11 March 2009 print
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Orphanet completes first chapter of an immense project to render rare diseases more visible in the WHO classification system

The World Health Organization (WHO) oversees the International Classification of Diseases (ICD), the global standard for reporting and categorising diseases. This system serves to "capture snapshot views of population health using such parameters as death, disease, functionality, disability, health and health interventions, which inform management and decision making process in the health system". Tracking the prevalence, morbidity and mortality of rare diseases is especially crucial in order to make the most of limited resources, organise research and trials, and develop the most efficient policy toward the 7,000-plus rare disorders identified to date. Currently, only 250 rare diseases are present in the ICD with their own specific code.

A WHO Topic Advisory Group for rare diseases was established in April 2007 to render rare diseases traceable in mortality and morbidity information systems. The production of the basic information to establish a first draft of the classification of rare diseases was assigned to Orphanet and may serve as a template for the whole revision process as rare diseases involve all areas of medicine.

Orphanet, with its comprehensive peer-reviewed database of information on rare diseases containing over 5,800 inventoried diseases, updated regularly according to the evolution of knowledge, is the ideal partner for the immense task of revising the ICD to include rare disorders. Each Orphanet entry is already indexed with MeSH terms, Orphanet thesaurus of clinical signs and symptoms, ICD-10 codes, and linked to the OMIM database, to an in-house genes database and to PubMed as well as to other websites of interest. Each Orphanet entry has an identity card with epidemiological data (prevalence rank, mode of inheritance, age of onset) and a set of synonyms. Orphanet produces a peer-reviewed encylopaedia of more than 2,600 entries that are added to and updated continuously.

In order to prepare the ICD revision process, Orphanet collected a series of rare diseases classifications mainly based on scientific grounds (aetiology and mechanism). To complement these classifications, Orphanet has developed a strictly clinical in-house classification to meet the needs of the clinicians, funded by the French Health Authority. All the classifications can be viewed on the Orphanet website. These serve as a basis to build the ICD-11 proposals, with support from DG Sanco. Learn more about the Orphanet classification

Orphanet has completed its first ICD chapter revision. Chapter III: Diseases of the blood and blood-forming organs, has been updated to render rare diseases traceable. For each disease entered or revised, Orphanet provides thorough, documented rationale. Experts from each continent are now being identified to review the revisions to ICD Chapter III. After expert review, the revision proposals will be open to public consultation.

In the meantime, Orphanet is busying itself to revise the next chapter, Endocrine, nutritional and metabolic diseases. Orphanet is planning to revise a new chapter every few weeks.
Learn more about the WHO ICD revision process

Spotlight on...
A growing trend? The UK’s NHS funds a second rare disease
patient group-health professional partnership


Following the success of a collaborative effort between medical professionals and rare disease patient organisation the Alström Syndrome UK Support Group, who are working in tandem to furnish medical services and treatments for patients with Alström syndrome (see the 30 April 2008 issue of OrphaNews Europe), the National Commissioning Group for Highly Specialised Services of the United Kingdom’s National Health Service is now funding a second partnership, this time for rare disorder ataxia-telangiectasia. Ataxia-Telangiectasia (A-T) associates severe combined immunodeficiency (affecting mainly the humoral immune response) with progressive cerebellar ataxia. A rare, complex, genetic disorder that results in progressively severe disability and premature death, there is currently neither cure nor treatment. The A-T Society, a patient support group founded in 1989, is one of the principles in the new NHS-funded collaboration. A-T Society treasurer Vincent Poupard describes for OrphaNews Europe the logistics of the collaboration:

In 1993, the A-T Society, a patient support group founded in 1989, established the National A-T Clinic at Nottingham City Hospital in England. The motivation to take this measure came from a sense of frustration experienced by parents at the lack of expert knowledge of the disease at their local level. These parents of children with A-T instinctively understood that a central clinic, staffed by a multi-disciplinary medical team with access to potentially all A-T patients in the UK, could evolve into centre of expertise for the management of the disease and that the fruits of this understanding could serve as a resource to local healthcare teams throughout the UK. There are some 200 A-T patients in the UK.

Now, from 1 April, 2009, the National A-T Clinic will be funded on behalf of the UK’s National Health Service via the National Commissioning Group for Highly Specialised Services. Under this new arrangement, each clinic will be extended to two days of individual consultations, with greater opportunity for additional appropriate testing. The frequency of clinics will progressively increase so that by 2011 there will be six per year - on average, one clinic every other month. The number of patients seen is expected to increase to eight or nine per clinic. Ideally, each patient will be recalled at intervals of no more than 24 months. (Currently clinics are held three times a year, during which six patients attend each time for one day of tests and consultations).

Although patients may be referred directly to the clinic, most visits will be scheduled by the A-T Society’s Family Support Worker in liaison with the City Hospital. Where necessary, the Society arranges accommodation and transportation for families and even offers financial support to defray travelling expenses. Representatives from the Society attend each clinic, both to chaperone the families and to act as liaison between them, the medical professionals, and the City Hospital bureaucracy.

From its inception, the clinic has consisted of a partnership between the City Hospital and the A-T Society. The Society not only identified and nominated patients but also funded certain expenses. In the early days, families were offered consultations with a neurologist and a geneticist, but over the years the range of clinical disciplines available has been significantly expanded. Today a patient can expect to see up to nine different clinicians and therapists.

Adopting a holistic approach, some sessions are organised with the experts working in groups; for example, in the therapy session a family will see together the physiotherapist, the occupational therapist, the speech and language therapist and the dietician. Next, the same family will see the neurologist, and at the third session will meet with the geneticist and immunologist. In addition, blood tests, basic observations (height, weight, etc.) and lung function tests are also performed. Feedback is communicated to the patient’s local care team.

The A-T Society considers itself very fortunate to have a team supporting the clinic that is focused and enthusiastic about the A-T cause. The very real health care benefits that have been made possible for young people with A-T are the result of an effective and productive partnership between the patient organisation and the health care professionals.

