21 January 2009 print
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France starts 2009 with a resolution to create an even stronger national plan for rare diseases

Heralded as a model by countries throughout Europe and the world, the French National Plan for Rare Diseases underwent an audit earlier this month. The comprehensive scheme reached the end of its four-year term in December 2008. In October 2008, a collective sigh of relief was heard upon the announcement of French President Nicolas Sarkozy that the plan would be renewed following a period of appraisal and reprioritisation designed to enhance the optimisation of resources and services for the benefit of the Fifth Republic’s rare disease patients. The New Year celebrations had barely drawn to an end before French experts were gathering to review and analyse the achievements and bottlenecks of the ten-pronged plan and to start the debate over which elements to include in the new version, scheduled to appear in 2010. (Ongoing projects will continue to be funded through the one-year interim period of 2009). Of the plan’s ten strategic priorities, some elements have succeeded better than others. While some efforts moved forward to yield stunning results, a few initiatives barely got off the ground for a variety of reasons. The ten major priorities of the French plan are as follow:

1: Increase knowledge of the epidemiology of rare diseases
2: Recognise the specificity of rare diseases
3: Develop information for patients, health professionals and the general public concerning rare diseases
4: Train health professionals to better identify rare diseases
5: Organise screening and access to diagnostic tests
6: Improve access to treatment and the quality of patient care
7: Continue efforts in favour of orphan drugs
8: Respond to the specific accompaniment needs of people suffering from rare diseases
9: Promote research on rare diseases
10: Develop national and European partnerships

Of these ten elements, the third, centred on developing and disseminating information, has been one of the most successful. Two entities that have contributed to the efficacious distribution of information are i) the centres of reference that France has designated for specific rare diseases and ii) the informational services developed by Orphanet – of which the many services offered, including a database of over 5000 rare diseases available in five European languages, the creation of a nomenclature and medical/scientific classification for rare disorders is moving forward the process of establishing harmonisation between regions and countries. Other accomplishments of the French plan include the recognition of the profession of genetic counsellor fulfilled under the fourth priority and the designation of over 130 centres of reference for rare disorders under priority six, “Improve access to treatment and the quality of patient care”. Priority seven, “Continue efforts in favour of orphan drugs” has been achieved due in part to the forward-thinking reimbursement policies France has established that guarantee equity to its rare disease patients. The ninth priority, “Promote research on rare diseases” has also enjoyed strong results. The sums invested in fundamental and clinical research have doubled in France. Amongst the areas that didn’t get very far, under priority one, "Increase knowledge of the epidemiology of rare diseases", the committee to designate rare disease registries was established late in the game, resulting in the designation of only six rare disease registries by the end of the term of the plan. Priority two “Recognise the specificity of rare diseases” saw the development of some 30 National Diagnosis and Treatment Protocols that have had positive consequences for patients (all products mentioned in these official guidelines are subject to reimbursement, including non-medical products such as nutritional supplements and special creams), but with over 6000 recognised rare diseases, there is clearly some distance yet to go. Other points that did not get out of the starting gate include priority five: “Organise screening and access to diagnostic tests” and priority eight: “Respond to the specific accompaniment needs of people suffering from rare diseases” – although other initiatives within the French government are meeting some of these objectives. The next step will be the release of a report from the Public Health Council, based on the findings of an official evaluation committee and other key players, due out in March 2009. In the meantime, a French-language website created by the evaluation committee is available from which to monitor the ongoing assessment process.

Spotlight on...
Medicinal products for rare diseases in Turkey
In November 2008, Turkish pharmacist Pelin Kilic joined the team of Orphanet France in order to pursue her PhD studies in gene technology, specifically in the area of rare diseases, under the scope of a national government scholarship programme offered by the Turkish Ministry of Health. Ms. Kilic officially holds a position at the Turkish Ministry of Health Directorate General of Pharmaceuticals and Pharmacy, which she will resume upon her return to Turkey. Recently, she described for OrphaNews Europe the current situation of patient access to orphan medicinal products in Turkey:

OrphaNews Europe: How are orphan medicinal products categorised in Turkey?

Pelin Kilic: At present, the Turkish Ministry of Health (MOH) has not yet developed a national policy with reference to “rare diseases” and “orphan drugs”, as commonly defined inside the European Union (EU). Therefore, patients suffering from known rare diseases in Turkey access treatment with nationally licensed or non-licensed human medicinal products that have been granted marketing authorization (MA) by the European Medicines Agency (EMEA) under “orphan designation” and/or indicated for the treatment of specific rare diseases.

OrphaNews Europe: Could you comment on the regulation(s) under which medicinal products are registered in Turkey?

Pelin Kilic: In Turkey, licensing applications for all human medicinal products are submitted, by accredited license holders, to the Directorate General of Pharmaceuticals and Pharmacy (DGPP) operating under the MOH, in line with the “Regulation on Licensing for Medicinal Products for Human Use” (I shall hereafter refer to it as the “Regulation”).

OrphaNews Europe: How much compliance does Turkish regulation hold with regard to the EU Legislation?

Pelin Kilic: The Turkish Regulation currently in force has been adapted by the DGPP in accordance with the European Commission (EC) Directive 2001/83/EC placed under the EU Legislation related to medicinal products for human use. It is also based on the national Law No. 1262 for Pharmaceutical and Medicinal Preparations along with these items:
i) Article 3(k) of the Basic Law No. 3359 for Medicinal Services,
ii) Article 8 of the Law No. 2857 on Blood and Blood Products, and
iii) Article 43 of the Ministerial Decree No. 181 governing the Organization and Responsibilities of the Turkish MOH.

OrphaNews Europe: What kind of scientific evaluation processes are implemented for licensing applications?

