19 March 2008 print
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EC rare disease consultation reaps unprecedented number of responses
The Public Consultation for a future Communication on European Action in the Field of Rare Diseases, entitled Rare Diseases: Europe's Challenges, drafted by the European Commission in close collaboration with the Rare Diseases Task Force, has culled the largest response ever for a public consultation. More than 600 contributions were received by the EC during the consultation period that ran from mid-November until 14 February, outdistancing the previous contender for most responses by over 400 comments. The average number of responses to a consultation is 60. This overwhelming reaction is being taken as a sign of proof of the pertinence of the Consultation on Rare Diseases and the desire across Europe to see its provisions implemented in the near future. France led the European countries with over 130 replies received, but responses came from most of the EU Member States and from all the rare disease stakeholders - international patient associations (64), national patient associations (156), individual patients and families (52), member state health authorities (26), regional authorities (16), centres and networks of reference (12), universities (40), research centres (4) and others. The text of the Consultation was generally supported, with three particular points evoking contrariant opinions: the use of prevalence versus incidence to define a rare disease; the necessity of European legislation specific to medical devices for rare diseases; and the proposal to create a European-level rare disease agency. All responses to the Consultation are being reviewed for inclusion in the final version of the text. After incorporating the suggestions received from the Public Consultation and the impact assessment of the EU services, the Communication will be presented to the European Parliament (most likely in September), and the Council of Ministers, the Economic and Social Committee, and the Committee of Region (hopefully by the end of the year). It is expected that the Parliament and the Council of Ministers will issue Recommendations on how to implement the suggested actions presented in this Communication. The responses to the Consultation will soon be available online, but OrphaNews Europe advises you to prepare your reading glasses and find a comfortable chair – the Consultation responses will make for over one thousand pages of reading!

EU Policy News
EUPHIX - A new tool designed to enhance public health knowledge
EUPHIX – the European Public Health Information and Knowledge System - is a new internet service that seeks to enhance public health knowledge on several fronts. EUPHIX is funded by the EU Public Health Programme 2003-2008 of the European Commission's Directorate General for Health and Consumer Affairs (DG SANCO), with co-financing from the National Institute for Public Health and the Environment in the Netherlands. The site includes data on health determinants, interventions, policies, demography and more. It provides special insight into disparities and similarities between individual EU countries. EUPHIX, serving policy makers and other professionals as well as interested citizens, also provides a platform for EU public health project results. It is hoped that rare disease knowledge and data will be represented on this useful new web-based system.
DG Research
CORDIS creates new FP7 health research web service
CORDIS, the European Commission's Research and Development Information Service, has created a new internet service that will provide information specific to the Seventh Framework Programme’s health research programme. The new information portal contains support for research applications, proposal negotiation, project management and small- and medium-sized enterprises, as well as sections on international cooperation, a library of relevant documents, national contact points for accessing further information, and useful links. Rare diseases are specifically listed in the FP7 pillar Translating research for human health.
Visit the new website

EMEA implemention strategy for developing EU paediatric network released
Regulation (EC) No 1901/2006 (the Paediatric Regulation) came into effect on 26 January 2007 to stimulate research and development of medicines for use in children, ensure that medicines for children are appropriately tested and authorised, and improve information availability. Article 44 of this regulation calls for the development of a pan-European network of existing national and European investigators and expert centres in the performance of medicinal product studies in the paediatric population. On 15 January of this year, an implementation strategy for developing this network was released. The objectives of the European network are to coordinate studies relating to paediatric medicinal products, to build up the necessary scientific and administrative competences at the European level, and to avoid duplication of studies and testing in children. The first step is to identify an inventory of existing networks, centres and investigators with specific paediatric expertise. Beside EU-funded networks and projects, these could also include patients, parents and families, and organisations representing children and patients; paediatric and other relevant learned societies; academia, including cooperative research groups, methodologists and other relevant groups; government-funded research institutions (including outside EU); research funding bodies; national Competent Authorities (for authorisation of trials or medicines authorisation, GCP and GMP compliance evaluation); paediatric health care providers; government-funded health services and national health systems; ethics committees and investigational review boards; the pharmaceutical and medical devices industries; clinical research organisations; hospital pharmacists; and laboratories and imaging centres Any relevant information concerning resources appropriate to the paediatric network can be sent by email. The Implementing Strategy presents specific short-and long-term objectives, an organisation and structure, and a proposed action programme of timelines and deliverables.
View the Implementation Strategy


National & International Policy Developments
Human-animal hybrid embryos permitted in the UK
In the United Kingdom, the Human Fertilisation and Embryology Authority (HFEA) License Committee has taken the decision to grant two licenses allowing scientists to conduct research using human-animal hybrid embryos. This decision came after a year of deliberating ethical and legal aspects of this type of research. The HFEA in January granted one-year licenses to scientists at King's College London and the University of Newcastle, permitting them to create a specific kind of inter-species hybrid by injecting human DNA into a hollowed-out animal egg cell. Britain is considered a leader in the field of stem cell research, attracting scientists from all over the world. The permission to create hybrid embryos provides scientists with a reliable source of stem cells that can be used to undertake vital research into life threatening conditions, including many rare diseases.
Read more about the HFEA decision