Although a specifically English and Scottish response to a world-wide medical need, the novel structure of the clinic with its partnership of patient group, hospital, and national health service, may serve as a model that other countries in Europe and throughout the world could adapt to fit their own particular circumstances.
Contact the A-T Society


EU Policy News
European Commission health work plan for 2009 continues supporting rare disease projects and networks
The European Commission on 23 February adopted a Work Plan for 2009 implementing the second programme of Community action in the field of health (2008-2013). Amongst the rare disease initiatives earmarked for funding are two calls for tenders that contribute to the implementation of the Commission Communication on Rare Diseases: Europe’s challenges: 1) evaluation of population newborn screening practices in Member States; and 2) repertorying rare disease information, diagnosis and treatment using existing European initiatives (in particular Orphanet). To support rare disease pilot reference networks and networks of information, there is a call for proposals for new projects as well as a call for operating grants that enable existing networks to continue. Consult the details of the EC Work Plan
European Commission moves forward process of increasing transparency in clinical trials for children
New measures were moved forward in February to expand the transparency of information on clinical trials for medicinal products involving paediatric populations. The Guidance on the information concerning paediatric clinical trials to be entered into the EU Database on Clinical Trials (EudraCT) and on the information to be made public by the European Medicines Agency (EMEA), in accordance with Article 41 of Regulation (EC) No 1901/2006, published in the 04 February 2009 Official Journal of the European Union, is designed to “increase the availability of information on the use of medicinal products in the paediatric population and to avoid unnecessary repetition of studies”. The guidance delineates the information to be registered with EudraCT, the clinical trials database of the European Union and concerns both trial protocol and trial results. The data to be furnished are destined for both the general public and for professionals in the fields of medicine, research, and the pharmaceutical industry. The guidelines also set out the timeframe for providing information and the means through which information is to be made available. The European Medicines Agency has the task of revising EudraCT to render the specified information public. A draft of the guidance underwent a period of public consultation in 2008. With an estimated 80% of all rare disorders affecting children, this measure to increase transparency is expected to augment the safety and efficacy of treatment development for this population.
Consult the European Commission guidance on paediatric trial transparency
Consult the fields to be made public in the EudraCT clinical trials database


National & International Policy Developments
Portuguese rare disease plan meets the approval of country’s health minister
On 12 November, 2008, the Portuguese Minister of Health approved a national plan for rare diseases for Portugal. The plan, still being translated into English, adheres closely to the structure outlined during the European Conference on Rare Diseases that took place in Lisbon in 2007, according to a source. The Programa Nacional de Doenças Raras, which has already undergone a period of public consultation, delineates two general and seven specific objectives and will be implemented within an initial timeframe to run from 2008-2010 followed by a consolidation period stretching from 2010-2015. The specifics of the plan include some 30 intervention strategies, nine training strategies, and eight strategies for data collection and information analysis. The plan also details 15 actions for evaluation. The Minister will choose a coordinator and a national commission to oversee and put into action the various elements of the plan. It is estimated that Portugal has between 600 000 and 800 000 cases of rare pathology, the majority of which have a prevalence below 1 in 100 000. For more details of the preliminary version of Portugal’s national plan for rare diseases, consult the third chapter of the conference report of the 2007 European Conference on Rare Diseases (section 3.3).
Non-invasive prenatal testing: ten commandments for responsible use of a new technology
It has been over a decade since the discovery that cell-free foetal DNA is present in maternal blood during pregnancy. This DNA is detectable from seven weeks gestation. New technology to identify foetal DNA can detect specific genetic traits. While considered safer and earlier than its invasive counterparts, this new approach merits serious and studied consideration before being admitted into clinical practice. A new report, issued in January by the PHG Foundation, an independent not-for-profit public health organisation “focusing on the translation of science and biomedical innovation to improve health; especially genome-based science and technologies” brings together key experts - clinicians (including general practitioners, obstetricians, midwives and geneticists), scientists, government representatives, public health experts, ethicists, and patient organisations – to formulate recommendations designed to guide responsible and effective use of non-invasive cell-free foetal Nucleic Acid (cffNA) technology. Created for the UK National Health Service, the report is applicable to any country trying to determine the place non-invasive foetal testing may have in its repertoire of prenatal diagnostic services. Ethical, legal and social issues associated with the technology are also addressed. Amongst the key findings, the report issues ten key recommendations for the responsible, best practice of this emerging technology:

  • 1) Non-invasive prenatal diagnosis (NIPD) using cell-free fetal DNA (and RNA) is likely to become increasingly available within the next 3-5 years, and the NHS should take steps now to ensure that it is able to respond in a timely and appropriate manner as the technology develops
  • 2) Public engagement is urgently needed and should be pro-actively pursued with a clear, accurate and consistent message that recognises the limitations of cffNA testing
  • 3) Professional education is urgently needed, particularly for key health care workers, and should be started immediately by relevant professional bodies
  • 4) Formal evaluation of the use of cffNA testing for each application within a specified care pathway should be undertaken prior to implementation within the NHS
  • 5) Formal audit and monitoring processes should be established for all non-invasive prenatal tests based on cffNA technology
  • 6) National best practice guidelines should be developed by key clinical services to ensure that cffNA testing is only used within agreed clinical pathways
  • 7) Standard protocols should be developed by expert laboratory services that include the whole care pathway, supplemented by quality assurance frameworks to ensure accuracy, reliability and comparability of results
  • 8) Private NIPD services are already available on a direct-to-consumer basis, which will impact on NHS services; although the extent to which regulation can and should be applied to these services is debatable, development of a voluntary code of conduct should be supported to help ensure quality
  • 9) Oversight from appropriate statutory authorities is needed to ensure responsible, effective and timely implementation of cffNA technology for NIPD within the NHS
  • 10) Additional research is needed to investigate some of the broader implications of cffNA testing for NIPD

  • NIPD could be used for aneuploidies, sex-linked disorders, certain endocrine diseases, and some rare monogenic conditions (particularly those in which the paternal disease-causing allele differs from the maternal one). The report Cell-free nucleic acids for non-invasive prenatal diagnosis is freely available on the PHG Foundation website.