Pelin Kilic: During the scientific and technological evaluation periods of pre-licensing, licensing applications are passed through several phases of Advisory Committees for efficacy, reliability and quality assessments in approval, listed below:
  • Advisory Committee dedicated to the Technological and Pharmacological Evaluation of Human Medicinal Products
  • Advisory Committee dedicated to the Bioavailability and Bioequivalence Evaluation of Human Medicinal Products
  • Advisory Committee dedicated to the Evaluation of Human Medicinal Products
  • .
    Read the full interview with Pelin Kilic


    EU Policy News
    New report exposes the implications of pending EU directive restricting MRI use
    A report issued by the Institute of Physics in the UK entitled MRI and the Physical Agents (EMF) Directive seeks to “spur informed debate” on Directive 2004/40/EC, a measure that would restrict the use of magnetic resonance imaging (MRI) scanners in the European Union. MRI technology, available since the 1970s, is used in the diagnosis and monitoring of an array of diseases – both rare and common – including cancers, brain disease, and congenital foetal disorders, some of which can be evaluated prenatally with the assistance of MRI technology (the technology can also be used to guide certain prenatal interventions). A reported 20,000 MRI scanners are currently in use around the world. The pending directive (delayed until April 2012) seeks to limit occupational exposure to EMF with frequencies of up to 300 GHz, thus restricting “known short term adverse effects in the human body”. One of the report’s authors, however, cautions that “it is difficult to avoid the conclusion that a range of current and emerging MRI procedures would be rendered illegal by the directive. Some of these techniques simply cannot be performed in other ways, and in other cases the only possible option would expose both the patient and workers to ionising radiation.”
    Consult the Institute of Physics report
    Consult Directive 2004/40/EC

    Official report of French EU presidency mentions rare disease initiatives
    An official report summarising the actions taken during the six month period that France took the helm of the European Union has been released. France’s initiatives in the field of rare diseases are mentioned: The French Presidency was able to share its determination to continue working in favour of a Europe of patients, notably by a coordinated approach to rare diseases. The Commission’s proposal of a recommendation which appeared on 11 November should allow concerted work between the Member States to be carried out on the question in the future. Consult the Report of the French Presidency of the Council of the European Union

    National & International Policy Developments
    Regions of Canada are adopting strategies for reimbursing medicinal products for rare diseases
    The province of Alberta, Canada, last month announced a programme for rare disease pharmaceutical products. The Alberta Rare Diseases Drug Program is a new initiative that will reimburse Alberta residents for their rare disease treatments. The scheme requires users to pay premiums and “make co-payments consistent with their government-sponsored drug coverage”. The diseases currently eligible for coverage include Gaucher disease, Fabry Disease, MPS-I (Hurler/Hurler Scheie), Hunter syndrome and Pompe disease – all of which have treatments costing between C$250,000 - C$1million (€156,440 - €625,600) per year. The programme is expected to get underway in April 2009.
    National Human Genome Research Institute seeks feedback
    In the USA, the National Human Genome Research Institute (NHGRI) has engaged in a long-range planning process targeting the future of human genome research. Three white papers have been posted on the NHGRI website in order to facilitate debate on the following topics: diagnostics, preventive medicine, and pharmacogenomics; therapeutics; and education and community engagement. These white papers are available for viewing and comment. The process is organised in two phases. Phase 1, open through January 30, 2009, will collect community thoughts solely on the questions posed in the white papers, aimed at ensuring that the right questions are being asked. Once the questions are refined, Phase 2 will commence and collect community input, most likely from mid-February 2009 through mid-April 2009. Other white papers on other topics may be added as the process continues. To stimulate discussion, comments received will be anonymously posted for viewing.
    Other European news
    Spanish region opens first hospital unit dedicated specifically for rare diseases
    A hospital in the Alicante province in the Valenician Community of Spain has opened a unit devoted specifically to rare diseases. According to various news releases, more than 22,000 persons in the city of Alicante have a rare disorder and some 300,000 persons in the Valencian Community. Thus the Hospital General Universitario de Alicante (HGUA) in November opened the Unidad Multidisciplinar de Enfermedades de Baja Prevalencia (multidisciplinary unit for diseases of low prevalence) - the first of its kind in the region. FEDER, the Federación Española de Enfermedades Raras, is involved in the initiative, which offers integrated and accessible health services to rare disease patients.
    Other International News
    Documents from first African Society for Primary Immunodeficiencies conference now available online
    The very first Congress of the African Society for Primary Immunodeficiencies, organised in cooperation with the Moroccan Societies for Paediatrics and for Haematologies, took place in late October 2008. Topics on the agenda included primary immunodeficiencies (PIDS) in relation to cutaneous manifestations, pulmonary manifestations, the adult patient, lymphomas, nutrition, and vaccines. Papers and presentations from lectures have now been stored on the African Society for Primary Immunodeficiencies website and are available for viewing (in French language).

    EU Project Follow-up
    Will man’s best friend fetch some clues to understanding monogenic diseases?

    LUPA, funded under the Seventh Research Framework Programme of the European Commission, is examining canine genetic conditions as a means to understanding more about human diseases – including rare disorders. Partners from 12 European countries will be collecting 10,000 DNA samples and genome wide association (GWA) data from purebred dogs that are either healthy or suffering from diseases that also affect humans. Work package five of the LUPA project could prove especially interesting to the rare disease community. The “Monogenic disease” work package will be examining several rare conditions. One working group will focus on “Exocrine Pancreatic Insufficiency”, a secondary condition in cystic fibrosis and Shwachmann-Diamond Syndrome. Meanwhile, the “Primary Ciliary Diskinesis” working group hopes that through analyzing dog pedigrees, identification of novel genes may be found for conditions such as Bardet-Biedl, Alstrom, Meckel-Gruber and Kartagener syndromes. The “Copper-associated diseases” (Wilson disease and Menkes disease) will study laborador retrievers, who have a high prevalence worldwide of copper-associated disorders. It is hoped that by learning more about these diseases in the dogs, new routes for treating copper storage diseases will be sniffed out.