Other European news
The first E-Rare funded projects have been chosen
E-Rare has announced 13 projects selected for funding from its first call for proposals. E-Rare, the ERA-Net research programme for rare diseases, is a network of partners made up of public bodies, ministries and research management organisations from eight different countries responsible for the development and management of transnational research programmes on rare diseases. E-Rare is supported by the European Commission under the Sixth Framework Programme ERA-Net scheme for a 4-year period (starting June 1st 2006). The call for proposals was launched in March 2007 and was unrestricted in terms of disease, research or treatment approach. The call received 134 proposals with an average of 3-5 research teams per project. A wide variety of medical disciplines were represented in the call, a reflection of the extreme diversity of rare diseases. After months of evaluation, the Scientific Counsel, composed of international experts, managed to choose 13 projects. The 69 research teams making up these 13 projects will receive funding from a budget total of nine million euros. Diseases include craniofacial malformations, autoimmune liver diseases, Rett syndrome, spastic paraplegias, Hirschsprung disease, Kindler syndrome, and spinocerebellar ataxia, amongst others. Four of the projects chosen explore new therapeutic approaches. The complete results of the call are available on the E-Rare website. A second transnational call for proposals is being planned for early 2009.
Other International News
FDA consumer update addresses successes of the Orphan Drug Act
As the United States celebrates 25 years of the Orphan Drug Act, the US Food and Drug Administration has issued a consumer update highlighting the accomplishments that have taken place in the field of orphan medicinal products for rare disorders in the past 25 years. Designed for consumers, the document explains what an orphan drug is and how the implementation of the Orphan Drug Act in 1983 has helped usher many treatments through research and to the marketplace. To date, more than 1700 drugs and biologics have received orphan drug designation in the US. In 1990, the US introduced the Humanitarian Device Exemption (HDE), allowing a medical device to be approved if it is proved safe and beneficial for patients with extremely rare conditions (fewer than 4000 Americans each year). Over 120 medical devices have received designation as humanitarian use devices - and more than forty of these have received HDE approval.
California bill requires insurers to cover rare metabolic disease nutritional treatment
In California, the Evans Bill has been passed by the state assembly and is now before the Senate undergoing further review. Sponsored by the March of Dimes, the bill requires insurers and health plans to cover the costs of screening and treatment for inborn errors of metabolism (IEM) in newborns. California's newborn screening programme tests all newborns for 47 different IEMs, in addition to four endocrine and 24 haemoglobin disorders. But under current law, treatment coverage is only obligatory for one IEM: phenylketonuria. The bill would require that the special food and nutrient products needed to treat IEM be covered by all private insurers and health plans in the state. Early diagnosis and treatment would ultimately save over $140 million per year. Currently, only 39% of privately-insured Californians have coverage for IEM medical nutritional therapy. Low-income residents receiving state disbursed coverage are fully reimbursed for such products.

Ethical, Legal & Social Issues
The EMEA releases ethical considerations for paediatric clinical trials
The European Community regulation 1901/2006 (the Paediatric Regulation) that came into force in January 2007 as a means of ensuring medicinal products are safe and effective for children will lead to an increase in clinical trials in this vulnerable population. The European Medicines Agency (EMEA) has made available a set of recommendations concerning ethical aspects of clinical trials involving children in order to enhance a harmonised approach across the EU to conducting clinical trials on paediatric populations. Approval of a clinical trial, including any ethical aspect, is currently performed at the national level. Ethical considerations for clinical trials on medicinal products conducted with the paediatric population were developed by the ad hoc group for the development of implementing guidelines for Directive 2001/20/EC relating to good clinical practice in the conduct of clinical trials on medicinal products for human use, chaired by the European Commission. Issues covered include informed consent and the necessity to inform and involve children in decision-making as much as possible in an age-appropriate manner. The recommendations also discuss the composition of an ethics committee in respect to a paediatric clinical trial; the design of a paediatric clinical trial, including the use of placebos and control groups; and guidelines for minimising pain, distress, and fear. Risk/benefit ratios, unnecessary replication of trials, adverse effect reporting, compensation, and insurance are other topics broached.
Consult the Ethical Considerations document