    Other European news
    Spanish congress on orphan drugs and rare diseases makes a declaration

    On 19-21February the IV International Congress on Orphan Drugs and Rare Diseases took place in Seville, Spain with more than 300 participants in attendance - patients associations, physicians, researchers, policy makers and pharmacists. This congress, organized by the Royal College of Pharmacists from Seville and the Spanish Federation of Associations on Rare Diseases (FEDER), a national alliance member of EURORDIS, is the fourth in a series that commenced in 2002, following the adoption in 2000 of the European regulation on Orphan Drugs. This year, congress participants approved the “Seville Declaration” a document consisting of 17 different recommendations of actions for both regional and national level government to undertake in order to improve the quality of life of rare disease families and patients.

    Other International News
    Second International Rare Disease Day a rousing success

    The early consensus of the Second Annual International Rare Disease Day that took place at the end of February, is that the event was a major success - particularly when it came to promoting the issues behind this year’s theme: Patient Care: a Public Affair. Patient groups, policy makers, health professionals, industry, and researchers from far and wide got in on the action. The launch of a new book The Voice of 12,000 Patients produced by the European Organisation for Rare Diseases (EURORDIS) and co-funded by the European Commission, took place in Brussels, hosted by Commissioner for Health Androulla Vassiliou. OrphaNews Europe will provide a detailed account in the next issue.


    Ethical, Legal & Social Issues
    Choosing not to choose: the ambivalence of parents of affected children toward both future pregnancies and screening technology
    An article published in the January 2009 issue of the review Sociology of Health and Illness presents a qualitative study of the attitudes of parents who have given birth to children with rare genetic disorders both toward future pregnancies and invasive and non-invasive prenatal screening technologies. The choices of parents with affected children reflect “a deep-seated ambivalence”. Amongst an array of possible choices for these parents is the decision not to choose. The study, situated in a rural region of the mid-southern USA and including parents of children with Fragile X syndrome, Lesch-Nyhan syndrome, Marfan syndrome, neurofibromatosis, Prader-Willi syndrome, Rett syndrome, and Turner syndrome, amongst other disorders, reports that over two-thirds of the parents in the study preferred to avoid future pregnancies rather than undergoing testing to identify possible conditions: “Avoiding future reproduction resolved the difficulty of actively choosing among troubling outcomes – not accepting prenatal screening or testing and risking a future affected pregnancy; accepting prenatal screening or testing with the possible outcome being termination of the pregnancy; or, alternatively, ‘choosing’ to bring an affected child into the world”. As the article reveals, the choice to avoid reproduction is “shaped by a heightened sense of the risks inherent in reproduction and of the limits of medicine’s ability to predict and control them. For many parents, first-hand experience with a child’s impairment connected their personal decisions with larger societal discourses about disability”. This sensitively rendered study includes the testimonies of mothers of children diagnosed with rare disorders. Of those parents who did go on to have further children, a majority made the decision not to undergo prenatal screening technology.
    The study is freely available online.

    Paediatric cancer: clinical trials in Europe are still a long way from harmonisation
    Clinical trials for children with cancer have been particularly hard hit by the introduction of the EU Clinical Trials Directive in 2004. Largely investigator-led and lacking in commercial sponsorship, they have struggled to find the resources necessary to comply with the complex bureaucracy. These rare diseases require multinational participation to permit appropriately powered clinical trials to be undertaken. Differences in interpretation of the Directive by national regulatory authorities have had a disproportionate effect on trials in children, highlighted by differences in what is deemed an ‘investigational medicinal product’ when paediatric use of an old drug is outside its licensed indication. Insurance costs have increased a 100-fold with no increase in actual risk between consecutive trials from the same study group. Issues raised at the recent conference held to reappraise the operation of the Directive are summarised to emphasise the particular issues for trials in children with cancer.
    Read the PubMed abstract

    Eur J Cancer ; 2106-2111 ; October 2008

    Orphanet News
    Orphanet celebrates ten years of HONourable behaviour

    Orphanet is celebrating ten years of HON certification. HONcode - the Health on the Net Foundation seal of approval – is a visible sign that an internet health information website is disseminating reliable, accurate information conforming to ethical standards. HON is a “non-profit, non-governmental organization, accredited to the Economic and Social Council of the United Nations”. Orphanet received HON certification in December 1998. Of the estimated four billion health-related pages available on the internet, some 5000 sites from 72 different countries have adopted the HONcode. To qualify for HONcode certification, a site must furnish eight key pieces of information concerning “from which authority the information is coming from; what is the purpose of the site; the confidentiality policy; the origin of the sources used; the justification about benefits and performance of a specific treatment; the transparency of the authorship; the actualization of health data; the transparency of sponsorship as well as honesty in advertising and editorial policies”.
    Visit the HON website

    New Texts
    New Orphanet Journal of Rare Diseases publications
    Jacobsen syndrome

    New Genes
    Primary ciliary dyskinesia: a newly-discovered gene is involved in the cytoplasmic pre-assembly of axonemal dyneins
    Motility defects in cilia and flagella often result in primary ciliary dyskinesia, a heterogeneous group of disorders characterised by chronic bronchorrhea with bronchiectasis and chronic sinusitis. The mechanisms underlying cilia formation and function, and in particular the cytoplasmic assembly of dyneins that power ciliary motility, are poorly understood. The authors report a new gene, KTU, involved in this cytoplasmic process. This gene was first identified in a medaka mutant, and found to be mutated in primary ciliary dyskinesia patients from two affected families.
    Read the PubMed abstract

    To read more about "Primary ciliary dyskinesia"

    Nature ; 611-616 ; 4 December 2008
    Autosomal nonsyndromic intellectual deficit: mutations in SYNGAP1 found
    Although autosomal forms of nonsyndromic intellectual deficit account for the majority of cases of intellectual deficit, the genes that are involved remain largely unknown. The authors identified mutations in autosomal gene SYNGAP1, which encodes a Ras GTPase-activating protein that is critical for cognition and synapse function, in three of 94 patients with nonsyndromic intellectual deficit.
    Read the PubMed abstract

    To read more about "Autosomal recessive nonsyndromic intellectual deficit"

