28 February 2009 print
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28 February 2009: The Second International Rare Disease Day!

Saturday officially marks the Second International Rare Disease Day, but events have been unfolding all week and all around the world. OrphaNews Europe and the European Commission’s Rare Disease Task Force wish you an eventful and productive day and thank all the groups that are making an effort to put rare diseases on the agenda of topics that merit awareness, action and funding. From China to the Ukraine - and a hundred places in between - organisers are working hard to make this a day to remember! Visit the Rare Disease Day 2009 website to find activities in your area.

EU Policy News
Convention on Human Rights and Biomedicine: additional protocol adopted on genetic testing awaits Member State signatures
Within the Council of Europe Treaty Series, the Convention for the Protection of Human Rights and Dignity of the Human Being with Regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine (often referred to as the Oviedo Convention), signed by most of the European Member States, sets out the fundamental principles applicable in day-to-day medicine as well as those applicable to new technologies in human biology and medicine. An additional protocol to the Convention, concerning genetic testing for health purposes, was adopted by the Committee of Ministers in May 2008. To date signed by three member states (Finland, Luxembourg and Moldova), the Additional Protocol needs five ratifications (including four member states) to enter into force. The summary of the treaty states that the new protocol …sets down principles relating inter alia to the quality of genetic services, prior information and consent and genetic counselling. It lays down general rules on the conduct of genetic tests, and, for the first time at international level, deals with the directly accessible genetic tests for which a commercial offer could develop in future. It specifies the conditions in which tests may be carried out on persons not able to consent. Also covered are the protection of private life and the right to information collected through genetic testing. Finally, the Protocol touches on genetic screening.
Consult the Additional Protocol

Principles of care for haemophilia launched at European Parliament
The European Haemophilia Consortium (EHC) and the European Association for Haemophilia and Allied Disorders (EAHAD) officially launched a set of ten key principles for improving haemophilia care throughout the continent at a gathering taking place at the European Parliament in late January. The European Principles of Haemophilia Care, drafted by clinicians, nurses and patients, seeks to reduce existing disparities in the care patients receive across Europe. A central organisation for haemophilia care in each MS, access to prophylaxis treatment, national level patient registries, the management of inhibitors, home treatment, and increased education and research are amongst the topics outlined in the principles. Cooperation and the exchange of best practices are at the core of improved treatment. European- and national-level stakeholders are encouraged to establish “optimum standards of care across the 27 Member States and beyond”. In a press release, it is noted that the lack of adequate haemophilia treatment in some European countries “has dramatic consequences for patients and their families”. The EHC plans to monitor the implementation of the European principles of Haemophilia Care via several indicators. It is hoped that the adoption of these principles will create an impact that extends to other areas of the world and will also provide a basis for managing other rare conditions. The principles of sharing good practices and increasing collaboration are in alignment with recommendations issued from the European Commission, including the Communication on Rare Diseases: Facing Europe’s Challenge.
Consult the European Principles of Haemophilia Care (published in the journal Haemophilia)

Good news during hard times: EMEA reduces fees for orphan drug applications
At a moment when bad economic news dominates the headlines, a glimmer of good news emerges from the EMEA: Designated orphan medicinal products are now eligible for reductions for all fees payable under Community rules pursuant to amended Regulation (EEC) 2309/93. Covered in the reductions, applicable to orphan products designated in accordance with Regulation (EC) 141/2000, are the fees for pre-authorisation activities (protocol assistance such as scientific advice), as well as for products using the centralised procedure: the application for marketing authorisation, inspections, and post-authorisation activities. Taking effect 1 February 2009, the fee revisions reflect a policy of enhanced support for micro- small- and medium-sized enterprises (SMEs). Indeed, an EMEA press release states:
In the revised policy for 2009, the fee reduction for new applications for marketing authorisation to SMEs is increased to 100%. The fee reduction for post authorisation activities including annual fees to SMEs in the first year after granting a marketing authorisation is also increased to 100%. The 100% fee reduction for protocol assistance and 100% fee reduction for pre-authorisation inspections are maintained for all applicants. The 50% fee reduction for new applications for marketing authorisation submitted by applicants that are not SMEs is also maintained”.

The rare disease community is 100% pleased to learn of this development!