    Orphanet News
    New Texts
    New Orphanet Journal of Rare Diseases Publications
    Progressive familial intrahepatic cholestasis
    Treacher Collins syndrome: etiology, pathogenesis and prevention (published in the European Journal of Human Genetics, in association with Orphanet)


    New Syndromes
    A new autosomal recessive syndrome with severe intellectual deficit, cataract, coloboma and kyphosis
    The authors report three siblings with a novel intellectual deficit syndrome, born to distantly related Iranian parents. The clinical manifestations comprise severe intellectual deficit, cataracts with onset in late adolescence, kyphosis, contractures of large joints, bulbous nose with broad nasal bridge, and thick lips. Two patients also had uni- or bi-lateral iris coloboma. Linkage analysis revealed a single 10.4 Mb interval of homozygosity with significant LOD score in the pericentromeric region of chromosome 4.
    Read the PubMed abstract

    European Journal of Human Genetics ; 125-128 ; January 2009

    New Genes
    Lethal congenital myopathy: mutations in a neural adhesion protein cause a familial form of the disease
    The authors report on four individuals from a consanguineous Egyptian family with a lethal congenital myopathy inherited in an autosomal-recessive fashion and characterised by a secondary loss of beta2-syntrophin and alpha-dystrobrevin from the muscle sarcolemma, central nervous system involvement, and foetal akinesia. Homozygosity mapping and candidate gene analysis identified a mutation in CNTN1, the gene encoding the neural immunoglobulin family adhesion molecule, contactin-1. The authors propose that loss of contactin-1 impairs communication or adhesion between nerve and muscle resulting in the severe myopathic phenotype.
    Read the PubMed abstract

    To read more about "Congenital myopathy"

    Am J Hum Genet ; 714-724 ; December 2008
    Iminoglycinuria and hyperglycinuria are discrete phenotypes resulting from mutations in proline and glycine transporters
    Iminoglycinuria (IG) is an autosomal recessive abnormality of renal transport of glycine and the imino acids proline and hydroxyproline. The related disorder hyperglycinuria (HG) without iminoaciduria has been attributed to heterozygosity of a putative defective glycine, proline, and hydroxyproline transporter, but confirming the underlying genetic defect(s) has been difficult. Here the authors applied a candidate gene sequencing approach in 7 families first identified through newborn IG screening programs. Both inheritance and functional studies identified the gene encoding the proton amino acid transporter SLC36A2 as the major gene responsible for IG in these families, and its inheritance was consistent with a classical semidominant pattern in which 2 inherited nonfunctional alleles conferred the IG phenotype, while 1 nonfunctional allele was sufficient to confer the HG phenotype. Mutations in SLC36A2 that retained residual transport activity resulted in the IG phenotype when combined with mutations in the gene encoding the imino acid transporter SLC6A20. Additional mutations were identified in the genes encoding the putative glycine transporter SLC6A18 and the neutral amino acid transporter SLC6A19 in families with either IG or HG, suggesting that mutations in the genes encoding these transporters may also contribute to these phenotypes.
    Read the PubMed abstract

    To read more about "Iminoglycinuria"

    J Clin Invest ; 3881-3892 ; December 2008
    Atypical hemolytic uremic syndrome: mutations in complement C3 predispose development of the disease
    Atypical hemolytic uremic syndrome (aHUS) is a disease of complement dysregulation. In approximately 50% of patients, mutations have been described in the genes encoding the complement regulators factor H, MCP, and factor I or the activator factor B. The authors report nine novel C3 mutations in 14 aHUS patients with a persistently low serum C3 level, establishing C3 as a susceptibility factor for aHUS.
    Read the PubMed abstract

    To read more about "Atypical hemolytic uremic syndrome"

    Blood ; 4948-4952 ; 15 December 2008
    Woodhouse-Sakati syndrome has mutations in C2orf37, encoding a nucleolar protein
    Hypogonadism, alopecia, diabetes mellitus, intellectual deficit, and extrapyramidal syndrome (also known as Woodhouse-Sakati syndrome) is a rare autosomal recessive multisystemic disorder. The authors have identified a founder mutation consisting of a single base-pair deletion in C2orf37 in eight families of Saudi origin. Three other loss-of-function mutations were subsequently discovered in patients of different ethnicities. The gene encodes a nucleolar protein of unknown function, and the cellular phenotype observed in patient lymphoblasts implicates a role for the nucleolus in the pathogenesis of this disease. These findings expand the list of human disorders linked to the nucleolus and further highlight the developmental and/or maintenance functions of this organelle.
    Read the PubMed abstract

    To read more about "Woodhouse-Sakati syndrome"

    Am J Hum Genet ; 684-691 ; December 2008
    Spastic paraplegia: a mutation in the acetyl-CoA transporter gene causes autosomal dominant form
    Hereditary spastic paraplegias (HSPs), characterised by progressive and bilateral spasticity of the legs, are usually caused by developmental failure or degeneration of motor axons in the corticospinal tract. There are considerable interfamilial and intrafamilial variations in age at onset and severity of spasticity. Genetic studies have also shown that there are dozens of genetic loci, on multiple chromosomes, that are responsible for HSPs. Through linkage study of a pedigree of HSP with autosomal-dominant inheritance, the authors mapped the causative gene to 3q24-q26. Screening of candidate genes revealed that the HSP is caused by a missense mutation in the gene for acetyl-CoA transporter (SLC33A1).
    Read the PubMed abstract

    Am J Hum Genet ; 752-759 ; December 2008
    Renal hypouricemia: mutations in glucose transporter gene at cause
    Renal hypouricemia is an inherited disorder characterised by impaired renal urate (uric acid) reabsorption and subsequent low serum urate levels, with severe complications such as exercise-induced acute renal failure and nephrolithiasis. The authors identified two loss-of-function heterozygous mutations in GLUT9, which occur in the highly conserved "sugar transport proteins signatures 1/2." Both mutations result in loss of positive charges, one of which is reported to be an important membrane topology determinant. The oocyte expression study revealed that both GLUT9 isoforms showed high urate transport activities, whereas the mutated GLUT9 isoforms markedly reduced them. These findings provide a physiological model of the renal urate reabsorption in which GLUT9 regulates serum urate levels in humans and can be a promising therapeutic target for gout and related cardiovascular diseases.
    Read the PubMed abstract

    To read more about "Hereditary renal hypouricemia"

    Am J Hum Genet ; 744-751 ; December 2008
    Diamond-Blackfan anaemia: ribosomal protein L5 and l11 mutations are associated with cleft palate and abnormal thumbs
    Diamond-Blackfan anaemia (DBA), a congenital bone-marrow-failure syndrome, is characterised by red blood cell aplasia, macrocytic anaemia, clinical heterogeneity, and increased risk of malignancy. Although anaemia is the most prominent feature of DBA, the disease is also characterised by growth retardation and congenital anomalies that are present in approximately 30%-50% of patients. The disease has been associated with mutations in four ribosomal protein (RP) genes, RPS19, RPS24, RPS17, and RPL35A, in about 30% of patients. However, the genetic basis of the remaining 70% of cases is still unknown. The authors report the second known mutation in RPS17 and probable pathogenic mutations in three more RP genes, RPL5, RPL11, and RPS7. In addition, they identified rare variants of unknown significance in three other genes, RPL36, RPS15, and RPS27A. Remarkably, careful review of the clinical data showed that mutations in RPL5 are associated with multiple physical abnormalities, including craniofacial, thumb, and heart anomalies, whereas isolated thumb malformations are predominantly present in patients carrying mutations in RPL11.
    Read the PubMed abstract