EU Project Follow-up
Treat-NMD develops «toolkit» for creating registries
The EU FP6-funded Network of Excellence Treat-NMD (contract nr LSHM-CT-2006-036825), a consortium of 21 pan-European partner organisations focusing on neuromuscular disorders, is dedicated to encouraging the development of registries for specific rare diseases in individual countries and throughout Europe. Well-constructed registries provide an effective method of tracking prevalence and incidence for a particular disorder and can contribute to cultivating and harmonising good practices for diagnostics, treatment and care. Treat-NMD has prepared a toolkit intended to guide development applicable either for countries that have not yet developed registries or for a particular disease that is to date unregistered. The information is geared to creating registries that will ultimately be able to join the Treat-NMD global registry. As such, certain criteria must be included and the Treat-NMD registries charter must be adhered to. The toolkit offers guidance on issues such as developing and working within a legal and ethical framework, data protection, patient information and consent, and professional involvement. The Treat-NMD global registry will run on the Universal Mutation Database (UMD) software, devised specifically for capturing information concerning genetic mutations. This software is freely available. Details can be found at the UMD website. The Treat-NMD toolkit could potentially serve as a guide for any rare disease patient group or professional interested in developing a registry for a particular disease.

Orphanet News
Retailored Orphanet website launches
Orphanet, the European portal for rare disease and orphan drug information, unveiled its revamped website on 17 March. Talk about new and improved! The remodeled website is a customised portal geared to furnish a wealth of information and services all available from the site’s homepage. As was reported in the last issue of OrphaNews Europe, the Orphanet database of rare diseases and orphan drugs has been enhanced with new information, including prevalence, onset, mode of inheritance and genetics.

The updated website now has a classification scheme that categorises and cross-references any given disease by scientific, medical and genetic criteria, enabling professionals to access information from a generic category, and improving data capture instrumental to future policy making and fund distribution decisions and treatment development in both the public and private sectors. The revision of the Orphanet website was two years in the making, but the general consensus so far is that it has definitely been worth the wait!
New Texts
New Orphanet Journal of Rare Diseases publications
Hereditary sensory neuropathy type I

New Genes
Dwarfism and microcephaly: pericentrin mutations at cause
Two research teams have published studies identifying mutations in the gene encoding pericentrin, a centrosome structural protein, in patients with two similar disorders: Seckel syndrome and microcephalic osteodysplastic primordial dwarfism type II. Both disorders are characterised by dwarfism and microcephaly. Furthermore, the authors report that cells of individuals with Seckel syndrome due to these mutations have defects in ATR-dependent checkpoint signalling, providing the first evidence linking a structural centrosomal protein with DNA damage signalling.
Read the first PubMed abstract
Read the second PubMed abstract

Nature Genetics ; 232-236 ; February 2008
Science ; 816-819 ; February 2008

Lethal motoneuron syndrome type 1: mutations affect mRNA export mediator
Lethal motoneuron syndrome type 1 is an autosomal recessive disease characterised by marked atrophy of the spinal cord and total immobility of the foetus, detectable from the thirteenth week of pregnancy. The authors report that the defective gene underlying the disease is the mRNA export mediator GLE1. This finding elucidates mRNA processing as a critical molecular mechanism in motoneuron development and maturation.
Read the PubMed abstract

Nature Genetics ; 155-157 ; February 2008
MELAS syndrome: the cytochrome c oxidase subunit II gene is mutated
MELAS (Myopathy, Encephalopathy, Lactic Acidosis, and Stroke-like episodes) is a progressive neurodegenerative disorder characterised by acute neurological episodes resembling strokes associated with hyperlactatemia and mitochondrial myopathy. It is caused by mutations in the mitochondrial tRNA genes and mitochondrial-encoded subunits of respiratory complex I. The authors of this study have identified a single nucleotide deletion in the gene of subunit II of cytochrome c oxidase. The lack of subunit II precludes the assembly of cytochrome c oxidase and leads to the degradation of unassembled subunits, even those not directly affected by the mutation.
Read the PubMed abstract

Journal of Medical Genetics ; 117-121 ; February 2008

Research in Action
Fundamental Research
Autosomal dominant optic atrophy: oxygen reactive species may contribute to the pathogenesis
Mutations in optic atrophy 1 (OPA1), a nuclear gene encoding a mitochondrial protein, is the most common cause for autosomal dominant optic atrophy (DOA). The condition is characterised by gradual loss of vision, colour vision defects, and temporal optic pallor. The authors studied the role of OPA1 in Drosophila. They showed that mutations of the orthologue gene induced apoptosis during eye development and augmented the production of oxygen reactive species in the adult fly. This could indicate antioxidant agents as potential therapeutic agents.
Read the PubMed abstract

PLoS Genet ; e6 ; January 2008
Clinical Research
Merkel cell carcinoma: a new virus participates in the pathogenesis
Merkel cell carcinoma is a rare but aggressive human skin cancer that typically affects elderly and immunosuppressed individuals, a feature suggestive of an infectious origin. The researchers have identified a new virus that is present in 80% of Merkel cell carcinoma tumours versus 8% of unaffected tissues. This new virus may thus contribute to the pathogenesis of the carcinoma.
Read the PubMed abstract