Consult the EMEA Public Statement on Fee Reductions for Designated Orphan Medicinal Products

EMEA recruiting in several areas
The European Medicines Agency is responsible for coordinating the evaluation and supervision of medicinal products for human and veterinary use in the European Union. The EMEA is currently organising selection procedures with a view to drawing up reserve lists for a number of positions including:

  • EMEA/AD/283: Administrator (Scientific), Unit for the Pre-Authorisation Evaluation of Medicines for Human Use, Safety and Efficacy Sector, and Scientific advice, Paediatrics and Orphan drugs Sector (AD5)
  • EMEA/AD/279: Administrator (Scientific), Pharmacovigilance and Risk Management, Unit for the Post-Authorisation Evaluation of Medicines for Human Use (AD6)
  • EMEA/AD/280: Administrator (Scientific), Pharmacovigilance and Risk Management, Unit for the Post-Authorisation Evaluation of Medicines for Human Use (AD8)
  • For further details


    National & International Policy Developments
    The Netherlands launches subsidy scheme to support orphan drug development
    The Dutch Steering Committee for Orphan Drugs in January launched an initiative designed to encourage translational research in the field of rare diseases. This new measure provides aid for Dutch pharmaceutical companies that have been officially designated as small- or medium-sized enterprises (SMEs) by the European Medicines Agency (EMEA). The funds are intended for Dutch SMEs to use toward the process of drafting and submitting their Orphan Designation Dossier (ODD) to the EMEA. The scheme is scheduled to run from January 2009 through November 2011 and consists of two types of subsidy – one for SMEs with ODD experience and one for those which are submitting their first ODD.
    Visit the website of the Dutch Steering Committee for Orphan Drugs

    Other European news
    CIBERER’s second annual meeting reviews progress made and considers future strategies in Spain

    The second annual meeting of the Centre for Biomedical Network Research on Rare Diseases (CIBERER) took place last November in Valencia, Spain. Launched in November 2006, CIBERER is the reference centre in Spain for research into rare disorders. A public consortium of some 30 institutions, the network has more than 700 professionals integrating 60 research groups, and is funded principally by the Spanish Ministry of Science and Innovation through the Carlos III Health Institute. The annual meeting provides members from each of the network’s seven distinct research areas to present progress and to voice any bottlenecks. This year’s reunion kicked off with an overview the network’s strategy from CIBERER Scientific Director Dr. Francesc Palau and Dr. José Jeronimo Navas Palacios, Director of the Carlos III Institut. The European policy on rare diseases was also highlighted by Antoni Monserrat of the DG Sanco. CIBERER is contributing its expertise toward the development of a national strategy for rare diseases in Spain. Amongst other sessions during the three-day event, a round table considered the challenge of translating research into clinical practice. To learn more about CIBERER, read the feature article that appeared in the 21 November 2007 issue of OrphaNews Europe.


    Ethical, Legal & Social Issues
    To disclose or not to disclose…that is the question concerning carrier status identified incidentally via newborn screening
    Newborn screening is available in many countries for an array of diseases – all of which are rare. Two recent articles considering the impact of disclosing carrier status identified through newborn screening reveal the lack of a cohesive policy on this issue. One article, published in the Journal of Genetic Counseling, reviews the effect of disclosing carrier status generated incidentally via newborn screening for cystic fibrosis and sickle cell anaemia, two diseases that are rare in certain populations and less so in others, and which are included in routine newborn screening programmes in some countries. The systematic examination undertaken by the researchers revealed the degree to which this issue is under-explored and the lack of empiric research necessary in order to develop appropriate polices. The authors suggest that genetic counsellors, as “key players in the management of these results”, are “well positioned to engage in formative research”. The second article, appearing in the February 2009 issue of the American Journal of Public Health, evokes the polar positions of withholding information versus requiring its disclosure. The authors (two of whom contributed to the first article) question the “routine disclosure of carrier status to avoid the taint of paternalism” and suggest that the “euphemism of withholding operates without consideration of the legal and practical realities of newborn screening as a public health intervention—realities that suggest the relevance of a corollary euphemism of requiring. Viewed from this perspective, other infringements on individual rights are apparent, arising from the potential right not to know information whose primary function is to identify reproductive risks and from the potential discord between the rights of infants and of their parents regarding this knowledge”. Acknowledging that this interpretation may be disputed by some, the authors welcome debate on the subject, concluding that “…an end to the apparent consensus about the value of generating and the necessity of disclosing incidental carrier results will provide welcome evidence that the public health ethics of newborn screening is receiving full attention”.
    Consult the PubMed abstracts:
    A Systematic Review of the Effects of Disclosing Carrier Results Generated Through Newborn Screening