    N Engl J Med ; 599-605 ; 5 February 2009
    RIDDLE syndrome protein mediates an ubiquitin-dependent signalling cascade at sites of DNA damage
    The biological response to DNA double-strand breaks acts to preserve genome integrity. Individuals bearing inactivating mutations in components of this response exhibit clinical symptoms that include cellular radiosensitivity, immunodeficiency, and cancer predisposition. The archetype for such disorders is Ataxia-Telangiectasia, caused by biallelic mutation in ATM, a central component of the DNA damage response. Here, the authors report that the ubiquitin ligase RNF168 is mutated in the RIDDLE syndrome, a recently discovered immunodeficiency and radiosensitivity disorder, and demonstrate that RNF168 is recruited to sites of DNA damage by binding to ubiquitylated histone H2A.
    Read the PubMed abstract

    Cell ; 420-434 ; 6 February 2009
    Neuromuscular diseases: updated gene table available online
    An updated list of monogenic muscle diseases in which the causative nuclear gene is known, or at least localised on a chromosome, is available via the Gene Table of Neuromuscular Disorders. Freely available online, the 2009 full version contains 481 clinical entries and 243 distinct identified genes. The table was created in 1991 for the first issue of the review Neuromuscular Disorders.

    Research in Action
    Fundamental Research
    Ethylmalonic encephalopathy: loss of a mitochondrial dioxygenase causes fatal sulfide toxicity
    Ethylmalonic encephalopathy is an autosomal recessive, invariably fatal disorder characterised by early-onset encephalopathy, microangiopathy, chronic diarrhea, defective cytochrome c oxidase (COX) in muscle and brain, high concentrations of C4 and C5 acylcarnitines in blood and high excretion of ethylmalonic acid in urine. ETHE1, a gene encoding a beta-lactamase-like, iron-coordinating metalloprotein, is mutated in ethylmalonic encephalopathy. In bacteria, ETHE1-like sequences are in the same operon of, or fused with, orthologs of TST, the gene encoding rhodanese, a sulfurtransferase. In eukaryotes, both ETHE1 and rhodanese are located within the mitochondrial matrix. The authors created a Ethe1(-/-) mouse that showed the cardinal features of ethylmalonic encephalopathy. They found that thiosulfate was excreted in massive amounts in urine of both Ethe1(-/-) mice and humans with ethylmalonic encephalopathy. High thiosulfate and sulfide concentrations were present in Ethe1(-/-) mouse tissues. Sulfide is a powerful inhibitor of COX and short-chain fatty acid oxidation, with vasoactive and vasotoxic effects that explain the microangiopathy in ethylmalonic encephalopathy patients. Sulfide is detoxified by a mitochondrial pathway that includes a sulfur dioxygenase. Sulfur dioxygenase activity was absent in Ethe1(-/-) mice, whereas it was markedly increased by ETHE1 overexpression in HeLa cells and Escherichia coli. ETHE1 is a mitochondrial sulfur dioxygenase involved in catabolism of sulfide that accumulates to toxic levels in ethylmalonic encephalopathy.
    Read the PubMed abstract

    To read more about "Encephalopathy, ethylmalonic"

    Nat Med ; 200-205 ; February 2009
    Congenital insensitivity to pain: Neural correlates of empathy in patients
    Patients with the rare syndrome of congenital insensitivity to pain cannot rely on "mirror matching" (i.e., resonance) mechanisms to understand the pain of others. Nevertheless, they showed normal fMRI responses to observed pain in anterior mid-cingulate cortex and anterior insula, two key regions of the so-called "shared circuits" for self and other pain. In these patients (but not in healthy controls), empathy trait predicted ventromedial prefrontal responses to somatosensory representations of others’ pain and posterior cingulate responses to emotional representations of others’ pain. These findings underline the major role of midline structures in emotional perspective taking and understanding someone else’s feeling despite the lack of any previous personal experience of it--an empathic challenge frequently raised during human social interactions.
    Read the PubMed abstract

    To read more about "Congenital insensitivity to pain"

    Neuron ; 203-212 ; 29 January 2009
    Clinical Research
    Stevens-Johnson syndrome and toxic epidermal necrolysis: a pooled analysis of medications as risk factors in children
    The authors conducted a pooled analysis by using data from 2 multicenter international case-control studies: the severe cutaneous adverse reaction (SCAR) study and the multinational severe cutaneous adverse reaction (EuroSCAR) study conducted in France, Germany, Italy, Portugal, the Netherlands, Austria, and Israel. They selected case subjects aged <15 years, hospitalized for Stevens-Johnson syndrome, Stevens-Johnson syndrome/toxic epidermal necrolysis-overlap, or toxic epidermal necrolysis, and age-, gender-, and country-matched hospital controls. They confirmed 4 previously highly suspected drug risk factors for Stevens-Johnson syndrome/toxic epidermal necrolysis in children: antiinfective sulfonamides, phenobarbital, carbamazepine, and lamotrigine. Among more unexpected risk factors, they suspect that acetaminophen (paracetamol) use increases the risk of Stevens-Johnson syndrome or toxic epidermal necrolysis.
    Read the PubMed abstract

    To read more about "Stevens-Johnson syndrome"
    To read more about "Toxic epidermal necrolysis"

    Pediatrics ; 297-304 ; February 2009
    Congenital diaphragmatic hernia: timing of delivery and survival rates for infants with prenatal diagnoses
    A retrospective cohort study of term infants with prenatal diagnoses of congenital diaphragmatic hernia was performed with the Congenital Diaphragmatic Hernia Study Group Registry of patients with congenital diaphragmatic hernias who were treated between January 1995 and December 2006. Among 628 term infants at 37 to 41 weeks of gestation who had prenatal diagnoses of congenital diaphragmatic hernia and were free of major associated anomalies, early term birth (37 vs 39-41 weeks) and greater birth weight were associated independently with survival, whereas black race was related inversely to survival. Infants born at early term with birth weights at or above the group mean (3.1 kg) had the greatest survival rate (80%). Among infants born through elective cesarean delivery, infants born at 37 to 38 weeks of gestation, compared with 39 to 41 weeks, had less use of extracorporeal membrane oxygenation (22.0% vs 35.5%) and a trend toward a greater survival rate (75.0% vs 65.8%).
    Read the PubMed abstract