Science ; Epub ahead of print ; January 2008
Amyotrophic lateral sclerosis: a susceptibility factor identified
Amyotrophic lateral sclerosis (ALS) is a degenerative disease of the nervous system caused by a progressive loss of motor neurons leading to increasing motor difficulties. The authors have identified a SNP in DPP6 gene that is strongly associated with susceptibility to ALS. The study was conducted on 1767 cases and 1916 healthy controls. DPP6 encodes a peptidase expressed predominantly in the brain. The finding is the first report of a genome-wide significant association with sporadic ALS and may be a target for future functional studies.
Read the PubMed abstract

Nature Genetics ; 29-31 ; January 2008
Kawasaki disease: a functional variant of ITPKC predisposes to the disease
Kawasaki disease is a paediatric systemic vasculitis of unknown aetiology for which a genetic influence is suspected. The authors identified a functional variant of gene ITPKC strongly linked to the disease and to an elevated risk of coronary artery lesions in children. ITPKC is a negative regulator of T cell activation. According to the authors, the susceptibility variant could contribute to the immune hyper-reactivity observed in Kawasaki disease.
Read the PubMed abstract

Nature Genetics ; 35-42 ; January 2008
Uniparental disomies of chromosome 14: a correlation between gene expression in 14q32.2 region and patient phenotype
Uniparental disomies of chromosome 14 present distinct phenotypes according to their origin – paternal or maternal. In the first instance, patients present facial dysmorphia, a small, bell-shaped thorax, abdominal wall defects, and polyhydramnios. In the second instance, patients present pre-and post-natal growth retardation, and precocious puberty. The authors studied 8 patients with a paternal disomy and three with a maternal disomy. Having identified different deletions and epimutations affecting the imprinted region, they were able to establish a correlation between the phenotype observed in each of the two disomies and the regulation of expression of certain genes on chromosome 14.
Read the PubMed abstract

Nature Genetics ; 237-242 ; February 2008
Atypical hemolytic uremic syndrome: some children develop Factor H autoantibodies
Atypical hemolytic uremic syndrome is a severe renal disease that is associated with defective complement regulation caused by multiple factors. Deficiency of factor H-related proteins CFHR1 and CFHR3 is a predisposing factor. The authors identify in an extended cohort of 147 patients that 16 juvenile individuals (ie, 11%) who either lacked CFHR1/CFHR3 completely or showed extremely low CFHR1/CFHR3 plasma levels are positive for factor H autoantibodies. Screening for both factors is obviously relevant for these patients as reduction of CFH autoantibody levels represents a therapeutic option.
Read the PubMed abstract

Blood ; 1512-1514 ; February 2008
Hereditary diabetes type 2: age at diagnosis varies according to the type and position of HNF1A mutations
Certain forms of hereditary diabetes type 2, also known as MODY (maturity-onset diabetes of the young) can be caused by mutations in gene HNF1A. The authors observed that diabetes is diagnosed earlier in patients carrying truncating mutations than in patients with missense mutations. Additionally, the age of diagnosis varies according to the location of mutations in the gene.
Read the PubMed abstract

Diabetes ; 503-508 ; February 2008
ICF Syndrome: early diagnosis improves course of disease
Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome) is a rare autosomal recessive disease characterised by facial dysmorphism, immunoglobulin deficiency and branching of chromosomes 1, 9 and 16 after PHA stimulation of lymphocytes. The authors analysed the phenotype spectrum of 45 patients, confirming that facial dysmorphism and hypo- or agammaglobulinaemia is present in almost all patients. Early diagnosis of ICF is important since early introduction of immunoglobulin supplementation can improve the course of the disease.
Read the PubMed abstract

Journal of Medical Genetics ; 93-99 ; February 2008
Acromegaly: increased risk of death confirmed
Acromegaly is a disease marked by hypertrophy of the extremities and gigantism caused by excessive secretion of growth hormone (or somatotrophin) by the pituitary. To date, no study has statistically confirmed an increased risk of mortality in patients. The authors conducted a meta-analysis comprising 16 studies, revealing that mortality is increased for these patients, even after transsphenoidal surgery. Long-term exposure to growth hormone could be a factor contributing to mortality. This study underscores the importance of early diagnosis in order to improve treatment approach.
Read the PubMed abstract

J Clin Endocrinol Metab ; 61-67 ; January 2008
Therapeutic Approaches
Osteogenesis imperfecta: cellular therapy proves efficacy in mice
Osteogenesis imperfecta is characterised by osteopenia and skeletal fragility due to an abnormal production of collagen by the osteoblasts. Current treatment is empirical. The authors transplanted human first-trimester fetal blood mesenchymal stem cells into homozygous oim mice in utero. They observed a reduction of fractures by two-thirds as well as a reduction of skeletal anomalies.
Read the PubMed abstract