    Questioning the Consensus: Managing Carrier Status Results Generated by Newborn Screening


    Orphanet News
    New Texts
    New Orphanet Journal of Rare Diseases publications
    Tetralogy of Fallot
    Amyotrophic lateral sclerosis
    Distal Xq duplication and functional Xq disomy
    Corneal dystrophies


    New Syndromes
    Familial pulmonary arterial hypertension, leucopenia, and atrial septal defect: a probable new familial syndrome
    The authors present two siblings with identical clinical findings. Major findings involve pulmonary arterial hypertension, cardiac abnormalities including secundum-type atrial septal defect, and intermittent neutropenia, lymphopenia, monocytosis, and anaemia. The siblings also share several minor abnormalities: pectus carinatum, long fingers, proximally placed thumb, broad nasal bridge, and high-arched palate. The male proband also had bilateral inguinal hernias and undescended testes. Investigations revealed a bone morphogenetic protein receptor 2 polymorphism in intron 4 in only one sibling, which was also present in unaffected maternal relatives.
    Read the PubMed abstract

    Clin Dysmorphol ; 19-23 ; January 2009
    Anterior segment anomalies of the eye, growth retardation associated with pituitary gland and endocrine abnormalities
    The authors report on two siblings from an inbred Arab family with anterior segment anomalies of the eyes, and growth retardation associated with small pituitary gland and endocrine abnormalities. Similar to Peters-plus syndrome, this new entity has in addition small pituitary gland associated with growth hormone. In addition, sequencing of the B3GALTL gene implicated in Peters-plus syndrome did not reveal any mutation. The association of anterior segment anomalies of the eye, growth retardation, and endocrine problems was described by Jung et al in 1995. The features in the children in this report could represent a variable manifestation of this syndrome or a previously undescribed syndrome.
    Read the PubMed abstract

    Am J Med Genet A ; 251-256 ; 15 January 2009
    Recessive developmental delay, small stature, microcephaly and brain calcifications with locus on chromosome 2
    Two interrelated Omani families are described with eight children manifesting a genetic disorder with widespread brain calcifications. Brain imaging showed extensive scattered calcifications of basal ganglia and cortex, suggesting possible Aicardi-Goutieres syndrome (AGS) or Coats-plus syndrome. However, the clinical features in the present families diverge substantially from these two conditions. Growth delay, mild developmental delay, and poor school performance were present in all affected individuals, but progressive deterioration of neurological function was not apparent, nor were there significant cortical white matter disease or retinopathy. Genome-wide linkage and fine-mapping analyses of the extended family members and affected individuals indicate a genetic locus for this disorder on Chromosome 2.
    Read the PubMed abstract

    Am J Med Genet A ; 129-137 ; 15 January 2009

    New Genes
    Cerebrocostomandibular-like syndrome and a mutation in the conserved oligomeric Golgi complex, subunit 1
    The authors describe two patients with a cerebrocostomandibular-like syndrome and a novel mutation in the gene COG1, involved in retrograde vesicular trafficking and glycosylation. Cerebrocostomandibular syndrome itself is heterogeneous as both autosomal dominant and autosomal recessive inheritance have been described. Further genetic heterogeneity is expected as no mutations in COG1 were found in two additional patients with a cerebrocostomandibular syndrome.
    Read the PubMed abstract

    To read more about "Cerebro-costo-mandibular syndrome"

    Hum Mol Genet ; 517-524 ; 1 February 2009
    cblF defect of vitamin B12 metabolism: identification of a putative lysosomal cobalamin exporter altered
    Vitamin B(12) (cobalamin) is essential in animals for metabolism of branched chain amino acids and odd chain fatty acids, and for remethylation of homocysteine to methionine. In the cblF inborn error of vitamin B(12) metabolism, free vitamin accumulates in lysosomes, thus hindering its conversion to cofactors. Using homozygosity mapping in 12 unrelated cblF individuals and microcell-mediated chromosome transfer, the authors identified a candidate gene, LMBRD1, encoding a lysosomal membrane.
    Read the PubMed abstract

    To read more about "Methylmalonicacidemia - homocystinuria, type cbl F"

