19 December 2007 print
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Editorial
 

What a year it has been!

 

2007 has been a year of action and movement. Policy makers, patient organisations, scientists and industry have all done their share to ensure concrete solutions are being made available on behalf of rare disease patients across Europe. The most exciting of these is probably the Communication on European Action in the Field of Rare Diseases, now open for Public Consultation. Rare Diseases: Europe's Challenges will serve as a rich source for defining priorities and informing decisions for rare disease strategies in the present and future European Member State health policy programmes. OrphaNews Europe once again emphasises the importance of your response to this document, now available in all EU languages. If you haven't already done so, please take the time to review the Communication and offer feedback in the language of your choice. Your contributions will be published and made available to Members of Parliament, including those from your country.

Other achievements of the year include actions on the part of many Member States: Romania, Portugal, Italy, Spain and Greece are all busy creating a national plan for rare diseases, while Bulgaria, Ireland, Netherlands, Sweden, and Slovenia are discussing how to proceed in this arena. Denmark has just formed its first national rare diseases committee; Spain has created a major scientific cooperative for rare disease research (CIBERER) and is working to gain official recognition for genetic medicine; Italy has established a rare disease council; France created an additional 29 centres of reference for rare diseases, and continues to establish reimbursement policies that relieve the financial burden of rare diseases. France also held its annual Telethon, bringing awareness to the issues rare disease patients face while at the same time raising over 100 million euros in much needed funds. Meanwhile, Luxembourg produced a first study of its rare disease patients, with a view to creating policies to ease their burden; and Switzerland adopted orphan medicine legislation similar to EU regulations. Germany has decided to relaunch a call for funding for rare disease research networks. Belgium created a new rare disease website, while Hungary formed a national alliance for rare diseases this year. In the United Kingdom, regional and national initiatives in the areas of genetic research, rare disease diagnostics and paediatric clinical studies got off the ground in 2007.

At the European level, several conferences were hosted to further define priorities for rare disease policy and funding. Grant schemes continue to offer hope for rare disease research with new revenues available via FP7 for 2007-2013. This funding translates directly into innumerable advances in the areas of fundamental, clinical, gene, and treatment research.

The EC Rare Diseases Task Force held a number of important workshops and meetings and continues to move forward in a variety of arenas. Notably, the Coding and Classification working group is collaborating with the World Health Organization to make rare diseases more visible in the International Classification of Diseases. The Standards of Care working group is gearing up to assess the added value of European networks of centres of reference.

Genetic testing also saw some major progress with quality assurance standards being defined and implemented across Europe and other parts of the world. The OECD published its guidelines this year in order to ensure quality in molecular genetic testing throughout both OECD and non-OECD countries.

In terms of information, Orphanet, the free-access European portal for rare disease information, has been working hard to revamp its entire website. The new version will be available in six languages in early 2008 and features many exciting new services, such as the capacity to search diseases by signs or symptoms, and updates in many areas, including the disease and orphan drug databases. The new user-friendly version will also feature a gene link for each disease where available and offers a quality assessment for European genetic laboratories, provided by an expanding collaboration with EuroGentest.

Finally, the EMEA and the pharmaceutical industry made concrete contributions toward furnishing medicinal products for rare disease patients. Seventy-seven products received orphan designations this year. Thirteen new orphan medicines were granted marketing authorisations in Europe. The EMEA has formed a partnership with the FDA in the US to facilitate orphan drug application procedures in both regions.

Can 2008 sustain this momentum? 29 February - a day that occurs only once every four years - has appropriately enough been chosen as European Rare Diseases Day. The National Rare Disease Alliances of several EU countries, in partnership with Eurordis, have worked on this latest initiative to bring public attention and support to rare disease patients and their families. The slogan chosen this year will be A Rare Day for Very Special People and the theme is to be Rare Disease: A Public Health Priority, coinciding with the EC Communication on Rare Diseases. Other non-European countries are also considering adopting the day, which will take place on 28 February during the years that do not have a 29 February.

Subscriptions to OrphaNews Europe have surpassed 10,000. We welcome this year's new subscribers and wish all our readers a holiday season filled with joy. We look forward to collaborating with you in the new year to keep all rare disease actions and initiatives in perpetual motion.