    To read more about "Diaphragmatic hernia, congenital"

    Pediatrics ; 494-502 ; February 2009
    Acute lymphoblastic leukaemia: a genome-wide classification study of a childhood subtype characterised by poor outcome
    Genetic subtypes of acute lymphoblastic leukaemia (ALL) are used to determine risk and treatment in children. 25% of precursor B-ALL cases are genetically unclassified and have intermediate prognosis. The authors used a genome-wide study to improve prognostic classification of ALL in children by constructing a classifier based on gene expression. Hierarchical cluster analysis with classifying gene-probe sets revealed a new ALL subtype. Hierarchical clustering showed that many of these genetically unclassified cases clustered with BCR-ABL1-positive cases. 36 of the patients with BCR-ABL1-like disease had deletions in genes involved in B-cell development, including IKZF1, TCF3, EBF1, PAX5, and VPREB1. New treatment strategies are needed to improve outcome for this newly identified high-risk subtype of ALL.
    Read the PubMed abstract

    To read more about "Leukemia, lymphoblastic, acute"

    Lancet Oncol ; 125-134 ; February 2009
    Acute lymphoblastic leukaemia: prognosis of disease with IKZF1 gene deletion
    Despite best current therapy, up to 20% of paediatric patients with acute lymphoblastic leukemia (ALL) have a relapse. The authors studied a cohort of 221 children with high-risk B-cell-progenitor ALL with the use of single-nucleotide-polymorphism microarrays, transcriptional profiling, and resequencing of samples obtained at diagnosis. A copy-number abnormality was identified as a predictor of poor outcome, and it was then tested in an independent validation cohort of 258 patients with B-cell-progenitor ALL. More than 50 recurring copy-number abnormalities were identified, most commonly involving genes that encode regulators of B-cell development; PAX5 was involved in 31.7% and IKZF1 in 28.6% of patients. Poor outcome was strongly associated with alteration of IKZF1, a gene that encodes the lymphoid transcription factor IKAROS.
    Read the PubMed abstract

    To read more about "Leukemia, lymphoblastic, acute"

    N Engl J Med ; 470-480 ; 29 January 2009
    Congenital ichthyosis: novel transglutaminase-1 mutations and genotype-phenotype investigations
    Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary disorder of cornification. Mutations in the transglutaminase-1 (TGM1) gene, which encodes for the epidermal enzyme transglutaminase-1 (TGase-1), are one of the causes of ARCI. The authors characterised the TGM1 mutation spectrum and investigated genotype-phenotype correlations in 104 patients. This study expands the TGM1 mutation spectrum and confirms that despite genetic and phenotypic heterogeneity in ARCI, TGM1 is the main causative gene for this disorder.
    Read the PubMed abstract

    To read more about "Ichthyosis, lamellar"

    J Med Genet ; 103-111 ; February 2009
    Silver-Russell syndrome: the degree of H19 hypomethylation linked to phenotype severity and genital and skeletal anomalies
    Silver-Russell syndrome (SRS) is characterised by growth retardation with antenatal onset, characteristic facies and limb asymmetry. The authors found a dose-response relationship between the degree of H19 hypomethylation and phenotype severity in SRS. They report for the first time the association of specific anomalies of the spine, elbows, hands and feet, and genital defects in SRS with severe H19 hypomethylation. Classical SRS features were found in H19 hypomethylation and milder symptoms in maternal uniparental disomy of chromosome 7, thus distinguishing two separate clinical and etiological subgroups.
    Read the PubMed abstract

    To read more about "Silver-Russell syndrome"

    J Clin Endocrinol Metab ; 579-587 ; February 2009
    Antiphospholipid syndrome: clinical and diagnostic considerations
    The antiphospholipid syndrome (APS) is an acquired thrombophilia, characterised by the occurrence of venous and arterial events. This article examines the laboratory and key clinical aspects of APS. Particular focus is given to anti-beta 2-glycoprotein I (beta(2)GPI) antibodies in view of their recent inclusion in the APS classification criteria. The clinical utility of using the beta(2)GPI enzyme-linked immunosorbent assay, in conjunction with the established lupus anticoagulant assays and cardiolipin enzyme-linked immunosorbent assay, for diagnosing and risk stratifying patients suspected of having APS is discussed. The implications of recent epidemiologic findings for possibly understanding the underlying pathophysiologic mechanisms of obstetric APS are highlighted. Insights into which patients with obstetric APS may be at most risk of thrombotic complications are presented.
    Read the PubMed abstract

    To read more about "Antiphospholipid syndrome"

    Blood ; 985-994 ; 29 January 2009
    Therapeutic Approaches
    Epidermolysis bullosa: improvement by transfer of wild-type bone marrow cells
    The recessive dystrophic form of epidermolysis bullosa (RDEB) is a disorder of incurable skin fragility and blistering caused by mutations in the type VII collagen gene (Col7a1). The absence of type VII collagen production leads to the loss of adhesion at the basement membrane zone due to the absence of anchoring fibrils, which are composed of type VII collagen. The authors report that wild-type, congenic bone marrow cells homed to damaged skin, produced type VII collagen protein and anchoring fibrils, ameliorated skin fragility, and reduced lethality in the murine model of RDEB generated by targeted Col7a1 disruption. These data provide the first evidence that a population of marrow cells can correct the basement membrane zone defect found in mice with RDEB and offer a potentially valuable approach for treatment of human RDEB and other extracellular matrix disorders.
    Read the PubMed abstract

    To read more about "Epidermolysis bullosa, dystrophic"

    Blood ; 1167-1174 ; 29 January 2009
    Fragile X syndrome: minocycline promotes dendritic spine maturation and improves behaviour in mouse model
    Fragile X syndrome (FXS) is the most common single gene inherited form of intellectual delay, with behaviours at the extreme of the autistic spectrum. Subjects with FXS and fragile X intellectual delay gene knock out (Fmr1 KO) mice, an animal model for FXS, have been shown to exhibit defects in dendritic spine maturation that may underlie cognitive and behavioural abnormalities in FXS. Minocycline is a tetracycline analogue that has been used in clinical trials for stroke, multiple sclerosis and several neurodegenerative conditions. The authors evaluated the effects of minocycline on dendritic spine development in the hippocampus of young Fmr1 KO mice, and in primary cultures of hippocampal neurons isolated from those mice. Their studies demonstrate that minocycline promotes dendritic spine maturation both in cultures and in vivo. The beneficial effects of minocycline on dendritic spine morphology are also accompanied by changes in the behavioural performance of 3-week-old Fmr1 KO mice.
    Read the PubMed abstract