    Nat Genet ; 234-239 ; February 2009
    Marie Unna hereditary hypotrichosis: loss-of-function mutations of an inhibitory upstream ORF in the human hairless transcript
    Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant form of genetic hair loss. In a large Chinese family carrying MUHH, the authors identified a pathogenic initiation codon mutation in U2HR, an inhibitory upstream ORF in the 5’ UTR of the gene encoding the human hairless homolog (HR). In 18 more families from different ancestral groups, they identified a range of defects in U2HR.
    Read the PubMed abstract

    To read more about "Marie Unna congenital hypotrichosis"

    Nat Genet ; 228-233 ; February 2009
    Perry syndrome: DCTN1 mutations
    Perry syndrome consists of early-onset parkinsonism, depression, severe weight loss and hypoventilation, with brain pathology characterised by TDP-43 immunostaining. The authors carried out genome-wide linkage analysis and identified five disease-segregating mutations affecting the CAP-Gly domain of dynactin (encoded by DCTN1) in eight families with Perry syndrome; these mutations diminish microtubule binding and lead to intracytoplasmic inclusions.
    Read the PubMed abstract

    Nat Genet ; 163-165 ; February 2009

    Research in Action
    Fundamental Research
    Pseudoxanthoma elasticum is a metabolic disease
    Pseudoxanthoma elasticum (PXE) is a pleiotropic multisystem disorder affecting skin, eyes, and the cardiovascular system with progressive pathological mineralisation. It is caused by mutations in the ABCC6 gene expressed primarily in the liver and kidneys, and at very low levels, if at all, in tissues affected by PXE. A question has arisen regarding the pathomechanism of PXE, particularly the "metabolic" versus the "PXE cell" hypotheses. The authors examined a murine PXE model by transplanting muzzle skin from knockout (KO) and wild-type (WT) mice onto the back of WT and KO mice using mineralisation of the connective tissue capsule surrounding the vibrissae as an early phenotypic biomarker. Grafting of WT mouse muzzle skin onto the back of KO mice resulted in mineralisation of vibrissae, whereas grafting KO mouse muzzle skin onto WT mice did not. These findings implicate circulatory factors as a critical component of the mineralisation process. This mouse grafting model supports the notion that PXE is a systemic metabolic disorder with secondary mineralisation of connective tissues.
    Read the PubMed abstract

    To read more about "Pseudoxanthoma elasticum"

    J Invest Dermatol ; 348-354 ; February 2009
    Clinical Research
    Neuro-Behçet disease: epidemiology, clinical characteristics, and management
    Behçet disease (BD) is a multisystem relapsing inflammatory disorder of unknown cause. In neuro-BD (NBD), the CNS can be involved in one or both of two ways: first, and most commonly, through the development of an immune-mediated meningoencephalitis, which predominantly involves the brainstem, but can also involve the basal ganglia, thalamus, cortex and white matter, spinal cord, or cranial nerves; and second, as a consequence of thrombosis within the dural venous sinuses. Collaborative prospective studies of the natural history of the disease, particularly the nature and treatment of progressive neurological disease, and evidence-based studies of treatment are needed.
    Read the PubMed abstract

    To read more about "Behcet disease"

    Lancet Neurol ; 192-204 ; February 2009
    Osteogenesis imperfecta type II: mutation and polymorphism spectrum and implications for genotype-phenotype relationships
    Osteosis imperfecta (OI), also known as brittle bone disease, is a clinically and genetically heterogeneous disorder primarily characterised by susceptibility to fracture. Although OI generally results from mutations in the type I collagen genes, COL1A1 and COL1A2, the relationship between genotype and phenotype is not yet well understood. To provide additional data for genotype-phenotype analyses and to determine the proportion of mutations in the type I collagen genes among subjects with lethal forms of OI, the authors sequenced the coding and exon-flanking regions of COL1A1 and COL1A2 in a cohort of 63 subjects with OI type II, the perinatal lethal form of the disease. They identified 61 distinct heterozygous mutations in type I collagen, including five non-synonymous rare variants of unknown significance, of which 43 had not been seen previously.
    Read the PubMed abstract

    To read more about "Osteogenesis imperfecta"