    To read more about "Blackfan-Diamond disease"

    Am J Hum Genet ; 769-780 ; December 2008
    Familial, nonsyndromic primary failure of tooth eruption has PTHR1 loss-of-function mutations
    Tooth eruption is a complex developmental process requiring coordinated navigation through alveolar bone and oral epithelium. Primary failure of tooth eruption (PFE) is associated with several syndromes primarily affecting skeletal development, but is also known as a nonsyndromic autosomal-dominant condition. Teeth in the posterior quadrants of the upper and lower jaw are preferentially affected and usually result in an open bite extending from anterior to posterior. In this study, the authors show that familial, nonsyndromic PFE is caused by heterozygous mutations in the gene encoding the G protein-coupled receptor for parathyroid hormone and parathyroid hormone-like hormone (PTHR1). Three distinct mutations were identified in 15 affected individuals from four multiplex pedigrees.
    Read the PubMed abstract

    Am J Hum Genet ; 781-786 ; December 2008
    Nonsyndromic deafness: mutations found in LRTOMT, a fusion gene with alternative reading frames
    Many proteins necessary for sound transduction have been identified through positional cloning of genes that cause deafness. The authors report here that mutations of LRTOMT are associated with profound nonsyndromic hearing loss at the DFNB63 locus on human chromosome 11q13.3-q13.4. LRTOMT has two alternative reading frames and encodes two different proteins.
    Read the PubMed abstract

    To read more about "Nonsyndromic genetic deafness"

    Nat Genet ; 1335-1340 ; November 2008
    ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy: TMEM70 mutations cause isolated forms
    The authors carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. These results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes.
    Read the PubMed abstract

    To read more about "NADH-CoQ reductase deficiency"

    Nat Genet ; 1288-1290 ; November 2008
    Lethal, infantile CI deficiency: a mitochondrial protein compendium elucidates disease biology
    Mitochondria are complex organelles whose dysfunction underlies a broad spectrum of human diseases. Identifying all the proteins resident in this organelle and understanding how they integrate into pathways represent major challenges in cell biology. Toward this goal, the authors performed mass spectrometry, GFP tagging, and machine learning to create a mitochondrial compendium of 1098 genes and their protein expression across 14 mouse tissues. They link poorly characterised proteins in this inventory to known mitochondrial pathways by virtue of shared evolutionary history. Using this approach, they predict 19 proteins to be important for the function of complex I (CI) of the electron transport chain. They validate a subset of these predictions using RNAi, including C8orf38, which harbours an inherited mutation in a lethal, infantile CI deficiency.
    Read the PubMed abstract

    To read more about "NADH-CoQ reductase deficiency"

    Cell ; 112-123 ; 11 July 2008

    Research in Action
    Fundamental Research
    Barth syndrome: cardiolipin provides an essential activating platform for caspase-8 on mitochondria
    Cardiolipin is a mitochondria-specific phospholipid known to be intimately involved with apoptosis. However, the lack of appropriate cellular models to date restricted analysis of its role in cell death. The maturation of cardiolipin requires the transacylase tafazzin, which is mutated in the human disorder Barth syndrome. Using Barth syndrome patient-derived cells and HeLa cells in which tafazzin was knocked down, the authors show that cardiolipin is required for apoptosis in the type II mitochondria-dependent response to Fas stimulation. Cardiolipin provides an anchor and activating platform for caspase-8 translocation to, and embedding in, the mitochondrial membrane, where it oligomerizes and is further activated, steps that are necessary for an efficient type II apoptotic response.
    Read the PubMed abstract

    To read more about "Barth syndrome"

    J Cell Biol ; 681-696 ; 17 November 2008
    Stevens-Johnson syndrome and toxic epidermal necrolysis: granulysin is a key mediator for disseminated keratinocyte death
    Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening adverse drug reactions characterised by massive epidermal necrosis, in which the specific danger signals involved remain unclear. Here the authors show that blister cells from skin lesions of SJS-TEN primarily consist of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, and both blister fluids and cells were cytotoxic. Gene expression profiling identified granulysin as the most highly expressed cytotoxic molecule, confirmed by quantitative PCR and immunohistochemistry.
    Read the PubMed abstract

    To read more about "Toxic epidermal necrolysis"