 


 
EU Policy News
 
EC issues Communication for the 2008-2009 disabled persons action plan
 
The European Commission has published a Communication directed toward the European Council, Parliament, Economic and Social Committee, and Committee of the Regions. The Situation of disabled people in the European Union: the European Action Plan 2008-2009 takes stock of the circumstances and statistics of disabled European Union citizens and seeks to measure the impact of the EU Disability Plan 2003-2010, as well as define priorities for 2008-2009. The majority of Member States identify their disabled citizens, those affected physically and/or mentally, as amongst the most disadvantaged members of society. Exclusion from employment opportunities is a major concern for this population and thus a leading priority for the action plan. Inclusion cannot happen without improved accessibility. Removing physical blocks that restrict active participation in the labour market and access to goods, services and infrastructures is a concrete action to be taken on both the national and European levels. Newly created annual meetings of European disability ministers are expected to strengthen Europe's strategy in this arena. Read the Communication
 


 
National & International Policy Developments
 
Denmark forms national rare diseases committee
 
A national committee for rare diseases has been formed in Denmark. The initiative came from members of umbrella organisation Sjaeldne Diagnoser, representing 35 patient organisations in the field of rare diseases, as well as members from the Center for Small Handicap Groups, the Kennedy Center, various clinics for rare diseases and handicaps in Copenhagen and Aarhus, and Kraeftens Bekaempelse (the Cancer Society). The committee's goal is to increase awareness of rare disease patients and their needs in Denmark and to establish a national strategy.
 
Other European news
 
UK alliance helps genetic disorder patients get fair access to life insurance
 
In the United Kingdom, life insurance products are intended to provide financial security to families after the death of the subscriber. However, patients with genetic disorders often have trouble obtaining equitable access to these products. The alliance organisation Genetic Interest Group (GIG) has established a pilot project to help address this issue. One of the main obstacles for both patients and insurance companies is a lack of prior knowledge of the patient's condition. This results in long, costly investigations in order to determine if granting insurance is feasible. Collaborating with patient support groups (including Gaucher disease and multiple endocrine neoplasia disorder type 2), insurance underwriters and medical professionals, GIG developed a template document that could accompany a life insurance application. The templates contain general information on the condition, including prognosis and potential complications, as well as specific information concerning the applicant. The template must be signed by both the patient and the patient's health professional. These two-page documents were tested on insurance companies - a process that yielded some useful feedback. GIG is now seeking endorsement for the templates from the Association of British Insurers and is preparing to carry out the next phase of the project: extending the templates to other forms of insurance, such as travel and critical care.
 
HON to be France's official accrediting body for health internet information
 
The Health On the Net Foundation (HON) is a non-profit, non-governmental leading organisation for the promotion and guidance of useful, reliable, appropriately used online medical and health information. Now, France has named HON as the official accrediting organisation for all its websites. The French National Health Authority (HAS) has chosen HON to certify its country's health websites via the implementation of the HONcode - a set of eight quality criteria. HON collaborates with the World Health Organization and is accredited to the Economic and Social Council of the United Nations. Orphanet, including OrphaNews Europe, already enjoys HON accreditation.
 
Other International News
 
First rare disease compassionate allowance hearing held in the US
 
In the US, the Social Security Administration held its first Compassionate Allowance Outreach Hearing on Rare Diseases in early December. The Compassionate Allowances initiative is designed to facilitate the rapid extension of benefits to applicants with conditions that obviously meet disability standards. There is currently a large backlog of applications - some years old. The Hearing was held to obtain public opinion on implementing Compassionate Allowances for children and adults suffering from rare disorders. In the US, a disease is considered rare if it affects less than 200,000 members of the country's population. The Hearing consisted of testimonies from various stakeholders in the field, including law and government policy experts, representatives from an array of rare disease foundations, scientists and academics. Until the issue is resolved, some patient group representatives are advising families to list symptoms on their benefit applications rather than the disease name itself. Many Social Security agents are unfamiliar with a majority of the 7000-plus rare diseases - a problem that slows, if not completely thwarts, the benefits approval process for these patients. Read the panel member testimonies.
 