    Hum Mol Genet ; 463-473 ; 1 February 2009
    RECQL4 diseases: the mutation spectrum
    Mutations in the RECQL4 gene can lead to three clinical phenotypes with overlapping features. All these syndromes, Rothmund-Thomson (RTS), Rapadilino and Baller-Gerold (BGS), are characterised by growth retardation and radial defects, but Rapadilino syndrome lacks the main dermal manifestation, poikiloderma, which is a hallmark feature in both RTS and BGS. It has been previously shown that RTS patients with RECQL4 mutations are at increased risk of osteosarcoma, but the precise incidence of cancer in Rapadilino and BGS has not been determined. The authors summarise all the published RECQL4 mutations and their associated cancer cases and provide an update of 14 novel RECQL4 mutations with accompanying clinical data.
    Read the PubMed abstract

    To read more about "Baller-Gerold syndrome"
    To read more about "RAPADILINO syndrome"
    To read more about "Rothmund-Thomson syndrome"

    Eur J Hum Genet ; 151-158 ; February 2009
    Hereditary spastic paraplegia: expansion of genetic and phenotypic characteristics
    The SPAST gene encoding for spastin plays a central role in the genetically heterogeneous group of diseases termed hereditary spastic paraplegia (HSP). In this study, the authors expand and refine the genetic and phenotypic characteristics of SPAST-associated HSP by examining a large cohort of HSP patients/families. Screening of 200 unrelated HSP cases for mutations in the SPAST gene led to detection of mutations in 57 patients (28.5%), of which 47 were distinct and 29 were novel mutations. Their data also suggest a tentative genotype-phenotype correlation and indicate that the missense mutations could cause an earlier onset of the disease.
    Read the PubMed abstract

    Eur J Hum Genet ; 187-194 ; February 2009
    von Willebrand disease type 2B: clinical and molecular predictors of thrombocytopenia and risk of bleeding in patients
    Type 2B von Willebrand disease (VWD2B) is caused by an abnormal von Willebrand factor (VWF) with increased affinity for the platelet receptor glycoprotein Ib-alpha (GPIb-alpha) that may result in moderate to severe thrombocytopenia. The authors evaluated the prevalence and clinical and molecular predictors of thrombocytopenia in a cohort of 67 VWD2B patients from 38 unrelated families characterised by VWF mutations. Thrombocytopenia was found in 20 patients at baseline and in 38 after stress conditions. The risk of bleeding was higher in patients with thrombocytopenia and in those with the highest tertile of bleeding severity score.
    Read the PubMed abstract

    To read more about "Von Willebrand disease, type 2B"

    Blood ; 526-534 ; 15 January 2009
    Mediterranean fever: a comparative study of disease severity in children and adolescents explores environmental factors
    Worldwide, familial Mediterranean fever (FMF) is the most common autoinflammatory disease. It has been suggested that environmental factors affect the phenotype as some patients do not develop the complication of secondary amyloidosis. A total of 55 Turkish children living in Turkey were compared with 45 Turkish children born and raised in Germany. M694V was the leading genetic mutation in both groups. 78.2% of patients from the group living in Turkey had a severe course compared with 34.1% from the group living in Germany. These results suggest that the environment affects the phenotype of a monogenic disease of the innate inflammatory pathway.
    Read the PubMed abstract

    To read more about "Familial mediterranean fever"

    Ann Rheum Dis ; 246-248 ; February 2009
    Stem Cells
    Spinal muscular atrophy: induced pluripotent stem cells from a patient
    Spinal muscular atrophy is one of the most common inherited forms of neurological disease leading to infant mortality. Patients have selective loss of lower motor neurons resulting in muscle weakness, paralysis and often death. Here the authors report the generation of induced pluripotent stem cells from skin fibroblast samples taken from a child with spinal muscular atrophy. These cells expanded robustly in culture, maintained the disease genotype and generated motor neurons that showed selective deficits compared to those derived from the child’s unaffected mother. This is the first study to show that human induced pluripotent stem cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen new drug compounds and develop new therapies.
    Read the PubMed abstract

    To read more about "Proximal spinal muscular atrophy, type 1"

    Nature ; 277-280 ; 15 January 2009
    Gene Therapy
    Haemophilia B: long-term correction of inhibitor-prone dogs treated with liver-directed AAV2-mediated factor IX gene therapy
    Preclinical studies and initial clinical trials have documented the feasibility of adenoassociated virus (AAV)-mediated gene therapy for haemophilia B. In an 8-year study, inhibitor-prone haemophilia B dogs treated with liver-directed AAV2 factor IX (FIX) gene therapy did not have a single bleed requiring FIX replacement, whereas dogs undergoing muscle-directed gene therapy had a bleed frequency similar to untreated FIX-deficient dogs.
    Read the PubMed abstract