    To read more about "Fragile X syndrome"

    J Med Genet ; 94-102 ; February 2009
    Huntington disease: exendin-4 improves glycemic control, brain and pancreatic pathologies, and survival in mouse model
    The aim of this study was to find an effective treatment for the genetic form of diabetes that is present in some Huntington disease patients and in Huntington disease mouse models. Huntington disease mice were treated with an FDA-approved antidiabetic glucagon-like peptide 1 receptor agonist, exendin-4 (Ex-4), to test whether euglycemia could be achieved, whether pancreatic dysfunction could be alleviated, and whether the mice showed any neurological benefit. Ex-4 treatment ameliorated abnormalities in peripheral glucose regulation and suppressed cellular pathology in both brain and pancreas in the mouse model. The treatment also improved motor function and extended the survival time of the Huntington disease mice.
    Read the PubMed abstract

    To read more about "Huntington disease"

    Diabetes ; 318-328 ; February 2009
    Diagnostic Approaches
    Hemochromatosis: serum hyaluronic acid with serum ferritin predicts cirrhosis and reduces need for liver biopsy
    Diagnosing the presence of cirrhosis is crucial for the management of patients with hereditary hemochromatosis (HH). HH patients with serum ferritin >1,000 microg/L are at risk of cirrhosis; however, the majority of these patients do not have cirrhosis. Noninvasive markers of hepatic fibrosis may assist in determining which patients with a serum ferritin >1,000 microg/L have cirrhosis and require liver biopsy. This study evaluated the utility of current diagnostic algorithms for detecting cirrhosis, including serum ferritin concentration, platelet counts, and aspartate aminotransferase (AST) levels, in combination with serum markers of fibrosis, hyaluronic acid and collagen type IV (CLIV), in predicting cirrhosis in HH patients. They found that the measurement of hyaluronic acid in patients with serum ferritin >1,000 microg/L is a noninvasive, accurate, and cost-effective method for the diagnosis of cirrhosis.
    Read the PubMed abstract

    To read more about "Hemochromatosis"

    Hepatology ; 418-425 ; February 2009
    Newborn screening in Australia: an economic evaluation of tandem mass spectrometry
    Cost-effectiveness analysis from the health service perspective was undertaken for tandem mass spectrometry screening for conditions caused by rare errors of metabolism on the basis of registry data for affected individuals. The intervention group was contrasted with both a contemporaneous group in nonscreening states and a historical cohort. The registry covers all individuals identified in Australia between 1994 and 2002. Main outcome measures were the total net cost of screening, the cost of treatment, life-years saved, and deaths averted. The total net cost of testing was estimated to be A$218 000 (110766 euros) per 100 000 infants. Medical costs incurred by the intervention group exceeded those for the control group by A$131 000 per 100 000 infants. The number of life-years saved per 100 000 infants screened was 32.378 life-years per 100 000 infants through an expected mortality rate reduction of 0.738 deaths per 100 000 infants. The cost per death averted was estimated to be A$472 913 and the cost per life-year saved was estimated to be A$10 779, which compare favourably with existing cost-effectiveness standards. This conclusion is particularly robust because conservative assumptions were made throughout, because of data limitations. Sensitivity analyses suggested that this result was relatively robust to adjustment of model parameters. Tandem mass spectrometry screening for conditions caused by rare errors of metabolism is likely to be a cost-effective intervention in Australia.
    Read the PubMed abstract

    Pediatrics ; 451-457 ; February 2009

    Patient Management and Therapy
    Adenosine deaminase deficiency: gene therapy for immunodeficiency
    The authors investigated the long-term outcome of gene therapy for severe combined immunodeficiency (SCID) due to the lack of adenosine deaminase (ADA), a fatal disorder of purine metabolism and immunodeficiency. They infused autologous CD34+ bone marrow cells transduced with a retroviral vector containing the ADA gene into 10 children with SCID due to ADA deficiency who lacked an HLA-identical sibling donor, after nonmyeloablative conditioning with busulfan. Enzyme-replacement therapy was not given after infusion of the cells. All patients are alive after a median follow-up of 4.0 years (range, 1.8 to 8.0). Transduced hematopoietic stem cells have stably engrafted and differentiated into myeloid cells containing ADA and lymphoid cells. This study finds gene therapy, combined with reduced-intensity conditioning, to be a safe and effective treatment for SCID in patients with ADA deficiency.
    Read the PubMed abstract

    To read more about "Severe combined immunodeficiency due to adenosine deaminase deficiency"

    N Engl J Med ; 447-458 ; 29 January 2009
    Acromegaly: oral glucose tolerance testing not useful for assessment of treatment outcomes
    Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterised by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. GH suppression after oral glucose load [oral glucose tolerance test (OGTT)] and normal age- and gender-matched IGF-I levels reflect biochemical control of acromegaly. The OGTT is the gold standard for determining control of GH secretion at diagnosis and after surgical treatment, but the usefulness of performing an OGTT in patients treated with medical therapy has not been determined. The authors assessed relationships between basal GH levels (basal GH), GH responses to OGTT [GH nadir (GHn)], and IGF-I levels. 166 patients with acromegaly were included in the study. Four categories of testing were performed: diagnosis, postoperative assessment without medication, testing during somatostatin analog (SA) therapy, and testing during dopamine agonist (DA) therapy. Both basal and GHn levels are highly discordant with IGF-I levels during medical therapy with SAs. The OGTT is not useful in assessing biochemical control in these subjects.
    Read the PubMed abstract

    To read more about "Acromegaly"