Childhood cancer mortality drops in US
 
A report published this month from the US Centers for Disease Control and Prevention cites a decline in childhood cancer mortality from 34.2% in 1990 to 27.3% in 2004. All childhood cancers are rare diseases. The majority of childhood cancer deaths were caused by leukaemia and brain and other CNS malignancies. Of these, leukaemia had the most significant reduction in mortality rates. While drops in mortality rates were similar for children and adolescents regardless of age group or gender, discrepancies were found between racial and ethnic groups and between geographic locations. The report attributes the decline in mortality to the availability of better treatments. Indeed, several orphan oncology medicinal products have been brought to market in recent years in both the US and Europe. View the list of available orphan oncology drugs.
 


 
Orphanet News
 
New Texts
 
New Orphanet Journal of Rare Diseases publications
 
Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome

 
New Research Projects open for Recruitment
 
A Phase II Trial With Bevacizumab and Irinotecan for Patients With Primary Brain Tumors and Progression After Standard Therapy (in Denmark)

A Phase II Trial With Cetuximab, Bevacizumab and Irinotecan for Patients With Malignant Glioblastomas and Progression After Radiation Therapy and Temozolomide (in Denmark)


 


 
New Syndromes
 
A new syndrome of intractable diarrhea and choanal atresia/stenosis
 
The authors describe three siblings with a syndrome of intractable diarrhea of infancy and choanal atresia/stenosis. These children also have small stature, a prominent and broad nasal bridge, micrognathia, single palmar creases, chronic corneal inflammation, episodic cytopenia, and abnormal hair texture. They present normal intelligence and do not have immune deficiency, distinguishing this syndrome from others previously described.
Read the PubMed abstract

 
Clin Dysmorphol ; 211-221 ; October 2007
 


 
New Genes
 
Fried syndrome: AP1S2 mutations in two families
 
Fried syndrome is characterised by an X-linked mental retardation, mild facial dysmorphism, calcifications of basal ganglia and hydrocephalus. A large four-generation family in which the affected males have striking clinical features of Fried syndrome were investigated for linkage to X-chromosome markers; the results showed that the gene for this condition lies within the Xp22 region. In total, 60 candidate genes located in this region, including AP1S2, which was recently shown to be involved in mental retardation, were screened for mutations. A mutation in the third intron of AP1S2 was found in all affected male subjects in this large French family. The mutation resulted in skipping of exon 3, predicting a protein with three novel amino-acids and with termination at codon 64. In addition, the first known large Scottish family affected by Fried syndrome was reinvestigated, and a new nonsense mutation was found in exon 3.
Read the PubMed abstract

 
Journal of Medical Genetics ; 739-744 ; November 2007
 
Emery-Dreifuss muscular dystrophy has two new genes implicated
 
Emery-Dreifuss muscular dystrophy (EDMD) is a heterogeneous late-onset disease involving skeletal muscle wasting and heart defects caused, in a minority of cases, by mutations in either of two genes encoding the inner nuclear membrane (INM) proteins, emerin and lamins A/C. The authors investigated the presence of anomalies in the genes encoding nesprin 1 and 2 in 190 patients. Nesprin-1 and -2 are multi-isomeric, spectrin-repeat proteins that bind both emerin and lamins A/C and form a network in muscle linking the nucleoskeleton to the INM. They also identified four heterozygous missense mutations in these genes, associated with morphological anomalies of the nuclear membrane in the cells of these patients.
Read the PubMed abstract

 
Human Molecular Genetics ; 2816-2833 ; December 2007
 
Waardenburg syndrome type 2 has mutations in SOX10 gene
 
Waardenburg syndrome (WS) is an auditory-pigmentary disorder that exhibits varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. Depending on additional symptoms, WS is classified into four subtypes, WS1-WS4. Absence of additional features characterises WS2. The association of facial dysmorphic features defines WS1 and WS3, whereas the association with Hirschsprung disease (aganglionic megacolon) characterises WS4. Mutations within the gene SOX10 have been observed in patients with WS4. Now, the authors have identified SOX10 gene deletions in patients with type 2 of the syndrome. Neurological phenotypes reminiscent of that observed in WS4 were observed in some WS2-affected patients with SOX10 deletions. This study further characterises the molecular complexity and the close relationship that links the different subtypes of WS.
Read the PubMed abstract