    To read more about "Hemophilia B"

    Blood ; 797-806 ; 22 January 2009
    Therapeutic Approaches
    Waldenstrom macroglobulinemia: Endoplasmic reticulum stress is a target for therapy
    Waldenstrom macroglobulinemia (WM) is an incurable low-grade lymphoma characterised by bone marrow (BM) involvement of IgM secreting lymphoplasmacytic cells. The authors examined tunicamycin, endoplasmic reticulum stress inducer, for potential antitumour effects in WM. Tunicamycin induced significant cytotoxicity, apoptosis and cell-cycle arrest, and inhibited DNA synthesis in WM cell lines and primary BM CD19(+) cells from patients with WM but not in healthy donor cells. Importantly, coculture of WM cells in the context of the BM microenvironment did not inhibit tunicamycin-induced cytotoxicity.
    Read the PubMed abstract

    To read more about "Waldenström macroglobulinemia"

    Blood ; 626-634 ; 15 January 2009
    Spinal muscular atrophy: survival motor neuron gene 2 silencing by DNA methylation correlates with disease severity
    Spinal muscular atrophy (SMA), a common neuromuscular disorder, is caused by homozygous absence of the survival motor neuron gene 1 (SMN1), while the disease severity is mainly influenced by the number of SMN2 gene copies. This correlation is not absolute, suggesting the existence of yet unknown factors modulating disease progression. The authors demonstrate that the SMN2 gene is subject to gene silencing by DNA methylation. DNA methylation is functionally important regarding SMA disease progression and pharmacological SMN2 gene activation which might have implications for future SMA therapy regimens.
    Read the PubMed abstract

    To read more about "Proximal spinal muscular atrophy"

    Hum Mol Genet ; 304-317 ; 15 January 2009

    Patient Management and Therapy
    Long-QT syndrome type 1: contribution of noncompliance and QT-prolonging drugs to beta-blocker treatment
    Beta-Blocker efficacy in long-QT syndrome type 1 is good but variably reported, and the causes of cardiac events despite beta-blocker therapy have not been ascertained. In this retrospective study involving 216 patients over a 10 year period, the authors determined that beta-blocker noncompliance and use of QT-prolonging drug are responsible for almost all life-threatening "beta-blocker failures." Beta-Blockers are appropriate therapy for asymptomatic patients and those who have never had a cardiac arrest or beta-blocker therapy. Routine implantation of cardiac defibrillators in such patients does not appear justified.
    Read the PubMed abstract

    To read more about "Romano-Ward long QT syndrome"

    Circulation ; 215-221 ; 20 January 2009
    Tetralogy of Fallot: Pulmonary valve replacement impact on survival and ventricular tachycardia
    Pulmonary valve replacement (PVR) in repaired tetralogy of Fallot (TOF) reduces pulmonary regurgitation and decreases right ventricular (RV) dilation, but its long-term impact on ventricular tachycardia (VT) and mortality is unknown. This study aimed to determine the incidence of death and VT in TOF after PVR and to test the hypothesis that PVR leads to improvement in these outcomes. A total of 98 patients with TOF and late PVR for RV dilation were identified. Matched control subjects were identified for 77 of these patients; control subjects had TOF with RV dilation but no PVR. In the PVR group, 13 events occurred over 272 patient-years. No significant change in QRS duration was seen for any group. Overall 5- and 10-year freedom from death, VT, or both was 80% and 41%, respectively. In the matched comparison, no significant differences were seen in VT, death, or combined VT and/or death. This cohort experienced either VT or death every 20 patient-years.
    Read the PubMed abstract

    To read more about "Tetralogy of Fallot"

    Circulation ; 445-451 ; 27 January 2009
    Chronic inflammatory demyelinating polyradiculoneuropathy: methotrexate showed no significant benefit
    Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) responds to treatment with corticosteroids, intravenous immunoglobulin, and plasma exchange. The authors aimed to test whether the standard immunosuppressive drug methotrexate was of use in treatment of CIDP via a pilot, multicentre, randomised, double-blind, controlled trial comparing oral methotrexate 7.5 mg weekly for 4 weeks, then 10 mg weekly for 4 weeks, and finally 15 mg weekly for 32 weeks with placebo in patients with CIDP requiring intravenous immunoglobulin or corticosteroids. Oral methotrexate 15 mg weekly showed no significant benefit, but limitations in the trial design and a high rate of response in the placebo group mean that a treatment effect could not be excluded.
    Read the PubMed abstract