Blood ; 1717-1725 ; February 2008
Diagnostic Approaches
Analysis of dysmorphic faces aided by various aspects of computer technology
Digital image analysis of faces has been demonstrated to be effective in a small number of syndromes. In this paper, the authors investigate several aspects that help bring these methods closer to clinical application. They conclude that including side-views increases accuracy, as does the use of geometry.
Read the PubMed abstract

Eur J Med Genet ; 44-53 ; January/February 2008

Patient Management and Therapy
Aplastic anaemia: better survival with stem cell transplantation versus second immunosuppressive therapy in refractory children
Aplastic anaemia is the incapacity of the bone marrow to replace red blood cells normally as they mature. Two possible treatments exist to date: stem cell transplantation using a family member with a compatible HLA system, or when this is not possible, immunosuppressive treatment. In this prospective study, the authors compared stem cell treatment with repeated immunosuppressive therapy on children who failed to respond to an initial course of treatment. At 5 years from the initiation of second-line therapy, the estimated failure-free survival (FFS), defined as survival with response, was 83.9% in the stem cell transplanted group compared with 9.5% in the immunosuppressive therapy group.
Read the PubMed abstract

Blood ; 1054-1059 ; February 2008
Chronic immune thrombocytopenic purpura: romiplostim has long-term benefits
Chronic immune thrombocytopenic purpura (ITP) is characterised by accelerated platelet destruction and decreased platelet production. Short-term administration of the thrombopoiesis-stimulating protein, romiplostim, has been shown to increase platelet counts in most patients with chronic ITP. The authors assessed the long-term administration of romiplostim in splenectomised and non-splenectomised patients with ITP during a twenty-four week period. Romiplostim was well tolerated, and increased and maintained platelet counts in splenectomised and non-splenectomised patients with ITP. Many patients were able to reduce or discontinue other ITP medications.
Read the PubMed abstract

The Lancet ; 395-403 ; February 2008
Chronic inflammatory demyelinating polyradiculoneuropathy: immunoglobulin treatment shows long-term efficacy
Chronic inflammatory demyelinating polyradiculoneuropathy is a progressive neuropathy that is most likely auto-immune in origin. Preliminary studies suggest that the intravenous administration of immunoglobulins reduces the disability of the disease in the short-term. 117 patients were included in a double-blind placebo study lasting an initial 24 week period that was doubled for patients showing improvement. Results demonstrated the short- and long-term efficacy and safety of the intravenous administration of immunoglobulins.
Read the PubMed abstract

Lancet Neurol ; 136-144 ; February 2008
Recurrent PTEN-deficient glioblastoma: rapamycin shows anticancer activity
Glioblastomas are malignant cerebral astrocytic tumours. Studies have shown that the loss of PTEN protein expression improves tumour response to rapamycin. In a phase I clinical trial, the authors tested rapamycin in patients presenting a glioblastoma not expressing PTEN. They observed an anticancerous action. This early study underlines the importance of monitoring target inhibition and negative feedback to guide future clinical development.
Read the PubMed abstract

PLoS Med ; e8 ; January 2008
Methylmalonic and propionic aciduria: carglumic acid lowers plasma ammonia levels
Hyperammonemia in patients with methylmalonic aciduria and propionic aciduria is caused by accumulation of propionyl-CoA which decreases the synthesis of N-acetyl-glutamate. The authors of this study tested carglumic acid in two patients. The treatment with carglumic acid decreased high plasma ammonia levels.
Read the article

Orphanet J Rare Diseases ; 3(1):2 ; January 2008
Brucellosis: treatment and recommendations
Brucellosis is a disease transmissible from animals to humans, caused by Brucella bacteria. In November 2006, an international colloquium led to the development of new recommendations based on information in the literature. Experts find the optimum treatment for non complex forms of the disease should be based on administration of doxycycline for six weeks in combination with streptomycin for two or three weeks.
Read the PubMed abstract

PLoS Med ; e317 ; December 2007

Orphan Drugs
FDA approves an Interleukin-1 blocker for familial cold auto-inflammatory syndrome and Muckle-Wells syndrome
The U.S. Food and Drug Administration has approved Arcalyst (rilonacept), an Interleukin-1 blocker for the long-term treatment of familial cold auto-inflammatory syndrome (FCAS) and Muckle-Wells syndrome (MWS). Arcalyst relieves symptoms of these disorders, including joint pain, rash or skin lesions, fever and chills, eye redness or pain, and fatigue. Interleukin-1 acts as a messenger to regulate inflammatory responses, but in excess can be harmful and has been shown to be key in the inflammation seen in FCAS or MWS patients.
For more information