 
American Journal of Human Genetics ; 1169-1185 ; December 2007
 
Oto-dental syndrome has FGF3 haploinsufficiency, plus FADD deletion in ocular forms
 
Oto-dental syndrome, a rare but severe autosomal-dominant craniofacial anomaly, is characterised by grossly enlarged molars and with a high-frequency sensorineural hearing loss. In three families, the authors linked the transmission of the disease to the presence of heterozygous microdeletions in chromosome region 11q13. The smallest of these deletions measures 43 kb and contains a sole gene: FGF3. Moreover, the patients in one family presented ocular coloboma associated with the transmission of a FADD gene deletion.
Read the PubMed abstract

 
Human Molecular Genetics ; 3482-3493 ; October 2007
 


 
Research in Action
 
Fundamental Research
 
Myotonic dystrophy 1: DMPK protein is essential to muscle insulin action
 
Myotonic dystrophy 1 is caused by CTG expansion in the 3' untranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. Patients present with a resistance to insulin, amongst other characteristics. DMPK-deficient mice exhibit impaired insulin signalling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. The reduction of DMPK expression in patients would thus be at least partly the cause for insulin resistance. The authors also suggest that this molecular mechanism is implicated in type 2 diabetes, making DMPK a new candidate gene for this common disease.
Read the PubMed abstract

 
PLoS ONE ; e1134 ; November 2007
 
Clinical Research
 
Juvenile polyposis syndrome: increased risk of polyposis and gastric cancer in patients with SMAD4 mutations
 
Juvenile polyposis syndrome is a dominant autosomal disease characterised by the childhood appearance of multiple polyps in the stomach, small intestine, colon and rectum. Some 40% of cases are due to point mutations or insertions or deletions in the genes SMAD4 (20%) and BMPR1A (20%). In this study, the authors identified point mutations in one of these two genes in 46% of patients and deletions of the entire gene or several exons in 14% of patients. Patients carrying SMAD4 also present increased risk of gastric polyposis (73% versus 8% of BMPR1A gene mutation carriers). Moreover, all gastric cancers were observed in carriers of SMAD4 gene mutations. Finally, about one-fourth of SMAD4 gene mutation carriers also present a hereditary hemorrhagic telangiectasia.
Read the PubMed abstract

 
Journal of Medical Genetics ; 702-709 ; November 2007
 
Germline CDH1 mutations in lobular breast cancer
 
The cell surface glycoprotein E-cadherin (CDH1) is a key regulator of adhesive properties in epithelial cells. The gene CDH1 is mutated in hereditary diffuse gastric cancers, patients of which have an increased risk of developing breast cancer. The authors analysed the sequence of this gene in 23 women presenting a hereditary form of breast cancer or having been diagnosed before the age of 45 years and not presenting mutations in genes BRCA1 or BRCA2. They identified a germline mutation in CDH1 in a woman presenting a hereditary form of breast cancer. Germline CDH1 mutations can thus be associated with invasive lobular breast cancer in the absence of diffuse gastric cancer.
Read the PubMed abstract

 
Journal of Medical Genetics ; 726-731 ; November 2007
 
Mucopolysaccharidosis type IIIA: natural history and evaluation of the disease progression
 
Mucopolysaccharidosis types IIIA through IIID (Sanfilippo syndrome) are lysosomal storage disorders caused by deficiencies of enzymes involved in the degradation of heparan sulfate. The onset and severity of the disease are highly variable. The authors used a detailed questionnaire and scoring system method to describe the natural course of mucopolysaccharidosis type IIIA in a cohort of 71 patients. On average, first symptoms were observed from age 7 months and diagnosis was made at four and a half years. Motor development and language delays were observed in 33.9% and 66.2% of patients respectively. Motor and cognitive regression begins typically at age 3.3 years. The 4-point scoring system may be used to classify patients into groups with a rapid or slower course of the disease. This may have an important impact on parental counselling as well as therapeutic interventions.
Read the PubMed abstract