    To read more about "Chronic inflammatory demyelinating polyneuropathy"

    Lancet Neurol ; 158-164 ; February 2009
    Waldenstrom macroglobulinemia: long-term survival in 10-year trial follow-up
    The survival of patients with Waldenstrom macroglobulinemia (WM) varies enormously. The development of prognostic models in WM has been fraught by limited follow-up in current studies. Here, the authors update the outcome of a prospective WM trial with a median follow-up of 10 years for live patients. Of the 59 previously untreated patients who initially were observed, only 12 patients required therapy at a median follow-up of 100 months. Multivariate analysis among the 183 patients requiring therapy reaffirmed age 70 years or greater, previous nonprotocol therapy, and beta-2 microglobulin (B2M) of 3 mg/dL or greater as prognostic factors. Importantly, increased serum lactate dehydrogenase (LDH) was identified as an additional independent variable, which improved risk assessment beyond the recent WM international prognostic scoring system. The authors identified 3 risk groups with 8-year survival estimates of 55%, 33%, and 5%. These data provide novel insights into factors predicting long-term outcome in WM.
    Read the PubMed abstract

    To read more about "Waldenström macroglobulinemia"

    Blood ; 793-796 ; 22 January 2009
    Huntington disease: long-term outcome of presymptomatic testing
    This cross-sectional study on long-term outcome of presymptomatic testing for Huntington disease had two aims: the comparison of the psychological well-being and social adjustment of carriers and non-carriers of the mutation, and the identification of psychological determinants to improve care/support of testees. A structured interview including five self-report scales and the Mini International Neuropsychiatric Inventory was proposed to detect a psychopathology or problem with social adjustment. The authors interviewed 119 testees (53%), 62 non-carriers and 57 carriers after a mean delay of 3.7 years after their result. Depression was frequent in asymptomatic carriers (58%). Interestingly, the self reported impact of the test showed that 27% of non-carriers did not cope well with a favourable result, and a significant percentage of non-carriers (24%) were depressed during follow-up. Multivariate analysis showed that only a previous episode of depression was predictive of depression after genetic testing in both carriers and non-carriers of the HD mutation. Psychological support is necessary for all testees regardless of the result of their presymptomatic test, because psychiatric care is often needed by both carriers and non-carriers.
    Read the PubMed abstract

    To read more about "Huntington disease"

    Eur J Hum Genet ; 165-171 ; February 2009

    Orphan Drugs
    First FDA approved biologic from genetically engineered animals is for a rare disorder: hereditary antithrombin deficiency
    The U.S. Food and Drug Administration has approved ATryn (antithrombin alfa), an anticoagulant used to prevent blood clots in patients with hereditary antithrombin deficiency. ATryn is the first biological product produced from genetically engineered animals to be approved in the USA. ATryn, derived from goats that have been genetically engineered to produce human antithrombin in their milk, received marketing authorisation in Europe in July 2006. In the USA, ATryn is manufactured by GTC Biotherapeutics.
    Children given priority during Myozyme supply shortage
    The European Medicines Agency’s (EMEA) Committee for Medicinal Products (CHMP) has recommended that infants, children and adolescents be given priority access to Myozyme (alglucosidase alfa) during a shortage of the medicine expected over the next few months. The recommendation ensures that paediatric patients will continue to receive Myozyme until manufacturer Genzyme Corp. resolves the problem. Myozyme is used to treat patients with Pompe disease, a rare, inherited enzyme-deficiency disorder. Pompe disease leads to a progressive build-up of glycogen in certain tissues, particularly the heart and other muscles, causing a wide range of problems, including an enlarged heart, breathing difficulties and muscle weakness. Early onset of the disease is characterised by rapid progression and is usually fatal without treatment. Adult onset progresses slower and is typically less life-threatening. According to an EMEA press release, the current shortage in product is caused by the “demand for Myozyme outgrowing current manufacturing capacity, as well as problems with the manufacture of the medicine at some sites”.
    Consult the press release for the specific details of the CHMP recommendation


