4 February 2009 print
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A new joint action will support the Rare Diseases Task Force and contribute to the revision of the ICD for rare disorders

The European Commission Directorate General Public Health (DG Sanco) has elected to fund a joint action between the Czech Republic, France, Italy, the Netherlands, and the United Kingdom, supporting the Rare Disease Task Force scientific activities for the next three years. The overarching objective is to provide analysis and technical assistance supporting the development and implementation of a policy in the area of rare diseases and orphan drugs. This includes scientific support for the activities of the Rare Diseases Task Force (RDTF) by identifying existing documentable indicators relevant to rare diseases and collecting relevant data on a yearly basis; disseminating political and scientific developments to all stakeholders through ad hoc reports and OrphaNews Europe, including information on national and EU initiatives and incentives; liaising between EU agencies and services and major stakeholders to enhance collaboration and maximise input and outcomes; and providing assistance to the RDTF on other scientific issues that may be identified in the course of this project. Another major objective involves improving the traceability of rare diseases in health information systems by assigning International Classification of Diseases codes (ICD10) to all rare diseases; proposing changes to improve the classification in view of the future adoption of the ICD11 using the technical platform developed by the World Health Organization; cross-referencing with other classification systems such as MedDRA and SNOMED-CT, and posting this information on the Orphanet website, in a format adapted to the needs of the information system community to maximise its use. We will keep you regularly informed of progress made in accomplishing these important goals.

Spotlight on...
Orphanet’s new country coordinator is bringing rare disorders out of isolation in Greece
Dr. Michael B. Petersen, Director of the Department of Genetics at the Institute of Child Health, Athens, Greece, studied Medicine at the University of Copenhagen and subsequently specialised in Clinical Genetics. He went on to complete a postdoctoral Fulbright fellowship in Molecular Genetics at the Center for Medical Genetics, Johns Hopkins University School of Medicine. From 1993 Dr. Petersen has served as Director in the Department of Genetics at the Institute of Child Health, in Athens, Greece. His principle research interest encompasses the origin and mechanisms of chromosomal aneuploidies. In recent years Dr. Petersen has concentrated on monogenic disorders of deafness and blindness. He has published more than 150 articles in peer-reviewed international genetics journals. Last year, Dr. Petersen also agreed to serve as Orphanet coordinator for the country of Greece. OrphaNews Europe took the opportunity to learn more about Dr. Petersen’s activities in the field of rare diseases in Greece.

OrphaNews Europe: One of your recent publications (Am J Med Gen Part A 2008;146A: 2221-2226) presents a fascinating study of Cohen syndrome in an isolated Greek island population. Could you tell us more about this study?

Dr. Petersen: It was known for decades that in this small isolated island population (around 2,000 inhabitants) there was an increased frequency of mental retardation. So, ten years ago we started to travel to these remote islands, as the patients very rarely come to mainland Greece for medical care. We understood that we were dealing with a syndromic form of mental retardation segregating as an autosomal recessive trait. Nearly all 15 affected individuals could be assigned to one huge pedigree and we were obviously dealing with a high degree of consanguinity. Blood samples were drawn from all family members and, with the help of Italian colleagues, we realized that we were probably dealing with Cohen syndrome. Soon after this, the genetic defect (COH1 gene mutation) was discovered, so that we can now offer both carrier testing and prenatal diagnosis. It has been a big accomplishment and a source of immense satisfaction to be able to help this isolated population with a severe health problem.

OrphaNews Europe: How do inhabitants in an isolated area cope with the manifestations of the disease?

Dr. Petersen: The majority of this population is occupied as fishermen and sailors. Most patients are severely affected and taken care of by their families in their own homes. They rarely come to nearby, bigger islands for proper medical attention. For this reason, we have planned a trip to the islands this spring together with an ophthalmologist, so that the patients can have an eye exam (for many of them for the first time in their life). In the early years, it was not easy to get access to the families, but in more recent years we see a big change, and we are now accepted by these families.

OrphaNews Europe: Has your study led to carrier screening in this population?