 
Pediatrics ; e1255-e1261 ; November 2007
 
Wegener granulomatosis: ANCA levels cannot be used to guide immunosuppressive therapy
 
Wegener granulomatosis is a necrotizing vasculitis associating inflammation of the vessel wall and peri- and extra-vascular granulomatosis. Diagnosis depends upon the combination of clinical signs and the detection of antineutrophil cytoplasmic antibodies (ANCA). The authors enrolled 156 patients in order to measure whether anti-pro-proteinase 3 (PR3)-ANCA levels are a better measure of disease activity than anti-mature-PR3-ANCA levels, whether decreases in either level are associated with shorter time to remission, and whether increases are followed by relapse. They concluded that anti-pro-PR3-ANCA is no better than anti-mature-PR3-ANCA as a measure of Wegener granulomatosis activity; decreases in anti-PR3-ANCA levels are not associated with shorter time to remission, and increases are not associated with relapse. These findings suggest that ANCA levels cannot be used to guide immunosuppressive therapy.
Read the PubMed abstract

 
Ann Intern Med ; 611-619 ; November 2007
 
Gene Therapy
 
Mucopolysaccharidosis type IIIA mice show functional improvement following double gene therapy
 
Mucopolysaccharidosis type IIIA is a lysosomal storage disorder caused by the congenital deficiency of sulfamidase. The authors administered sulfamidase and the protein SUMF1 via gene therapy to disease model mice. They observed a synergistic effect on the enzyme activity, leading notably to an improvement in cognitive and motor function.
Read the PubMed abstract

 
Human Molecular Genetics ; 2693-2702 ; November 2007
 
Therapeutic Approaches
 
Cystic fibrosis: furin inhibitors may represent a therapeutic strategy
 
Cystic fibrosis (CF) is characterised by alterations in the CFTR protein, the most well documented function of which is the regulation of transmembrane hydroelectrolytic flux. Alterations in the protein lead to changes in the characteristics of exocrine excretions. One of the principal causes of morbidity stems from chronic pulmonary pyocyanic infections. The authors measured activity of the major endoprotease furin and demonstrated a marked upregulation in human CF cells. Increased furin activity was linked to elevated production in CF of the immunosuppressive and tissue remodeling cytokine TGF-beta and its downstream effects, including macrophage deactivation and augmented collagen secretion by epithelial cells. As furin is responsible for the proteolytic processing of a range of endogenous and exogenous substrates including growth factors and bacterial toxins, the authors determined that elevated furin-dependent activation of bacterial exotoxin A caused increased cell death in CF respiratory epithelial cells compared with genetically matched CF transmembrane conductance regulator-corrected cells. Thus elevated furin levels in CF respiratory epithelial cells contribute to bacterial toxin-induced cell death, fibrosis, and local immunosuppression. These data suggest that the use of furin inhibitors may represent a strategy for pharmacotherapy in CF.
Read the PubMed abstract

 
Journal of Clinical Investigation ; 3489-3497 ; November 2007
 
VLCAD deficiency: the potential of bezafibrate
 
Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an inborn mitochondrial fatty-acid beta-oxidation (FAO) defect associated with a broad mutational spectrum, with phenotypes ranging from fatal cardiopathy in infancy to adolescent-onset myopathy, and for which there is no established treatment. Recent data suggest that bezafibrate could improve the FAO capacities in beta-oxidation-deficient cells, by enhancing the residual level of mutant enzyme activity via stimulation of gene expression. Since VLCAD-deficient patients frequently harbor missense mutations with unpredictable effects on enzyme activity, we investigated the response to bezafibrate as a function of genotype in 33 VLCAD-deficient fibroblasts representing 45 different mutations. Treatment with bezafibrate (400 microM for 48 h) resulted in a marked increase in FAO capacities, often leading to restoration of normal values, for 21 genotypes that mainly corresponded to patients with the myopathic phenotype. In contrast, bezafibrate induced no changes in FAO for 11 genotypes corresponding to severe neonatal or infantile phenotypes. Altogether, the responses to bezafibrate reflected the severity of the metabolic blockage in various genotypes, which appeared to be correlated with the phenotype, thus providing a new approach for analysis of genetic heterogeneity.
Read the PubMed abstract