    Nat Med ; 1343-1350 ; December 2008
    Clinical Research
    Neuroblastoma task force develops global template for classifying risk
    Two articles in the December 2008 issue of the Journal of Clinical Oncology describe the work of the International Neuroblastoma Risk Group (INRG) task force classification system, created to establish a consensus approach for pre-treatment risk stratification. Neuroblastoma is a malignant tumour of neural crest cells. It is a childhood tumour occurring in infants and young children (90% of all cases involve children of 5 years of age or less) and accounts for 8 to 10% of paediatric cancers, affecting an estimated 11,000 children each year worldwide. It may arise at any site in the sympathetic nervous system, most commonly in the abdomen. Current approaches to risk classification and treatment stratification for children with neuroblastoma vary around the world, making it difficult to compare risk-based trials. The article entitled The International Neuroblastoma Risk Group (INRG) Classification System: An INRG Task Force Report analysed 13 prognostic factors in a cohort of 8800 children with neuroblastoma from Australia, Europe, Japan, and North America. Event-free survival was the primary end point. Stage, age, histologic category, grade of tumour differentiation, the status of the MYCN oncogene, chromosome 11q status, and DNA ploidy were cited as the most highly statistically significant and clinically relevant factors. A new staging system (the INRG Staging System) based on clinical criteria and tumour imaging was thus developed for the INRG Classification System. The second article, entitled The International Neuroblastoma Risk Group (INRG) Staging System: An INRG Task Force Report, describes the process of developing a new staging system using clinical criteria and image-defined risk factors. In order to establish the impact of the latter on outcome, a survival analysis of 661 European neuroblastoma patients with stage one, two or three of the disease was undertaken. Under the International Neuroblastoma Risk Group staging system (INRGSS), locoregional tumours are staged L1 or L2, based, respectively, on the absence or presence of one or more of 20 image-defined risk factors. Metastatic tumors are defined as stage M, except for stage MS, in which metastases are confined to the skin, liver, and/or bone marrow in children younger than 18 months of age. Within the 661-patient cohort, image-defined risk factors were present (ie, stage L2) in 21% of patients with stage 1, 45% of patients with stage 2, and 94% of patients with stage 3 disease. Patients with INRGSS stage L2 disease had significantly lower 5-year event-free survival than those with INRGSS stage L1 disease. The authors esteem that the use of the new staging (INRGSS) and risk classification (INRG) of neuroblastoma will greatly facilitate the comparison of risk-based clinical trials conducted in different regions of the world. The severity of neuroblastoma can differ widely, from mild to extremely aggressive. Thus, identifying the form is essential to administering the appropriate treatment.
    Lennox-Gastaut syndrome: a consensus approach on diagnosis, assessment, management, and trial methodology
    Lennox-Gastaut syndrome is one of the most severe epileptic encephalopathies of childhood onset. The cause of this syndrome can be symptomatic (ie, secondary to an underlying brain disorder) or cryptogenic (ie, has no known cause). Although Lennox-Gastaut syndrome is commonly characterised by a triad of signs, which include multiple seizure types, slow spike-wave complexes on electroencephalographic (EEG) recordings, and impairment of cognitive function, there is debate with regard to the precise limits, cause, and diagnosis of the syndrome. There are few effective treatment options for the multiple seizures and comorbidities, and the long-term outlook is poor for most patients. The authors discuss the main issues with regard to the diagnosis and treatment options available, suggest key considerations for future trials and highlight the importance of a comprehensive approach to the assessment and management of this syndrome.
    Read the PubMed abstract

    To read more about "Lennox-Gastaut syndrome"

    Lancet Neurol ; 82-93 ; January 2009
    Adenylosuccinate lyase deficiency and Angelman syndrome: similar behavioural phenotypes
    Adenylosuccinate lyase deficiency is a rare autosomal disorder of de novo purine synthesis, which results in the accumulation of succinylpurines in body fluids. Patients with adenylosuccinate lyase deficiency show a variable combination of intellectual deficit, epilepsy and autistic features and are usually discovered during screens for unexplained encephalopathy using the Bratton-Marshall assay that reveals the excretion of the succinylaminoimidazolecarboxamide riboside (SAICAr). The authors report on two sisters aged 11 and 12 years presenting with global developmental delay, motor apraxia, severe speech deficits, seizures and behavioural features, which combined excessive laughter, a very happy disposition, hyperactivity, a short attention span, the mouthing of objects, tantrums and stereotyped movements that gave a behavioural profile mimicking Angelman syndrome. Both patients had an increased succinyladenosine/SAICAr ratio of 1.6, and exhibited a novel homozygous missense mutation (c.674T>C; p.Met225Thr) in the exon 6 of the ADSL gene. On the basis of this observation, although adenylosuccinate lyase deficiency is a rare disorder, this diagnosis should be considered in patients with intellectual deficit and a behavioural profile suggestive of Angelman syndrome.
    Read the PubMed abstract

    To read more about "Adenylosuccinate lyase deficiency"
    To read more about "Angelman syndrome"

    Eur J Hum Genet ; 133-136 ; January 2009
    Behçet disease: prevalence study finds strong hereditary basis for the disease
    To estimate the prevalence of Behçet disease (BD) in a multiethnic population living in France, with particular focus on disease risk among immigrants, the authors conducted a study in a Paris metropolitan area with 1,094,412 adults of whom 26% are of non-European ancestry. Seventy-nine subjects fulfilled the search criteria. The overall prevalence per 100,000 adults was 7.1 and the prevalence for populations of European, North African, and Asian ancestry was 2.4, 34.6, and 17.5 respectively. The results suggest that BD risk is not related to age at immigration and support the hypothesis that BD has a primarily hereditary basis.
    Read the PubMed abstract

    To read more about "Behcet disease"

    Arthritis Rheum ; 3951-3959 ; December 2008
    Langerhans cell histiocytosis: incidence and clinical features in the UK and Ireland
    There are few published studies on epidemiology of Langerhans Cell Histiocytosis (LCH). The authors undertook a survey to ascertain all newly diagnosed cases aged 0-16 years in the UK and Republic of Ireland. Over a two-year period, 94 cases were identified. The age-standardised incidence rate of LCH in children aged 0-14 years was 4.1 per million per year. The sex ratio (M:F) was 1.5:1 and median age at diagnosis was 5.9 years. Single system disease (predominantly bony involvement) accounted for 73% cases and 27% had multi-system disease of whom 7% had involvement of "risk organs" (liver, lung, spleen, bone marrow). Three children died, two of whom were diagnosed post mortem. The incidence reported in this study is comparable with other national reports although it is likely to be underestimated as methods may have missed some cases, either diagnosed or undiagnosed.
    Read the PubMed abstract

    To read more about "Langerhans cell histiocytosis"

    Arch Dis Child ; Epub ahead of print ; 5 December 2008
    Squamous cell carcinoma of head and neck: A European epidemiologic perspective of human papillomavirus-related cases
    The aim of this study was to assess incidence and survival of human papillomavirus-related and unrelated head and neck squamous cell carcinoma sites from 15 European population-based cancer registries. This analysis was performed on 29,265 adult (aged approximately 15 years) cancer patients diagnosed in the period from 1988 to 2002. The human papillomavirus-unrelated cancer sites had an age-standardised incidence higher than the human papillomavirus-related cancer cases (3.8 versus 2.5/100,000 year). Incidence rates of head and neck squamous cell carcinomas increased more for human papillomavirus-related than unrelated cancer sites. Three-year survival rates improved more in human papillomavirus-related than unrelated cancer sites, and women had better rates of survival than men.
    Read the PubMed abstract

    To read more about "Squamous cell carcinoma of head and neck"