    J Clin Endocrinol Metab ; 523-527 ; February 2009
    Fabry disease: early enzyme replacement therapy linked to better outcome for cardiomyopathy
    Enzyme replacement therapy with recombinant alpha-galactosidase A reduces left ventricular hypertrophy and improves regional myocardial function in patients with Fabry disease during short-term treatment. This study shows that treatment of Fabry cardiomyopathy with recombinant alpha-galactosidase A should best be started before myocardial fibrosis has developed to achieve long-term improvement in myocardial morphology and function and exercise capacity.
    Read the PubMed abstract

    To read more about "Fabry disease"

    Circulation ; 524-529 ; 3 February 2009
    Follicular lymphoma: stem cell transplantation has less relapse but more secondary tumours
    Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. This multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide. The 9-year overall survival (OS) was similar in the HDT and conventional chemotherapy groups (76% and 80%, respectively). The 9-year progression-free survival (PFS) was higher in the ASCT than the chemotherapy group (64% vs 39%). Secondary malignancies were more frequent in the HDT than in the chemotherapy group (6 secondary myelodysplastic syndrome/acute myeloid leukemia and 6 second solid tumor cancers vs 1 acute myeloid leukemia). A PFS plateau was observed in the HDT group after 7 years. The occurrence of a PFS plateau suggests that a subgroup of patients might have their FL cured by ASCT.
    Read the PubMed abstract

    To read more about "Follicular lymphoma"

    Blood ; 995-1001 ; 29 January 2009

    News from the Patients' Associations
    Raising money for the rare disease cause can be child’s play
    Families of rare disease patients are becoming increasingly creative in finding ways to fund much-needed research for rare disorders. Consider the Carol family. After their 13-year-old son was diagnosed with a rare form of leukaemia in 2006, the Carols got a first-hand look at the frustration the rare disease family typically endures in trying to find suitable diagnostics, treatment and management. The Carols were lucky: a donor was found for their son Taylor, who was able to be adequately treated by bone marrow transplantation. His condition is currently in remission. But the Carol family met and bonded with many other rare disease families during the course of Taylor’s illness, and decided to get active in raising money to help fund rare disease research.

    A playful solution

    The inspiration to capitalise on the popularity of computer games to raise money came to Jim Carol from watching his son. Video games furnished moments of respite and distraction for Taylor and other children during the often painful and monotonous routine of hospitalisation. Now, besides helping sick patients endure their disorder, video games are being taken one step further by being harnessed through a fund-raising opportunity. The Carols founded DonateGames, a charitable organisation that works by recycling used games that can be donated to the charity in exchange for a tax write-off. These games are then made available for purchase to other gamers at a lower price than they would cost brand-new. Since there are a large variety of video games on the market, targeting different ages, gender and interest, just about anyone can support the cause through game or cash donations, game purchases, or volunteer service. Although based in the USA, Donate Games accepts contributions through PayPal, and encourages participation from gaming communities around the world.

    DonateGames’ story also involves another rare disease patient – Duke University student Josh Sommer, diagnosed with a clival chordoma in 2006. Since his diagnosis and an initial surgical intervention, Josh has been working with a Duke University oncologist studying the genetic basis of chordoma. Josh has also co-founded the Chordoma Foundation with his mother, Dr. Simone Sommer, in addition to working with the Carols to establish DonateGames and serves as a spokesman for the organisation.

    DonateGames has a scientific committee that includes experts from the National Institutes of Health in the USA, who offer guidance to “identify and fund centres of scientific excellence and worthwhile endeavours that are dedicated to alleviating the pain and suffering of those afflicted with orphan diseases”. The committee has developed a set of criteria to determine which diseases, research and support organisations to fund. Chordoma, progeria, and Rett syndrome are amongst the rare disorders initially earmarked to receive proceeds from DonateGames.


    Courses & Educational Initiatives
    European School of Genetic Medicine - Spring Programme
    The European School of Genetic Medicine is offering several courses in the coming weeks and months, including:

  • The 22nd Course in Medical Genetics
  • The 9th Course in Genetic Counselling in Practice
  • The 5th Course in Statistical Genetic Analysis of Complex Phenotypes
  • For further details and the complete list of upcoming courses

    7th Summer School for Primary Immunodeficiency Diseases
    The seventh summer school for primary immunodeficiency diseases of the European Society for Immunodeficiencies is conducted by a leading faculty of experts who work at the forefront of clinical immunology, managing patients with the whole spectrum of primary immunodeficiency. The course presents an opportunity for attendees to network with colleagues. Three of the main topics this year will include T-cell disorders, hypogammaglobulinemia in children and adults, and innate immunity. The course will take place from 2-6 September 2009 in Bled, Slovenia.
    For further details


    What's on Where?
    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

    9th Congress of the Mediterranean Society of Myology
    Date: 20-22 March 2009
    Venue: Nicosia, Cyprus

    Facioscapulohumeral muscular dystrophy, mitochondrial myopathies, statins and acquired myopathies, laminopathies and cardiomyopathies, and update on therapeutic approaches are amongst the topics featured.
    For further details

    EC/ European Patients’ Forum Conference: How to move from agreed principles to good practice and positive change
    Date: 25 March 2009
    Venue: Brussels, Belgium

    This conference will facilitate the dissemination of the outcomes of the Pharmaceutical Forum initiative among European and national patients groups and the Health Community at large. The conference is primarily dedicated to patients groups either specialised in specific disease areas and/or representing patients at the local, national or European level. Representatives from the broader health community with an interest in the key areas addressed by the Pharmaceutical Forum are also very welcome.
    For further details

    International Meeting on Familial Lipodystrophies
    Date: 3-4 April 2009
    Venue: Santiago de Compostela, Spain

    Familial lipodystrophies are a group of rare diseases characterised by a loss of adipose tissue. Despite its low prevalence since 2000 an important number of papers have spread light upon its ethiopathogeny and pathophysiology. In this meeting some of the leading European experts in the field will come together to debate relevant questions related to both the clinical and molecular basis of these disorders.
    For further details

    International Society of Neonatal Screening: 6th European Regional Meeting
    Date: 26-28 April 2009
    Venue: Prague, Czech Republic