 
American Journal of Human Genetics ; 1133-1143 ; December 2007
 
Diagnostic Approaches
 
3-methylcrotonyl-coenzyme A carboxylase deficiency: measure for 3-methylcrotonylglycine could lead to misdiagnosis
 
3-methylcrotonyl-coenzyme A carboxylase deficiency is a metabolic disorder characterised by neurological symptoms including psychomotor delay, epileptic problems, cerebral atrophy and tetraplegia. Increased 3-methylcrotonylglycine level in the urine is a diagnostic marker of the disease. However, the authors of this study observed an absence of this amino acid in two children presenting the disorder. They suggest that residual enzymatic activity in these patients is responsible for the absence of raised 3-methylcrotonylglycine levels in the urine. This study reveals the potential risk for diagnostic error linked to this marker.
Read the PubMed abstract

 
Pediatrics ; e1335-e1340 ; November 2007
 
Glutaric acidemia type I: glutamate and GABA level spectroscopic measurement – a new diagnostic tool
 
Glutaric acidemia type I (GA-I) is an inherited disorder of lysine and tryptophan metabolism presenting with striatal lesions anatomically and symptomatically similar to Huntington disease. Affected children commonly suffer acute brain injury in the context of a catabolic state associated with nonspecific illness. Using a mouse model of GA-I, the authors showed that pathologic events began in the neuronal compartment while enhanced lysine accumulation in the immature brain allowed increased glutaric acid production resulting in age-dependent injury. Glutamate and GABA depletion correlated with brain glutaric acid accumulation and could be monitored in vivo by proton nuclear magnetic resonance (1H NMR) spectroscopy as a diagnostic tool. Blocking brain lysine uptake reduced glutaric acid levels and brain injury. These findings offer potential new monitoring and treatment strategies that may translate for use in human GA-I.
Read the PubMed abstract

 
Journal of Clinical Investigation ; 3258-3270 ; November 2007
 


 
Patient Management and Therapy
 
Schnitzler syndrome: antibiotics improve patient condition
 
Schnitzler syndrome is characterised by chronic urticarial rash and monoclonal IgM gammopathy and is sometimes associated with periodic fever, arthralgias, and bone pain. The authors report on eleven patients with Schnitzler syndrome treated with oral pefloxacin mesylate (800 mg/d). In 10 patients, a dramatic and sustained improvement of urticarial and systemic manifestations was observed. Corticosteroid therapy could be stopped or reduced in 6 patients. In 9 patients, pefloxacin was administered for more than 6 months with a good safety profile.
Read the PubMed abstract

 
Arch Dermatol ; 1046-1050 ; August 2007
 
Hematopoietic stem cell transplantation for immunodeficiency-centromeric instability-facial dysmorphism syndrome
 
Immunodeficiency-centromeric instability-facial dysmorphism syndrome is caused by epigenetic dysregulation resulting in hypomethylation. In many patients, mutations in DNMT3B, a DNA methyltransferase gene is the cause of the illness. Associated infections are a major cause of serious sequelae and death. The authors report three unrelated patients with persistent infections and intestinal complications who successfully underwent hematopoietic stem cell transplantation. In all cases, transplantation led to resolution of intestinal complications and infections, growth improvement, and correction of the immunodeficiency.
Read the PubMed abstract

 
Pediatrics ; e1341-e1344 ; November 2007
 
For Pompe disease, pilot studies are needed to assess appropriateness of a newborn screening strategy
 
Pompe disease is a lysosomal storage disorder that leads to the accumulation of glycogen and subsequently to muscle weakness, organ damage, and death. Pompe disease is detectable through newborn screening, and treatment has become available recently. The authors sought to review all available evidence regarding screening for infantile Pompe disease to help policy makers determine whether Pompe disease should be added to their state's newborn screening battery. They concluded that pilot studies are needed to identify the most efficacious strategy for screening and to determine how to manage cases of late-onset Pompe disease before screening for Pompe disease is adopted widely by newborn screening programs.
Read the PubMed abstract