    Hematol Oncol Clin North Am ; 1143-1153 ; December 2008
    Cholangiocarcinoma: frequent questions answered concerning diagnostics and treatment
    Cholangiocarcinoma is an uncommon adenocarcinoma with poor prognosis. Although the 1-year survival has increased over time, the 5-year survival has not shown any significant change (less than 5%). Cure can only be expected from surgical resection of early stage tumours but most patients initially present with advanced disease. Cancer cachexia, liver failure, and recurrent sepsis due to biliary obstruction are among the main causes of mortality. Patient prognosis is strongly related to radical surgery and complete resection is the most effective therapy. Prognosis of cholangiocarcinoma remains poor even with aggressive surgical therapy because of the high incidence of local or regional recurrence and distant metastasis. Based on these data many questions need an answer: is there a role for adjuvant chemotherapy or radiotherapy? Would neoadjuvant treatments provide best results? Is there a standard therapy in unresectable or metastatic cholangiocarcinoma? This report tries to answer frequently asked questions (from diagnostic procedures to palliative treatment).
    Read the PubMed abstract

    To read more about "Cholangiocarcinoma"

    Crit Rev Oncol Hematol ; Epub ahead of print ; 31 October 2008
    Uveal melanoma: Patient survival in Europe
    Examining a large series of patients with uveal melanoma, the authors found that five-year relative survival remained stable with the introduction of conservative treatment in individuals in whom uveal melanoma was diagnosed between 1983 and 1994. Differences in survival were found between sexes and between European areas.
    Read the PubMed abstract

    Arch Ophthalmol ; 1413-1418 ; October 2008
    Fragile X syndrome: no evidence of neuropsychological findings among adult carriers of the FMR1 premutation
    The 5’ untranslated region of the fragile X intellectual deficit gene FMR1 contains a polymorphic CGG repeat. Expansions of this repeat are associated with a spectrum of disorders. Full mutation alleles, repeats >or= 200, are associated with fragile X syndrome. Premutation alleles, repeats of approximately 55-199, are associated with a tremor-ataxia syndrome most commonly in older males and primary ovarian insufficiency in females. However, the neuropsychological impact of carrying a premutation allele is presently unclear in younger adults. In this study, the authors analysed neuropsychological scores for 138 males and 506 females ascertained from the general population and from families with a history of fragile X syndrome. Subjects were age 18-50 years and had varying repeat lengths. Neuropsychological scores were obtained from measures of general intelligence, memory, and executive functioning, including attention. Among males, no repeat length associations were detected for any factor. Among females, premutation carriers self-reported significantly more attention-related problems compared to noncarriers. No significant interactions between repeat length and age were detected. Overall, these results indicate the lack of a global neuropsychological impact of carrying a premutation allele among adults under the age of 50.
    Read the PubMed abstract

    To read more about "Fragile X-associated with tremor/ataxia syndrome"

    Am J Hum Genet ; 692-702 ; December 2008
    Neurofibromatosis type 1-dependent tumours require a microenvironment containing Nf1+/-- and c-kit-dependent bone marrow
    Interactions between tumorigenic cells and their surrounding microenvironment are critical for tumor progression yet remain incompletely understood. Germline mutations in the NF1 tumour suppressor gene cause neurofibromatosis type 1 (NF1), a common genetic disorder characterised by complex tumours called neurofibromas. Genetic studies indicate that biallelic loss of Nf1 is required in the tumorigenic cell of origin in the embryonic Schwann cell lineage. However, in the physiologic state, Schwann cell loss of heterozygosity is not sufficient for neurofibroma formation and Nf1 haploinsufficiency in at least one additional nonneoplastic lineage is required for tumor progression. The authors establish that Nf1 heterozygosity of bone marrow-derived cells in the tumour microenvironment is sufficient to allow neurofibroma progression in the context of Schwann cell Nf1 deficiency. Further, genetic or pharmacologic attenuation of c-kit signaling in Nf1+/- hematopoietic cells diminishes neurofibroma initiation and progression.
    Read the PubMed abstract

    To read more about "Neurofibromatosis type 1"

    Cell ; 437-448 ; 31 October 2008
    Stem Cells
    Friedreich ataxia: cell functions impaired by frataxin deficiency are restored by drug-mediated iron relocation
    Various human disorders are associated with misdistribution of iron within or across cells. Friedreich ataxia (FRDA), a deficiency in the mitochondrial iron-chaperone frataxin, results in defective use of iron and its misdistribution between mitochondria and cytosol. The authors assessed the possibility of functionally correcting the cellular properties affected by frataxin deficiency with a siderophore capable of relocating iron and facilitating its metabolic use. Adding the chelator deferiprone at clinical concentrations to inducibly frataxin-deficient HEK-293 cells resulted in chelation of mitochondrial labile iron involved in oxidative stress and in reactivation of iron-depleted aconitase. The siderophore-like properties of deferiprone provide a rational basis for treating diseases of iron misdistribution, such as FRDA, anaemia of chronic disease, and X-linked sideroblastic anaemia with ataxia.
    Read the PubMed abstract

    To read more about "Friedreich ataxia"

    Blood ; 5219-5227 ; 15 December 2008
    Diagnostic Approaches
    Systemic-onset juvenile idiopathic arthritis: S100A12 is a novel marker that differentiates causes of fever of unknown origin
    Fever of unknown origin (FUO) in children presents a diagnostic challenge. The differential diagnosis includes systemic-onset juvenile idiopathic arthritis (JIA), an autoinflammatory syndrome associated with activation of phagocytic cells that, at presentation, is difficult to differentiate from severe systemic infections. This study investigated whether serum concentrations of the phagocytic proinflammatory protein S100A12 could help in deciding whether to treat patients with FUO with antibiotics or immunosuppressive agents. Serum samples were obtained from 45 healthy control subjects and from 240 patients (60 with systemic-onset JIA, 17 with familial Mediterranean fever [FMF], 18 with neonatal-onset multisystem inflammatory disease [NOMID], 17 with Muckle-Wells syndrome [MWS], 40 with acute lymphoblastic leukemia [ALL], 5 with acute myeloblastic leukemia [AML], and 83 with systemic infections). The sensitivity and specificity of S100A12 to distinguish between systemic-onset JIA and infections were 66% and 94%, respectively. S100A12, a marker of granulocyte activation, is highly overexpressed in patients with systemic-onset JIA or FMF, which may point to as-yet unknown common inflammatory mechanisms in these diseases. The measurement of S100A12 serum levels may provide a valuable diagnostic tool in the evaluation of FUO.
    Read the PubMed abstract