    Many interesting and relevant topics, such as Rare diseases and neonatal screening: Consensus building on neonatal screening based on the opinion of European Union patient support groups.
    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.
    For further details

    22nd Annual Meeting of the European Musculo-Skeletal Oncology Society
    Date: 13-16 May 2009
    Venue: Stuttgart, Gemany

    Including findings and research activities from the Sarcoma Groups of the German Society for Pediatric Oncology and Hematology. Session on rare bone and soft tissue tumours, and on paediatric and adolescent sarcomas.
    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.
    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.
    For further details

    First International Conference on Hyperphagia
    Date: 4-5 June 2009
    Venue: Baltimore, MD, USA

    Hyperphagia is the extreme unsatisfied drive to consume food which is a hallmark characteristic of Prader-Will syndrome and several other disorders, including Alstrom syndrome, WAGR syndrome, Fragile X syndrome and Laurence-Moon-Bardet-Biedl syndrome. This conference seeks to explore commonalties among affected rare diseases and open new doors of collaboration.
    For further details

    10th European Symposium: Prevention of Congenital Anomalies
    Date: 10 June 2009
    Venue: Bilbao, Spain

    Organised by EUROCAT and the Basque Government’s Ministry of Health, the symposium will share experience on the prevention of congenital anomalies and exhibit advances in prevention in different contexts. The main topics include environmental risk, prenatal diagnosis, and genetic counselling.
    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

    EuroGentest Symposium on Accreditation and Quality
    Date: 18-19 June 2009
    Venue: Leuven, Belgium

    Topics include: accreditation according to ISO 15189, accreditation bodies in Europe and the world, External Quality Assessment schemes, IT solutions to support your quality management system, and experiences from people working in an accredited laboratory or preparing for accreditation.
    For further details

    5th International Congress on Shwachman-Diamond Syndrome
    Date: 19-20 June 2009
    Venue: Amsterdam, Netherlands

    The 5th International Congress on Shwachman-Diamond Syndrome provides a unique opportunity for clinicians, researchers, and patient organisation representatives from around the world to meet.
    For further details

    Balkan Congress for Rare Diseases
    Date: 26-27 June 2009
    Venue: Cluj-Napoca, Romania

    This conference will address issues in diagnosing and managing rare diseases in the region and will explore ways to increase European collaboration.
    For further details

    Treatment Options in Phenylketonuria and Related Pediatric Neurotransmitter Disorders
    Date: 29 August 2009
    Venue: San Diego, California

    Key Topics include challenges in the pharmaceutical treatment of PKU and treatment of paediatric neurotransmitter disorders.
    For further details

    Genetics and Genomics of Vascular Disease Workshop
    Date: 13-16 September 2009
    Venue: Hyannis, MA

    The programme will present cutting edge research in areas like genome wide association studies in human populations, mouse QTL mapping of vascular phenotypes, and pathogenesis of vascular and developmental diseases using human patients and mouse models.
    For further details

    European Working Group on Rett Syndrome – 2009 Meeting
    Date: 17-18 September 2009
    Venue: Stresa, Italy

    An opportunity to discuss Rett syndrome-related science, to find collaborators for grant applications, and to exchange reagents and ideas. Moreover, the close contact with the parents associations should also help to focus better on the scientific problems that need to be resolved to find a cure for patients. Abstract deadline: 15 June 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

    Rare Diseases II: Hearing and Sight Loss
    Date: 22-27 November 2009
    Venue: Sant Feliu de Guixols, Spain

    Details to follow.
    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

    18th International Workshop on Vascular Anomalies
    Date: 21-24 April 2010
    Venue: Brussels, Belgium

    The programme for this workshop will be available soon.
    For further details


    Press & Publications
    Spina bifida: A new text promotes a multidisciplinary approach to management
    A newly published book promotes a multidisciplinary approach to spina bifida, providing the three main specialist categories involved - neurosurgeons, orthopaedic surgeons, and urologists - with an updated overview of surgical approaches and with a concise reference that explains the main clinical problems to be faced in everyday clinical practice. The evolution of technology has made new surgical techniques available for the treatment of diseases associated with the spina bifida malformation, and this is especially true in hydrocephalus and foetal surgery. The progress in this last field and in prenatal diagnosis have raised the significant problem of the effectiveness and usefulness of in utero surgical treatment of the malformation, that are extensively discussed in this volume. The clinical situations that can be seen in adolescents or young adults with spina bifida, including sexuality and pregnancy, are also highlighted.

    Spina Bifida: Management and Outcome
    Memete Özek, Guiseppe Cinalli, and Wirginia J. Maixner -eds
    Publisher: Springer
    ISBN: 978-88-470-0650-8


    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
    Contact Us
    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, Charlotte Rodwell, Claire Scharf-Kroener, Paloma Tejada, Aurélie Vandeputte
    National Contact Point: Jean Jacques Cassiman (Belgium), Rumen Stefanov (Bulgaria), Ana Stavljenic-Rukavina (Croatia), Violetta Anastasiadou (Cyprus), Milan Macek (Czech Republic), Andres Metspalu (Estonia), Riitta Salonen (Finland), Manfred Stuhrmann (Germany), Michael Petersen (Greece), János Sándor (Hungary), Andrew Green (Ireland), Judith Melki (Israel), Bruno Dallapiccola and Domenica Taruscio (Italy), Andre Megarbane (Lebanon), Vaidutis Kucinskas (Lithuania), Alfred Cuschieri (Malta), Abdelaziz Sefiani (Morocco), Martina Cornel (Netherlands), Stein Are Aksnes (Norway), Jolanta Sykut-Cegielska (Poland), Jorge Sequeiros (Portugal), Dragica Radojkovic (Serbia), Ludovit Kadasi (Slovakia), Borut Peterlin (Slovenia), Miguel del Campo and Manuel Posada de la Paz (Spain), Désirée Gavhed (Sweden), Loredana D'Amato Sizonenko (Switzerland), Habiba Chaabouni-Bouhamed (Tunisia), Fatmahan Atalar and Ugur Ozbek (Turkey), Edmund Jessop and Idoia Gomez-Paramio (United Kingdom)
    For more information on the Rare Diseases Task Force
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