intensified treatment increased rapid response and reduced mortality in risk cases.
Read the PubMed abstract

Blood ; 2556-2562 ; March 2008
Still disease: anakinra treatment more efficacious in adult forms of the disease
Anakinra treatment has been reported to be effective in some patients with systemic-onset juvenile idiopathic arthritis or adult-onset Still disease, both rare inflammatory diseases. 35 patients were treated with anakinra. Treatment was more effective in adult Still disease patients, whereas less than half of the juvenile idiopathic arthritis patients achieved a marked and sustained improvement.
Read the PubMed abstract

Annals of the Rheumatic Diseases ; 302-308 ; March 2008
Juvenile dermatomyositis: adverse reactions are associated with immunoglobulin A content
Dermatomyositis is an inflammatory muscle disease defined by characteristic skin symptoms (photosensitive erythroedema on exposed areas), muscle weakness, inflammation of the pharyngeal muscles causing deglutition disorders and requiring emergency hospitalization in specialized units. In this study, the authors sought to determine whether different intravenous immunoglobulin products used in the treatment of juvenile dermatomyositis are equally well tolerated by patients. Of the 38 children evaluated, significant differences existed in tolerance to different intravenous immunoglobulin products, most likely because of immunoglobulin A concentration. This study confirms anecdotal reports that a high level of immunoglobulin A in intravenous immunoglobulin is less well tolerated by children.
Read the PubMed abstract

Pediatrics ; e626-e630 ; March 2008
Cancer predisposition syndromes: Genetic testing and tumour surveillance recommendations
Genetic testing for the presence of germline mutations in cancer-predisposing genes can identify individuals at increased cancer risk. For these individuals, the institution of cancer surveillance measures is recommended with the aim of detecting cancers at early and hence more curable stages. While these principles are well established in adults, they are only entering the paediatric arena. The authors of this study describe recent findings related to genetic testing and cancer surveillance in three conditions marked by the development of tumours during childhood: retinoblastoma, Beckwith-Wiedemann syndrome/idiopathic hemihypertrophy, and Wilms tumour-associated syndromes. The integration of clinical genetic testing and cancer monitoring has favourably influenced the survival and quality of life for patients. Future research focusing on enhancing the sensitivity of genetic testing and efficacy of surveillance for at-risk populations could further decrease the morbidity and mortality associated with these conditions.
Read the PubMed abstract

Current Opinion in Pediatrics ; 1-7 ; February 2008
Whipple disease: new aspects of pathogenesis and treatment
Whipple disease is a chronic multisystemic disease. The infection is very rare, although the causative bacterium, Tropheryma whipplei, is ubiquitously present in the environment. This study reviews the epidemiology of Whipple disease and the recent progress made in the understanding of its pathogenesis and the biology of its agent. The clinical features of the disease are non-specific and sensitive diagnostic methods such as PCR with sequencing of the amplification products and immunohistochemistry to detect T whipplei are still not widely distributed. The best course of treatment is not completely defined, especially in relapsing disease, neurological manifestations, and in cases of immunoreconstitution after initiation of antibiotic treatment. Patients without the classic symptoms of gastrointestinal disease might be misdiagnosed or insufficiently treated, resulting in a potentially fatal outcome or irreversible neurological damage. The authors suggest procedures for the improvement of diagnosis and an optimum therapeutic strategy.
Read the PubMed abstract

Lancet Infectious Diseases ; 179-190 ; March 2008

Orphan Drugs
UK debate reveals complexity of orphan drug cost issues
Pulmonary arterial hypertension (PAH) is a very rare disorder of high blood pressure in the pulmonary arteries, causing the arteries to thicken and narrow, restricting blood flow in the lungs. It is not curable and leads to premature death if left untreated. Following a recommendation from independent health guidance body the National Institute for Health and Clinical Excellence, promoting less effective treatments for PAH that also happen to be much less expensive, a debate was organised at the British House of Commons to agitate support for PAH patients who want access to the more effective, higher-priced treatments. These treatments, which consist of the prostacyclins epoprostenol and iloprost, do not fall within the current NICE recommended threshold of £20,000 to £30,000 per QALY (quality-adjusted life years). Indeed, the prostacyclin treatments cost some patients £100,000 per year. The debate was organised in an attempt to persuade NICE to revisit its decision. The outcome could have repercussions for other rare disease products, in particular some of the pricey ultra orphan treatments, more of which are expected to become available in coming years. OrphaNews Europe will follow this story and report on the eventual outcome. The UK, like most European countries, is struggling to find room in its health budget for expensive yet life saving rare disease treatments.
Read the transcript of the House of Commons debate
Read the NICE appraisal consultation document


Research proposals being accepted by the ELA Foundation
Established in 2004, the ELA Foundation is a non-profit charitable organisation that promotes advancement in science through research programmes and educational projects. The ELA Foundation now invites the international scientific community to submit research applications in the field of genetic leukodystrophies, cerebral white matter injury of the premature infant and myelin repair.