    News from the Patients' Associations
    A growing number of free online tools are available to help nonprofit organisations
    Patient groups and other champions of the rare disease cause are increasingly taking advantage of free online tools designed to help non-profit organisations connect, increase awareness, and raise funds. In 2007, YouTube, the popular free online video website, launched its Nonprofit Program. It is intended to allow organisations a free venue in the form of a designated nonprofit video to communicate with members, supporters, volunteers, and donors, and to air the organisation’s needs. When used in tandem with Google’s Checkout "Donate" button (Google acquired YouTube in 2006) donations can be made directly from the YouTube site. Google for Non-Profits offers an array of tools designed to help organisations campaign, raise money, and function more efficiently: Google Analytics is designed to help groups better understand how users interact with their website, allowing sites to improve design and “turn more visitors into donors”; The Google Apps Education Edition allows patient organisations to launch a site inexpensively, "without a dedicated IT staff" onboard. The USA’s March of Dimes and UK-based rare chromosome disorder organisation Unique are amongst the growing number of groups using the new services. Available in the USA and UK for the moment, YouTube is planning on extending its Nonprofit Program to other countries.

    Courses & Educational Initiatives
    Orphan Europe Academy 2009 Rare Disease Education Programme available
    The Orphan Europe Academy has several courses specific to rare diseases for health professionals in its 2009 programme:

  • Neurological manifestations of metabolic disorders course:
    7-9 May 2009, In partnership with the Sant Joan de Déu Hospital, Barcelona (Spain)
  • 2nd Practical training in metabolic diseases affecting the liver course:
    24-27 June 2009, In partnership with the Jeanne de Flandre Hospital, Lille (France)
  • 3rd Inborn errors in neonatology course:
    30 September-2 October 2009, In partnership with the Charles University Prague, (Czech Republic)
  • 8th European metabolic course:
    3-7 November 2009, In partnership with Radboud University Nijmegen Medical Centre, Nijmegen (Belgium)
  • 2nd European adult metabolic course:
    27-30 January 2010, In partnership with the Pitié-Salpêtrière Hospital, Paris (France)

  • For further details and registration


    What's on Where?
    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

    9th Congress of the Mediterranean Society of Myology
    Date: March 20-22 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

    International Meeting on Familial Lipodystrophies
    Date: 3-4 April 2009 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

    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.
    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

    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. Extended submission deadline for abstracts: 1 March, 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

    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 this region and will explore ways to increase European collaboration.
    For further details

    Treatment Options in Phenylketonuria and Related Pediatric Neurotransmitter Disorders
    Date: 29 August 29 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

    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

    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
    Delving into the double helix: a new book traces the development of genetic screening
    Science historian and sociologist Ruth Schwartz Cowan offers the reader an account of the history of genetic screening. From its early development, when the field of genetic medicine was nearly compromised by the parallel practice of eugenics, Heredity and Hope: The Case for Genetic Screening brings us forward to the present day, to examine many of the difficult issues that the various stakeholders – doctors, patients, parents, legislators, business leaders, and citizens – must grapple with. The author traces the development of screening for several hereditary diseases – including Tay-Sachs disease and phenylketonuria – and confronts some of the criticisms these programmes have received over the years. A separate chapter of the book considers the case of Cyprus, where the only mandatory premarital genetic screening policy in the world exists (for the genetic defect that causes beta-thalassemia). The author, arguing that pre-and post-natal genetic screening is “morally right and politically acceptable” is herself a recipient of amniocentesis testing. It is thus from personal experience that she that evokes the existential questions the choice of whether or not to undergo genetic testing can awaken:

    We must think deeply about our most intimate, emotion-laden relationships, the ones we usually push to the back of our consciousness just to be able to get through the day: relationships between sexual partners, between spouses, between parents and children. The decisions we make about genetic testing depend on our answers to questions on which even philosophers and theologians disagree. What is a good life? What is a good parent? What is good health—and how important is it? What does it really mean to love a foetus, a child, a spouse, yourself? ...Of course these are not just personal questions; they are social and political questions as well.

    Arguing that quality of life can be vastly improved via the responsible use of genetic screening, the book nonetheless calls for the development of guidelines that will help navigate decision-making processes inherently involved in genetic testing.

    Heredity and Hope: The Case for Genetic Screening
    Ruth Schwartz Cowan
    Harvard University Press 2008
    ISBN 13: 978-0-674-02424-3


    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, Ewa Pronicka, Claire Scharf-Kroener, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
    For more information on the Rare Diseases Task Force
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