News from the Patients' Associations
On the 3Oth anniversary of Swedish pioneer group PIO, the group's chair describes the development of the PID patient group
OrphaNews Europe presents the history of a Swedish patient organisation that this year celebrates 30 years of effort to support primary immunodeficiency disease patients and their families. The Primary Immunodeficiency Organisation (PIO) was created in 1978 - the first patient organisation in its field. Below PIO chair Anneli Larsson describes the creation and growth of the organisation:

The Primary Immunodeficiency Organisation (PIO) was founded in 1978 by a Swedish mother who lost her three children to a primary (congenital) immunodeficiency disease (PID). PIO, established by Maj Lis Hellström, was the first organisation in the world for PID patients. At the time of its development, there was no treatment available for the most severe condition, severe combined immunodeficiency (SCID). Today, the majority of children with this disease are saved via stem cell transplantation. Affected children must, however, be diagnosed early and transplanted during their first year of life - preferably within the first few months - in order to have a fair chance.

The most common form of PID is a lack of gammaglobulin. PID patients are vulnerable to an increased number of infections. A common cough can lead to complications such as sinusitis and pneumonia. There are many variants of PID - about 130 different syndromes have so far been defined by the WHO. It is imperative that treatment be given early to prevent permanent organ damage. Nonprofit research group the Jeffrey Modell Foundation (JMF) has developed a list of the primary warning signs of PID, published here with permission from the JMF and the International Patient Organisation for Primary Immunodeficiencies (IPOPI).

Treatment varies according to the type of PID. Those that are caused by a lack of gammaglobulin are commonly treated by infusion of gammaglobulin from healthy donors. In the most severe forms of PID, stem cell transplantations are carried out. There are also PIDs that can be treated with various signalling substances (cytokines) to stimulate the development of granolucytes. Many primary immunodeficiencies require long and repeated treatment with antibiotics.

Information - a challenge
Over the years, PIO has carried out extensive work in the field of information. Thirty years ago there was little information available to the public and even most general practitioners had never heard of PID. Today there is excellent information available through different sources, such as the patient organisations. In Sweden, the National Board of Health and Welfare provides good material on rare disorders, including some of the PID disorders. Despite the enormous efforts made to provide information to doctors, there are still many patients who have not been properly diagnosed. PIDs are considered rare diseases, yet it has been estimated that the real prevalence in the European Union may be as high as 1 in 250-500. This figure was presented during an EU PID conference in 2006 arranged by the IPOPI. (Consult the findings of this conference).

International cooperation
At an early stage, PIO recognised the importance of international cooperation and took an active part in the creation of NMPI, the Nordic Meeting of Primary Immunodeficiencies, as well as IPOPI. On an international level, IPOPI encourages and supports the creation of new patient organisations and today there are organisations in over 20 countries around the world. When a disease is rare it is important to find ways to cooperate between countries to gain knowledge and experiences from a larger population.

Advances in research
During the thirty years that PIO has been in existence, a lot has advanced in the care and treatment of PID diseases. Since 1983, PIO has given financial support annually to various research projects concerning primary immunodeficiencies. These research grants are made possible by donations to the organisation. The financial support we can offer is minor as we do not have the resources to give more. But PIO also supports research in practice and encourages members to participate in studies that are of interest to our group.

Cooperation with doctors and nurses
PIO has enjoyed a positive and fruitful cooperation with doctors and nurses treating PID patients. This cooperation includes medical advice and an exchange of experiences from the different perspectives each group has on PID. In 2006, guidelines for the diagnosis and treatment of a number of PID diseases were established by a group of doctors working with PID. PIO supports these guidelines and participated in their production by offering comments on the contents.

A large number of PIO members took part in a Swedish study named ALPI (Living with Primary Immunodeficiency), which is probably the largest study of its kind ever to have been carried out in terms of the number of patients involved. It was drawn up by a research group consisting of ten nurses with the aim to investigate the living situation of patients and parents and quality of life in relation to the disease. This study was finished and presented in 2007.

Increase of members
PIO experiences a steady increase of new members, which is not very common for organisations today. PIO started in 1978 with 25 members. Today we have almost 900 (the last five years have seen an increase of 360 members). I believe that one reason for the increase is that we value the heart and soul of our organisation. We acknowledge that as an organisation we are one strong voice with more power to influence decisions concerning our group within healthcare and in the society.

Day-to-day work
PIO works on raising political awareness, supporting patients and their families, and organising education/training and family camps in order to improve the situation for PID patients. We work to improve early diagnosis, decrease the number of unrecorded cases, and to provide patients with the possibility to take part in society as equals. This work tends to be more and more political. At the same time, it is important to focus on the members and to offer them opportunities to learn more about their condition and to exchange knowledge and experiences.

Since 2001 PIO has arranged annual family camps for children up to age 15 with PID as well as their families. These camps are rewarding for the whole family and are very much appreciated. The camps have been held at the same site that offers various outdoor activities and a peaceful surrounding for the children, their siblings and parents to meet others in the same situation and to learn more about PID. During the weekend, lectures are given separately to the children and to parents from doctors or psychologists or dieticians, etc. Last year we arranged the first youth camp for members aged 16-25 in connection with the family camp. These youth camps will also become an annual event.