    To read more about "Arthritis, systemic-onset, juvenile idiopathic"

    Arthritis Rheum ; 3924-3931 ; December 2008

    Orphan Drugs
    EMEA starts the new year off with seven orphan drug designations in January

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

    - amyotrophic lateral sclerosis
    - betathalassaemia intermedia and major
    - acute myeloid leukaemia
    - acute lymphoblastic leukaemia
    - treatment of hypercortisolism (Cushing syndrome) of endogenous origin
    - mucopolysaccharidosis, type IVA (Morquio A Syndrome)
    - Pseudomonas aeruginosa lung infection in cystic fibrosis

    The COMP adopted one negative opinion recommending that the medicine 4-[[[4-(4-Chlorophenoxy)phenyl]sulfonyl]-methyl]tetrahydro-N-hydroxy-2H-pyran-4-carboxamide, from Anthony William Fox, for prevention of graft rejection after liver transplantation, not be granted designation as orphan medicinal product.
    Consult the European Registry for Orphan designations
    Consult the Orphanet list of orphan drugs authorised for marketing in Europe

    FDA approves imatinib mesylate to prevent recurrence of rare gastrointestinal cancer
    In the USA, the Food and Drug Administration has approved Gleevec (imatinib mesylate) for a new indication – keeping cancer from recurring in patients following surgical removal of a gastrointestinal stromal tumor (GIST). In a press release, Richard Pazdur, M.D., director, Office of Oncology Drug Products, Center for Drug Evaluation and Research, FDA, commented that the announcement of an approval of Gleevec for a new indication "illustrates how the continued study of a once novel drug throughout its product lifecycle can yield new and important uses." Gleevec, (marketed as Glivec in Europe) is manufactured by Novartis AG, Basel, Switzerland, and is approved for a total of nine different indications.
    Two medicinal product approvals, one withdrawal, and one extension of indication from the CHMP in December
    The Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion on initial marketing authorisation for Ixiaro (Japanese encephalitis vaccine, inactivated, adsorbed), from Intercell AG, for the active immunisation against Japanese encephalitis in adults. Ixaro is the 52nd orphan medicine to receive a positive opinion from the CHMP. EMEA review began on 30 January 2008 with an active review time of 204 days.

    The CHMP also adopted a positive opinion on initial marketing authorisation for Mepact (mifamurtide), from IDM Pharma S.A., for the treatment of non-metastatic osteosarcoma. Mepact is the 53rd orphan medicine to receive a positive opinion from the CHMP. EMEA review began on 22 November 2006 with an active review time of 205 days.

    The EMEA has been formally notified by Oncoscience AG of its decision to withdraw its application for an initial marketing authorisation for Theraloc (nimotuzumab), 5 mg/ml concentrate for solution for infusion. Theraloc was expected to be used to treat children and adolescents with resistant or recurrent high-grade glioma. Theraloc was designated as an orphan medicine on 2 September 2004. Read more about this decision

    The CHMP gave a positive opinion for extending the indication of previously-approved Zavesca (miglustat), from Actelion Registration Ltd, to extend the indication to the treatment of progressive neurological manifestations in adult patients and paediatric patients with Niemann-Pick type C disease. Zavesca is currently indicated for the oral treatment of mild to moderate type 1 Gaucher disease in patients for whom enzyme replacement therapy is unsuitable. Zavesca is an orphan-designated medicine.

    New article reviews policies encouraging orphan drug development in the USA
    An article appearing in the free-access Orphanet Journal of Rare Diseases reviews the various incentives established under the 1983 Orphan Drug Act in the United States to encourage the development of orphan drug products to treat rare disorders. The authors find that the grants, research design support, FDA fee waivers, tax incentives, and market exclusivity have all contributed to an increase in orphan drug approvals in the past 25 years, along with increased activity of the part of the National Institutes of Health, scientific advancements, and other drug and patent regulatory changes. New orphan molecules, however, have “a statistical significant less effective patent and market exclusivity life” than other new molecular entities. But new orphan molecules also experience “less generic competition” than other molecular entities.
    Consult the article Incentives for orphan drug research and development in the United States


    What's on Where?
    IBC Conference: Ushering in the New Era of Orphan Disease R&D, Clinical & Business Strategies
    Date: 5-6 February 2009
    Venue: Bethesda MD, USA

    Conference organiser IBC’s Inaugural Orphan Diseases conference will aim to deliver valuable information in a strategically organized and refined format for both industry and non-profit organizations. Regulatory Perspectives from the FDA & EMEA will provide global advice for successful commercialization; Scientists from Siena Biotech, NIH & Novartis will help understand common orphan disease mechanisms; and the National Organization for Rare Disorders (NORD) will describe effective mentoring strategies for new orphan disease companies to ensure success.
    For further details

    International Conference on Rare Diseases and Orphan Drugs (ICORD 2009)
    Date: 23-25 February 2009
    Venue: Rome, Italy

    The preliminary programme for the next ICORD meeting is now available.
    For further details

    Second International Rare Disease Day
    Date: 28 February 2009
    Venue: Everywhere!

    “Patient Care: A Public Affair!” is the focus of 2009 Second International Rare Disease Day. Check with the official website to locate activities in your region.
    For further details

    BPSU 2009 Conference
    Date: 3 March 2009
    Venue: London, England

    The British Paediatric Surveillance Unit (BPSU) has put together a programme that reviews the contribution the BPSU has made to the understanding and control of uncommon childhood conditions, it’s impact on public health policy and it’s development of partnerships.
    For further details

    Genomic Disorders Conference
    Date: 9-11 March 2009
    Venue: Cambridge, England

    Building on the success of two previous meetings held in 2007 & 2008, Genomic Disorders 2009 aims to present an exciting blend of genomic science and clinical science. The meeting will discuss the latest findings relating to the genomic basis of human variation, congenital disorders and acquired diseases including complex traits.
    For further details

    3rd International Congress on Rare Pulmonary Diseases and Orphan Drugs
    Date: 20-21 March 2009
    Venue: Milan, Italy

    This conference will consider new issues in rare pulmonary diseases and examine aspects of individual disorders.
    For further details