 
Pediatrics ; e1327-e1334 ; November 2007
 
Polycythemia vera and essential thrombocythemia need specific paediatric diagnostic criteria
 
In the proposed revised World Health Organization (WHO) criteria for the diagnosis of BCR-ABL(-) myeloproliferative diseases (MPDs), exclusion criteria have been replaced by the presence of JAK2 mutations. The authors applied these criteria to 45 children with MPDs. They found that the JAK2(V617F) mutation in children occurs less frequently than in adults, and that exon 12 JAK2 mutations are absent. On the basis of the revised WHO criteria, a significant proportion of childhood polycythemia veras were misdiagnosed. Furthermore, all familial essential thrombocythemia, including patients carrying the hereditary MPL(S505N) activating mutation, were erroneously diagnosed as MPDs. These observations suggest that childhood MPDs require a set of specific diagnostic criteria.
Read the PubMed abstract

 
Blood ; 3384-3386 ; November 2007
 
Guidelines for molecular karyotyping in genetic diagnosis
 
Array-based whole genome investigation or molecular karyotyping enables the genome-wide detection of submicroscopic imbalances. Proof-of-principle experiments have demonstrated that molecular karyotyping outperforms conventional karyotyping with regard to detection of chromosomal imbalances. The authors demonstrated the benefits of using this technique for genetic diagnosis of developmental disorders. However, for use in prenatal diagnosis, more investigations are appropriate. This article also proposes a number of recommendations for optimising and standardising genetic test results between laboratories.
Read the PubMed abstract

 
Eur J Human Genetics ; 1105-1114 ; November 2007
 


 
Orphan Drugs
 
Five EMEA orphan drug designations for December
 

The COMP (Committee for Orphan Medicinal Products) adopted the following five positive opinions on orphan medicinal product designation at its December meeting for the treatment of:

- prevention of oral mucositis in head and neck cancer patients undergoing radiation therapy
- tuberculosis
- neuroblastoma
- gastro-entero-pancreatic neuroendocrine tumours
- acute myeloid leukaemia
Consult the European Registry for Orphan designations
Consult the Orphanet list of orphan drugs authorised for marketing in Europe

 
Orphan drug manufacturer selected as 2008 Technology Pioneer
 
The World Economic Forum has included Swiss orphan drug manufacturer mondoBIOTECH amongst its list of 39 visionary companies singled out as Technology Pioneers for 2008. The World Economic Forum defines itself as "an independent international organization committed to improving the state of the world by engaging leaders in partnerships to shape global, regional and industry agendas". To be selected as a Technology Pioneer, a company must "be involved in the development of life-changing technology innovation and have potential for long-term impact on business and society. In addition, it must demonstrate visionary leadership, show the signs of being a long-standing market leader - and its technology must be proven." MondoBIOTECH currently has five Orphan Designations in Europe, the latest one granted in October for the treatment of sarcoidosis. The Swiss company has 30 other products in development for 30 different indications. MondoBIOTECH is in good company - previous Technology Pioneers include companies such as Google and Napster.
 


 
Grants
 
Opening date for FDA orphan drug clinical study grants: 6 January 2008
 
The Food and Drug Administration (FDA) Office of Orphan Products Development (OOPD) has posted the opening date for the fiscal year 2009 grant awards to support clinical trials on the safety and effectiveness of products for rare diseases and conditions. An estimated $14 million in funds is available. Applications may be submitted to Grants.gov as of 6 January 2008. The application receipt date is 6 February, 2008. Grant-funded studies are intended to provide acceptable data to the FDA that will substantially contribute to the approval of new products, or new indications for already marketed products. In the FDA OOPD grants program, products for rare diseases and conditions (orphan products) are defined as drugs, biologics, medical devices, and medical foods indicated to treat or diagnose a rare disease or condition with a prevalence of fewer than 200,000 people in the United States.
For more details.