PIO’s annual meetings have, since the start, introduced interesting speakers. Over the years, a wide range of subjects have been covered, such as the latest research in the field, basic knowledge on PIDs, coping strategies, legal rights, nutrition and much more. Every second year, the annual meeting lasts for two days in order to give more time for lectures and personal encounters between members.

PIO also supports members in starting regional groups. These groups offer a closer relationship between members in the area, and can organise more frequent meetings. They are also important because they permit more direct contact with the health care services and politicians in their region and can influence on a local level. A training day is arranged annually for the representatives from the regional groups.

A place for comfort
There have been ups and downs in the history of PIO. The organisation went through a tragic period in the 1990s when life-saving gammaglobulin was infected with Hepatitis C. A number of members were infected and some died within a few years. In an organisation like PIO there are many losses. In difficult times, you realise the importance of an organisation like ours in providing knowledge, information, and serving as the forum that speaks up for patients with PID. Last but not least, it is a place to find comfort by sharing with others.

Looking to the future
This month we are arranging a three-day anniversary meeting packed with a wide variety of lectures and what we hope will be a pleasant social programme. This event will include the participation of all the Nordic countries. Meanwhile, PIO is prepared to meet the challenge of helping PID patients and their families for another 30 years - the unrecorded cases must be found, and patients need to be diagnosed earlier. We must continue, as an organisation, to be a strong voice protecting PID patients’ interests wherever they appear. We will also bear in mind our very important role in bringing people together and offering opportunities to exchange knowledge and experiences. Contact PIO


Courses & Educational Initiatives
European School of Genetic Medicine: 21st Course in Medical Genetics
Taking place from 4-10 May, 2008, in Bertinoro di Romagna, Italy, themes include an introduction to contemporary genetic analysis, genetics and diseases, clinical genetics and population variation, mitochondrial medicine, different approaches to therapy for genetic disorders and immunogenetics, and human variation and complex disorders.
For further information and to register

European School of Genetic Medicine: 2nd Course in Clinical Dysmorphology
Taking place from 11-14 May, 2008 in Bertinoro di Romagna, Italy, the second course in clinical dysmorphology includes a series of topics including: what dysmorphic features can tell us about early developmental pathology; the development and uses of a new standardized terminology for the evaluation of dysmorphic patients; determination of dysmorphic features: the use of measurements; twinning and congenital developmental defects; teratology; neural crest and neural tube; limb birth defects; bone development; and understanding the relationship of genotypes to phenotypes.
For further details and to register

Second Annual Introductory Course on Skeletal Dysplasias
This course, taking place from 7-11 July 2008 at the Centre for Pediatrics and Adolescent Medicine in Freiburg, Germany, is intended to provide an introduction to the basic clinical and radiographic diagnostics and clinical management of skeletal dysplasias. The number of participants is limited to 10. The official language is English.
For further information


What's on Where?
Fifth International Congress on FMF and Systemic Autoinflammatory Diseases
Date: 4-8 April 2008
Venue: Rome, Italy

This conference will review current knowledge of the mechanisms of innate immunity and their relevance to the pathogenesis of autoinflammatory and other chronic diseases.
For further details

19th Conference of the German Society of Human Genetics
Date: 8-10 April 2008
Venue: Hannover, Germany

This year the main focus will be on the following subjects: Genetic origins of pain intensity, connective tissue disorders and complex infectious diseases; New therapeutic approaches to genetic diseases; The role of miRNAs and epigenetic modification; Proteomics; The structure of human genetic health care services in Europe.
For further details

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.
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.
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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

Genetic Alliance Annual Conference 2008
Date: 11-13 July 2008
Venue: Bethesda, MD, US

Brings advocates, health professionals, policy makers, industry representatives, researchers, and community leaders together for workshops and discussions.
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

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


Press & Publications
New assay for Fragile X put to the test
Fragile X syndrome presents one of the most common requests for genetic testing. In the UK, the Clinical Molecular Genetics Society audit for 2006/2007 recorded over 10,500 postnatal Fragile X reports issued across UK labs - comprising 13.6% of all postnatal molecular genetic testing reports, a number second only to cystic fibrosis. A significant proportion of these reports are only issued after carrying out Southern blot analysis as PCR analysis is inconclusive in homozygous normal female samples and large expansions cannot be detected by standard PCR methods. Abbott Molecular recently released a PCR-based analyte specific reagent kit for Fragile X diagnosis. The Manchester-based National Genetics Reference Laboratory conducted a study involving thirteen different laboratories in order to evaluate this new kit. The results have now been published in an assessment report. According to the authors, the new Abbott kit offers a certain number of advantages in terms of robustness, rapid detection of a high proportion of large expansions and reliable determination of heterozygosity in female heterozygotes with one repeat differences, but is unlikely to significantly reduce the burden of Southern analysis, as the assay does not reliably determine zygosity of female samples with a single allele in the normal range.
Read the assessment report