    Molecular Mechanisms of Neurodegeneration
    Date: 8-10 May 2009
    Venue: Milan, Italy

    Addressing the most important issues involved in protein toxicity in neurons, providing participants with updated information that could be useful to researchers in the field of neurodegenerative disorders.
    For further details

    7th World Congress on Melanoma
    Date: 12-16 May 2009
    Venue: Vienna, Austria

    A joint meeting with the 5th Congress of the European Association of Dermato-Oncology. Clinicians and researchers will focus on the state of the art in prevention, recognition, and treatment of cutaneous neoplasms covering melanoma and non melanoma skin cancer as well as lymphomas and rare skin tumours. Deadline for submission of abstracts: 31 January, 2009.
    For further details

    8th Balkan Meeting on Human Genetics
    Date: 14-17 May 2009
    Venue: Cavtat, Croatia

    "Rare diseases – public policy, research, diagnosis and management" is one of the topics featured in this conference. Deadline to submit an abstract is 20 January 2009.
    For further details

    Conference on Recent Standards in Diagnosis, Treatment and Medical Care for Some Rare Neuromuscular Diseases
    Date: 21-23 May 2009
    Venue: Kharkiv, Ukraine

    The agenda will include: Spinal muscular atrophy - modern and newest approaches to diagnostics and treatment; Duchenne muscular dystrophy - modern and newest approaches to diagnostics and treatment; other rare neuromuscular pathologies - latest approaches to diagnostics and treatment; management of respiratory system; orthopaedic aspects; organisation of medical service for rare neuromuscular disorders (diagnosis, registering, conducting of clinical trials and research in compliance with principles of GMP); and more.
    For further details

    The Fourth European Molecular Imaging Meeting
    Date: 27-30 May 2009
    Venue: Barcelona, Spain

    By bringing together top European scientists from various disciplines working in the field of molecular imaging, this high-level meeting will foster the coherence of a sustainable European Molecular Imaging Community with the common goal to translate fundamental research discoveries into medical application and health benefit for the European Society.
    For further details

    12th International Congress on Neuronal Ceroid Lipofuscinoses
    Date: 3-6 June 2009
    Venue: Hamburg, Germany

    The aim of this meeting is to facilitate and speed up exchange between expert scientists and physicians, but also to confront young researchers with the challenges of the largest group of degenerative brain diseases in young people. Deadline for submission of abstracts: 28 February, 2009.
    For further details

    Porphyrins and Porphyrias 2009
    Date: 14–18 June 2009
    Venue: Stockholm, Sweden

    The scientific program will cover the latest developments in the field of heme-related disorders. The meeting will include plenary sessions, oral presentations and poster presentations. Contributions will be made from basic scientists, molecular biologists, laboratory and clinical academicians, clinical researchers and physicians working in the field of heme metabolism and heme-related disorders.
    Deadline for abstract submission: 1 March 2009.
    For further details

    Fourth International Conference on Birth Defects and Disabilities in the Developing World
    Date: 4-7 October 2009
    Venue: New Delhi, India

    The theme of the Fourth International Conference is "Translating Research into Cost-effective Services for the Care and Prevention of Birth Defects, Preterm Birth and Consequent Disabilities". Deadline for submission of abstracts: 15 April, 2009.
    For further details

    TREAT-NMD/NIH International Conference
    Date: 17-19 Nov 2009
    Venue: Brussels, Belgium

    The aim of the meeting is to share progress in the area of translational medicine in inherited neuromuscular diseases and set the future collaborative agenda. This conference will build on achievements of the NIH and TREAT-NMD. It will be a highly interactive meeting with a strong focus on the key issues surrounding "trial readiness" in the neuromuscular field.
    For further details


    Press & Publications
    The rare disease encountered in general practice: a survey from the Netherlands
    A paper appearing in the review European Journal of General Practice explores the prevalence of rare diseases encountered in general practice in the Netherlands. Extracting data over a twenty-year period from the Continuous Morbidity Registration (CMR) Nijmegen, which gathers statistics from general practices in and around Nijmegen, the authors use the Orphanet database as a point of comparison. Of 71 codes of rare diseases retrieved, 51 could be subdivided into malignancies, specific infections, diseases of short duration, and chronic diseases. Twenty (36%) of these 56 diseases were also listed in the Orphanet database (mostly malignancies and chronic diseases). The authors hypothesise that a low number of rare diseases were found in the CMR because no specific code exists for many disorders: “Rare diseases for which no specific code exist are registered in a ‘rest category’ in the database and can only be retraced by manually searching the original files”. The authors suggest that study of the prevalence of rare diseases in general practice could be improved by changes in methods of registration: “Electronic patient files offer the opportunity to export more detailed information concerning diagnosis to the central database. Textual information could be exported and translated by investigators to, for example, ICD codes, which are much more detailed than e-List or ICPC codes”. Another interesting conclusion: while the literature emphasises rare chronic diseases, the general practitioner also confronts rare diseases of shorter duration.
    Consult the PubMed abstract

    Humbly receptive: the role of the paediatrician in the rare disease support group
    A brief but instructive article appearing in the review Acta Paediatrica considers the appropriate role for the paediatrician collaborating with a rare disease patient group. Such groups have proven empowering for patients and their families - who often face a scarcity of recognition, information and resources. The emergence of the “patient-expert” in the domain of rare diseases does not lead to autonomy from the medical establishment but rather a more informed partnership with medical professionals. The American Academy of Pediatrics encourages paediatricians to participate in community-based support groups. Such professionals can furnish patients with health and safety technical advice while gaining for themselves greater insight into how to best support patients and their families. Paediatricians are cautioned to avoid adopting the role of personal physician. Instead the author says that these professionals must be “humbly receptive” – considering an alliance with a patient group as beneficial (and even necessary) to the quality of their work. Participating in conferences, disseminating information, reinforcing networks that bring together patients and professionals, lobbying for patients’ rights, and establishing or contributing to scientific boards, can all figure amongst the tasks of the paediatrician working with a rare disease support group. Such responsibilities are “likely to contribute to the paediatrician’s own continuing education, particularly in communication skills and perception of issues…”.

    The paediatrician’s role in support groups for rare diseases
    Acta Pædiatrica 2008 97, pp. 1510–1511


    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, Olaf Bodamer, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
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