Application submission deadline: 25 May, 2008.
For more information, contact the ELA Foundation


Partnersearch, Job Opportunities
Spanish institute seeks partners for Burkitt lymphoma research
Spanish research institute Consejo Superior de Investigaciones Cientificas has patented a new method for the accurate diagnosis of sporadic Burkitt lymphoma and for the identification and employment of novel and potentially less toxic therapies for this disease than those currently in use. The institute is interested in establishing agreements with biotech and pharmaceutical companies. Contact the institute

What's on Where?
International Ataxia-Telangiectasia Workshop 2008
Date: 22-26 April 2008
Venue: Kyoto, Japan

Topics include the roles of ATM and its related proteins in the DNA damage responses and in the tumorigenesis. The biological roles of ATM in the development of immune system, nervous system, and the stem cell systems are another essential area towards new therapies for A-T.
For further details

Second International Workshop on Minicircle-DNA
Date: 7-9 May 2008
Venue: Bielefeld, Germany

Following on the success of the 2007 conference, and focusing on technology and IP and application. The workshop is supported by CLINIGENE, the European Network of Excellence for the advancement of clinical gene transfer and therapy. CLINIGENE is offering 10 grants (500 Euros) for trainees or post-docs attending this meeting. Please contact CLINIGENE for further information.
For further details

First International Meeting of Moebius Syndrome
Date: 16-17 May 2008
Venue: Valencia, Spain

Held in English and Spanish, the conference will focus on cranial nerves and brain stem; Moebius syndrome or sequence; natural history of Moebius syndrome; rare diseases and Moebius syndrome; ophthalmological problems; deglutition problems; oral health in Moebius; speech-language therapy; club feet in Moebius; Poland anomaly in Moebius syndrome; genetics of Moebius syndrome; psychological support; facial surgery (Zuker’s facial animation surgery); and living with Moebius syndrome: personal experiences of affected people.
For further details

ICORD 4th International Conference on Rare Diseases and Orphan Drugs
Date: 20-22 May 2008
Venue: Washington, DC US
For further details

13th International Conference for Behçet's Disease and 5th Patients' Convention
Date: 24-27 May 2008
Venue: Klagenfurt, Austria

With presentations and discussions on oral, eye, genital and skin involvement, as well as paediatric patients, drug trials and future perspectives.
For further details

Myology 2008: Treatments – The Turning Point
Date: 29 May - 1 June 2008
Venue: Marseilles, France

Focusing on the development of therapies and the setting up of trials on humans for rare diseases in the field of myology.
For further details

First Conference on Translational Research in Paediatric Rheumatology
Date: 29 May - 1 June 2008
Venue: Genoa, Italy

Using the field of rare paediatric rheumatic disorders as a paradigm, Anticipating Changes in Drug Development for Children: Building on Paediatric Rheumatology will examine the medicine research and development process, from pre-clinical and early-phase clinical development, to biomarker validation, study design and management, data analysis, ethical review, regulatory submission and research governance. The conference is meant to further stimulate interaction among the three major stakeholders in the drug development process, namely, academia, industry and regulatory authorities.
For further details

5th International Congress of Rehabilitation in the Field of Neuromuscular Disorders
Date: 30 May – 1 June 2008
Venue: Marseilles, France

With sessions on gene-based therapies, patient evaluation, pain and fatigue management, and treatment options.
For further details

EuroGentest Genetic Testing Accreditation and Quality Assurance Programmes
Date: 30-31 May 2008
Venue: Barcelona, Spain

EuroGentest presents two workshops and a round table session on the topics of accreditation in genetic testing labs, quality assurance and managing the human side of change.
For further details

International Down Syndrome Screening Group 8th International Congress
Date: 31 May- 1 June 2008
Venue: Vancouver, Canada

Held in conjunction with the International Society for Prenatal Diagnosis conference, taking place immediately afterward.
For further details

40th European Human Genetics Conference
Date: 31 May-3 June 2008
Venue: Barcelona, Spain

In conjunction with the European Meeting on Psychosocial Aspects of Genetics 2008. Progamme will cover the latest developments in the field of human genetics that are of interest both for clinicians and research scientists.
For further details

14th International Conference on Prenatal Diagnosis and Therapy
Date: 1-4 June 2008
Venue: Vancouver, Canada

Conference sessions will include foetal imaging, cytogenetics, foetal DNA/RNA, PGD, screening, teratology, and legal aspects of prenatal diagnostics and therapy.
For further details

5th International Cystinosis Conference
Date: 27-28 June 2008
Venue: Dublin, Ireland

World experts in the field of Cystinosis will attend and the latest research in this very rare disease will be presented. The event is unique as it combines a high-level scientific and medical conference as well as being a family and patient friendly conference. Deadline for abstracts: 11 April 2008.
For further details