The 2008 Contact a Family Directory provides resource information across the UK
The new edition of the Contact A Family Directory, due out in April, contains over 350 entries covering more than 900 rare disorders "from Abdominal Exstrophies to Xeroderma Pigmentosum". This leading source of information on rare disorders provides a brief medical description of each condition, including patterns of inheritance and screening availability, and lists support group information, publications, regional genetic centres, hospices and other related organisations across the UK. First published in 1991, the Contact a Family Directory is now in its 17th revision. Contact a Family maintains a database of conditions in addition to those listed in the directory. The directory is available in print, CD and online versions. The group has also published a Rare Eye Conditions Directory, covering over 60 rare eye disorders.

Orphanews Europe, the newsletter of the European Union Committee of Experts on Rare Diseases
Orphanews Europe is supported by the European Commission's DG SANCO
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
Contact Us
Editorial Board: Ségolène Aymé, Kate Bushby, Catherine Berens, Helena Kaariainen, Yann Le Cam, Jordi Llinares-Garcia, Antoni Montserrat, Catherine Pouzat, Charlotte Rodwell, Christophe Roeland

EUCERD Country Representatives: Helmut Hintner (Austria), Pol Gerits (Belgium), Radka Tincheva (Bulgaria), Ivo Baric (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek Jr. (Czech Republic), Marianne Jespersen (Denmark), Inna Vabamae (Estonia), Helena Kaariainen (Finland), Alain Garcia (France), Birgit Schnieders (Germany), Christos Katamis (Greece), Janos Sandor (Hungary), Sveinn Magnusson (Iceland), John Devlin (Ireland), Bruno Dallapiccola (Italy), Antra Valdmane (Latvia), Jonas Bartlingas (Lithuania), Yolande Wagener (Luxembourg), Maria-Louise Borg (Malta), Harry Seeverens (Netherlands), Stein Are Aksnes (Norway), Jakub Adamski (Poland), Luis Nunes (Portugal), Ana Maria Vladareanu (Romania), Borut Peterlin (Slovenia), Frantisek Cisareik (Slovak Republic), Isabel Pena-Rey (Spain), Michael Soop (Sweden), Sabina Gallati (Switzerland), Edmund Jessop (UK)
EUCERD ECDC Representative: Andrew Amato
EUCERD Patient Organisation Representatives: Dorica Dan, Torben Gronnebaek, Yann Le Cam, Christel Nourissier
EUCERD Pharmaceutical Industry Representatives: Wills Hughes-Wilson, Kevin William Loth, Samantha Parker, Barbara Valenta
EUCERD Rare Disease Projects under Health Programmes Representatives: Ségolène Aymé, Jean Donadieu, Dian Donnai, Laura Fregonese, Ester Garne, Domenica Taruscio, Joan Luis Vives Corrons, Thomas Wagner, Susan Webb
EUCERD Rare Diseases Research Projects under Framework Programmes for Research and Technological Development Representatives: Jean-Yves Blay, Kate Bushby, Marc de Baets, Olaf Hiort, Sophie Koutouzov, Gerard Wagemaker
EUCERD European Commission Participants: Catherine Berens, Jordi Llinares-Garcia (EMA), Georgios Margetidis, Antoni Montserrat Moliner, Christophe Roeland, Stefan Schreck, Kerstin Westermark (EMA-COMP)
Orphanet Partner Country Representatives: Tamara F. Sarkisian (Armenia), Yvonne Zurynski (Australia), Till Voigtlander (Austria), Herwig Jansen (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), John Rosendahl Ostergaard (Denmark), Vallo Tillmann (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann-Spangenberg (Germany), Michael Petersen (Greece), Sandor Janos (Hungary), Andrew Green (Ireland) Lina Basel (Israel), Bruno Dallapiccola (Italy), Tomoko Kodama (Japan), Jana Lepiksone (Latvia), André Mégarbane (Lebanon), Viadutis Kucinskas (Lithuania), Yolande Wagener (Luxembourg), Abdelaziz Sefiani (Morocco), Gert-Jan van Ommen (Netherlands), Stein Are Aksnes (Norway), Malgorzata Krajewska-Walasek (Poland), Jorge Sequieros (Portugal), Cristina Rusu (Romania), Dragica Radojkovic (Serbia), Laszlo Kovacs (Slovakia), Borut Peterlin (Slovenia), Francesc Palau (Spain), Desirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Ugur Ozbek (Turkey), Dian Donnai (UK)
For more information on the European Union Committee of Experts on Rare Diseases
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