Dr. Petersen: We have so far analysed about 200 samples of individuals from the affected families. This has thus far been accomplished in collaboration with the IRCCS Neurological Institute “C. Besta”, Milan, on a research basis. We have estimated that we need to screen 1,000 individuals of child-bearing age and we have applied for funding to do this from the Ministry of the Aegean Sea.

OrphaNews Europe: With more than 200 of the total 6000 Greek islands inhabited (of which over 80 have populations of more than 100 persons), might other islands have founder migrations? Does the unique archipelago geography contribute to an increased number of rare monogenic conditions in Greece?

Dr. Petersen: This is indeed possible, though the subject has not been extensively studied. Another known example in Greece is Naxos disease, an autosomal recessive disorder characterised by palmoplantar keratoderma and arrhytmogenic right ventricular failure. Founder migrations, such as the ‘Finnish disorders’ for example, are well-known phenomena in several places around the world.

OrphaNews Europe: Greece is currently developing a national plan for rare diseases. Could you give us some details on this plan?

Dr. Petersen: One important goal of the National Plan of Action for Rare Disorders 2008-2012 is the improvement of the quality of services involved in the diagnosis and therapy of patients with rare disorders.

OrphaNews Europe: Will the Greek plan have to take into account its unique geography and the potential for rare autosomal recessive disorders amongst its more isolated populations?

Dr. Petersen: This is a very interesting idea, that I do not think anyone has ever looked at, but which could obviously be addressed through the planned National Registry of Rare Disorders.

OrphaNews Europe: What is the current policy in Greece for providing treatment for rare disorders?

Dr. Petersen: Greece wants to follow the European guidelines for rare disorders and is working for better access to treatment of rare disorders, including accreditation to referral centres for rare disorders. The goal of the Greek Ministry of Health is to improve the access of the patients to orphan drugs, including reimbursement from the public insurance system.
Read the full interview with Dr. Petersen


EU Policy News
Dates are provisionally set for each step of the adoption of the European Council rare disease recommendation
The European Commission on 11 November adopted a Communication and a proposal for a Council Recommendation on rare diseases that delineate a strategy supporting Member States in diagnosing, treating and caring for citizens with rare diseases. At the request of the Council, the Committee of Regions, the European Economic and Social Committee, and the Parliament have agreed to consult the Recommendation. Dates have now been set for each entity to return their opinion on the document. The Committee of Regions is scheduled to present its opinion at a plenary session scheduled for 11-12 February 2009; the European Economic and Social Committee is scheduled to present its opinion at a plenary session scheduled for 25-26 February; and the Parliament is scheduled to present its opinion at a plenary session scheduled for 23-26 March. The meeting of the Council of Ministers for adoption of the documents is scheduled for 9 June 2009.
Consult the Proposal for a Council Recommendation for a European Action in the Field of Rare Diseases (available in 22 languages)

Document on orphan designation now open for public consultation
The European Medicines Agency’s Committee for Orphan Medicinal Products (COMP) has drafted a document for public consultation. The document, entitled Recommendation on elements required to support the medical plausibility and the assumption of significant benefit for an orphan designation (EMEA/COMP/15893/2009) is a revision of the ‘Guideline on elements required to support the medical plausibility and the assumption of significant benefit for an orphan designation’ (EMEA/COMP/66972/2004), released in September 2004, which has now been superseded. Comments may be sent to the EMEA up until 21 July 2009, by e-mail. The EMEA and the European Commission plan to perform a revision exercise of the currently existing documents that give advice on different aspects related to orphan designation.
EMEA inaugurates a new scientific committee: CAT will review advanced therapy products
The European Medicines Agency (EMEA) has announced the formation of the Committee for Advanced Therapies (CAT) – the EMEA’s sixth scientific committee. Created following new European Union legislation concerning the regulation of advanced-therapy medicinal products, the CAT met for the first time on 15 January 2009. Three types of advanced therapy products are defined in the EU legislation: gene therapy products, somatic cell therapy products and tissue engineered products. Similar to the COMP, the CAT will “prepare a draft opinion on each advanced-therapy medicinal product submitted to the EMEA for evaluation as part of a marketing-authorisation application, prior to the adoption of a final opinion by the Committee for Medicinal Products for Human Use (CHMP), which retains overall responsibility for scientific evaluation of human medicines at the EMEA”. As advanced medical technologies are of particular interest to the rare disease community, OrphaNews Europe is adding the CAT to its list of agencies which are monitored closely and reported on regularly. Learn more about the CAT