 


 
News from the Patients' Associations
 
New Duchenne website and registry unites patient and professional community
 
DuchenneConnect recently launched as a source for the Duchenne and Becker muscular dystrophy community to come together. DuchenneConnect provides diagnostic, care and treatment information and resources to patients, families, medical professionals, researchers, industry and policy makers. The site has a dual purpose, functioning as a source of information and also as a registry. When patients and families enter their medical information into the registry, they are automatically connected to the latest diagnostics and treatment information, as well as to families across the world who have also registered with DuchenneConnect. Medical and research professionals can also connect to the registry, using the data to advance understanding, treatment, and research for Duchenne and Becker muscular dystrophies. Finally, interested pharmaceutical companies can connect to the registry, using the data toward developing new medicines and treatments and to schedule new trials. All of these advances once again become available to registered patients and their families, and thus the chain of progress goes unbroken. DuchenneConnect was created by Parent Project Muscular Dystrophy (PPMD), the largest nonprofit organisation in the United States focussing entirely on Duchenne muscular dystrophy.
 


 
What's on Where?
 
4th International Symposium on the Biology and Immunology of Cutaneous Lymphomas
 
Date: 10-12 January 2008
Venue: Berlin, Germany

Sessions include tumour biology, genetics and mutations, new therapies, and classification and diagnosis.
More details

 
First International Symposium on Human Embryonic Stem Cell Research
 
Date: 31 January - 2 February 2008
Venue: Evry (Paris), France

International scientists will exchange ideas on human embryonic stem cell research. 29 lectures from selected specialists, including dedicated sessions for industrial applications of human ES cells and presentations of scientific networks supported by the European Commission.
More details and to register

 
EuroGentest Workshop: Towards Accreditation-Managing the Human Side of Change
 
Date: 7-8 February 2008
Venue: Nice, France

Within the context of introducing quality management leading toward accreditation, this workshop addresses overall insights into the 'human, behavioural' side of change with techniques to manage this part of the change process, using case studies and role play to help apply these insights and techniques to real life situations.
More details

 
Third Eastern European Conference on Rare Diseases and Orphan Drugs
 
Date: 1-2 March 2008
Venue: Plovdiv, Bulgaria

Participants from Bulgaria and Eastern Europe will present their achievements in the field of prevention, diagnosis and treatment of rare diseases. A specialized workshop with speakers from leading US, European and Bulgarian organisations and institutions will take place in order to discuss best practices in the field of rare diseases and orphan drug access.
More details and to register

 
Rare Diseases: Channels and Transporters
 
Date: 8-12 March 2008
Venue: Sant Feliu de Guixols, Spain

The conference is devoted to channels and transporters involved in rare inherited diseases. Specifically TRP and CLC channels, connexins, mitochondrial transporters, heteromeric amino acid transporters, neurotransmitter transporters, ABC transporters and related diseases will be covered.
For further details

 
Antwerp 2008 Conference on Quality in Medical Laboratories
 
Date: 10-11 March 2008
Venue: Antwerp, Belgium

The conference theme is Upgrade quality by using the proper metrics.
For further details

 
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

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

 
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. The deadline to submit an abstract for this conference is 4 February 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

 
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. The deadline for submitting abstracts for this conference is 30 November 2007.
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

 


 
Press & Publications
 
Market research report expects orphan drug market to grow 7% per year
 
According to a new technical market research report available for purchase, the global orphan drug market reached US$58.6 billion in 2006, up 8% from the previous year. It is expected to surpass US$80 billion by 2011. The US accounts for some 55% of the global market. Biologics comprise over 60% of all orphan drugs sold, and will continue to outpace non-biologics in coming years. Growth hormones and synthetics have the highest number of orphan drug approvals. The full report (PHM038B) is available at BCC Research and contains chapters on company profiles, trends in technology, legislation around the world, applications, products, global structure, and the history and overview of the orphan drug market.
 


 
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, Edmund Jessop, Matthieu Levi-Strauss, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Claire Scharf-Kroener, Janos Sandor, Arrigo Schieppati, Rumen Stefanov, Domenica Taruscio, Joan Luis Vives Corrons
For more information on the Rare Diseases Task Force
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