Fourth International Neuroacanthocytosis Symposium: Bridging Clinical and Basic Aspects
Date: 1-2 July 2008
Venue: Oxford and London, England

Including clinical aspects of chorea acanthocytosis and McLeod syndrome, muscle and nerve neuropathology and syndromes related to NA.
For further details

15th Retina International World Congress
Date: 4-5 July 2008
Venue: Helsinki, Finland

Clinical diagnostics of retinal dystrophies, genetic diagnostics and research, Usher syndrome, ongoing clinical trials. Deadline for abstract submission is 30 April, 2008.
For further details

Fourth International Conference on Metals and Genetics
Date: 21-24 July 2008
Venue: Paris, France

The main topics will include metal-associated diseases: molecular and systemic biology approaches; characterisation and speciation of metal in proteins and biological tissues; and metals and environmental health implications.
For further details

Barth Syndrome: On Track Toward a Cure - 4th International Conference
Date: 21-26 July 2008
Venue: Florida, USA

This conference will be dedicated to increasing knowledge and accelerating advances in research for this rare metabolic genetic disorder. It will bring together basic scientists, clinical researchers, treating physicians, other professionals, and affected individuals and families to focus on the syndrome through a series of carefully organised sessions.
For further details

15th Paediatric Rheumatology European Society Congress
Date: 14-17 September 2008
Venue: University College London, UK

The programme will cover four main topics through keynote lectures, abstract presentations and educational workshops: juvenile arthritis, juvenile dermatomyositis, vasculitis and pain. There will be novel symposia such as sport and exercise in young people.
For further details

13th International Meeting of the World Muscle Society
Date: 29 September - 2 October 2008
Venue: Newcastle upon Tyne, UK

New Insights into the pathogenesis of facioscapulohumeral muscular dystrophy, myotonic dystrophy and other dominant muscular dystrophies, Advances in the understanding and treatment of myasthenic disorders, Therapeutic advances in neuromuscular disorders, Advances across the neuromuscular field, including treatment and management.
For further details

6th World Rett Syndrome Congress
Date: 10-13 October 2008
Venue: Paris, France

Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
For further details

Tenth International Meeting on Osteogenesis Imperfecta
Date: 15-18 October 2008
Venue: Ghent, Belgium

Topics include: Bone homeostasis, murine models/collagen biology/biophysics, classification, genetics: genotype-phenotype, prenatal diagnosis/preimplantation diagnosis, biphosphonates, orthopedic management, hearing loss: physiopathology, surgery and imaging, other medical management issues, stomatology/dentistry, psychosocial aspects, new (therapeutic) perspectives.
For further details

EPPOSI 9th Workshop on Partnering for Rare Diseases Therapy Development
Date: 16-17 October 2008
Venue: Paris, France

Mark your calendars for the 2008 EPPOSI workshop, taking place at the National Assembly in Paris. The theme of the workshop is Orphan drugs: partnering along the chain and across the borders - Sharing strategies and tools for access to diagnosis and treatment.
For further details


Press & Publications
A report on a web-based registry for rare paediatric lung diseases
In the May issue of Pediatric Pulmonology, authors from the UK describe their experience in establishing a low-cost online registry for paediatric orphan lung diseases. The British Paediatric Orphan Lung Disease (BPOLD) electronic registry provides a web-based tool for reporting incidence on a monthly basis for nine rare respiratory diseases via a secure, confidential email reporting system. The original design has been tweaked since its conception to improve response rate - participating clinicians now receive a monthly electronic reminder to report new cases and update existing ones. The authors report that this low-cost method for establishing a registry is successful and can contribute to improving the understanding of the pathophysiology and management of paediatric orphan lung diseases. The website housing the registry also serves as an information source for clinicians and parents, and includes a description of the diseases, contact information and a discussion forum for parents.
Report from the EPPOSI workshop on patient safety
A new report has been issued summarising the discussion and conclusions of a workshop held in Luxembourg on 4 December, 2007, entitled Best Practices in Communicating Risks and the Value of Safety to Patients with Chronic Diseases. Hosted by the European Platform for Patients' Organisations, Science, and Industry (EPPOSI), with support from DG Sanco, the workshop brought together patient representatives from rare disease organisations such as IPOPI (primary immunodeficiencies), the World Federation of Haemophilia, and the Society for Mucopolysaccharide and Related Diseases, along with industry, government and research experts to discuss issues such as Optimising communication on risk, safety and benefit of therapy, Critical elements in informed consent for therapy, Legislation, and Forseeen and Unforeseen Risks. Breakout sessions were held, along with an open forum for discussion, culminating in a set of basic assumptions and recommendations for enhancing patient safety. Read the EPPOSI report


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
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Editorial Board: Ségolène Aymé, Catherine Berens, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
For more information on the Rare Diseases Task Force
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