National & International Policy Developments
In the USA rare diseases receive fast-track status for disability aid
In October 2008, the United States Social Security Administration (SSA) launched the Compassionate Allowances initiative, designed to facilitate the rapid extension of benefits to applicants with conditions that obviously meet disability standards. There is currently a large backlog of applications - some years old. Twenty-five severe rare diseases and 25 cancers have been selected thus far to profit from the accelerated processes. Many Social Security agents are unfamiliar with a majority of the 7000-plus rare diseases - a problem that slows, if not completely thwarts, the benefits approval process for these patients. The SSA programme will help rare disease patients reduce the waiting time to accessing disability assistance. Consult the list of rare conditions accorded fast-track status
First saviour sibling baby born in Spain
In October, Spain saw the birth of the nation’s first saviour sibling – a term given to babies conceived after embryonic diagnosis ensures their umbilical cord blood will be able to provide tissue-matched stem cells for an existing sibling who is sick. In the case in Spain, the baby’s six-year-old brother has beta-thalassaemia. Stem cells from the baby’s umbilical cord will be used in a bone marrow transfer in hopes of curing his sibling’s condition. Born in the region of Andalusia - the first area in Spain to allow embryo screening as a public health right - the baby was born into a maelstrom of controversy, with representatives of the Roman Catholic church expressing disapproval of the procedure. Spain legalised stem-cell research in 2006.
Yes we can! – fund embryonic stem cell research under Barack Obama’s leadership
Amongst the deluge of groups anticipating change with the remarkable momentum that swept Barack Obama to the office of 44th US president, many in the fields of rare disease scientific and medical research are hoping for a shift in policy. President Obama, a supporter of stem cell research, has not yet taken any concrete action on the subject. But these are early days. On the official website for President Obama, the Fact Sheet for science and innovation delineates the leader’s plans for the domain of science, including stem cell research:
Human embryonic stem cells have great potential for treating a wide variety of diseases and health conditions and for providing new insights into human development and disease. An Obama Administration will reverse the Bush Administration’s ban on federal funding for embryonic stem cell research on cell lines created after August 9, 2001 by executive order and will allow all scientists to participate in this important new field, in accord with the rigorous ethical guidelines proposed by the National Research Council. Consult Barack Obama and Joe Biden’s Plan for Science and Innovation

Other European news
More about the healthcare system in Turkey...
In the 21 January issue of OrphaNews Europe, pharmacist Pelin Kilic described the current situation of patient access to orphan medicinal products in Turkey. Ms. Pelin has compiled an overview of the general healthcare system in Turkey and the current healthcare policies determined by the Turkish Ministry of Health. Consult the document Turkish Healthcare Policies in Brief
Other International News
Countries gear up to celebrate the second International Rare Disease Day

28 February marks the second International Rare Disease Day. Last year, this special day was dubbed “European Rare Disease Day” but since then, the momentum has sailed around the world and three other continents have elected to get in on the action. The theme of this year’s event Patient Care: A Public Affair is especially meaningful in Europe, as the EU government moves forward the Council Recommendation on rare diseases that delineates a strategy supporting Member States in diagnosing, treating and caring for citizens with rare diseases.

International Rare Disease Day is organised by the European Organisation for Rare Diseases (EURORDIS) in conjunction with its 19 member rare disease national alliances. It is expected that the event will mobilise hundreds of patient groups and other stakeholders. A list of activities planned by countries is available on the event website and being updated regularly. Several countries have already posted events they are organising on or around 28 February, including Bulgaria, which will hold a press conference, as well as a charity art exhibit and a charity concert; Denmark, which will hold several lectures as well as other activities targeting both government and the public; Germany, whose principal patient umbrella group ACHSE is coordinating awareness raising activities in nine different cities throughout the country; Ireland, which will be hosting a meeting to consider a national rare disease plan; Italy, which will hold a seminar on rare diseases; Switzerland, which is organising a gathering for patient groups in Geneva; and the United Kingdom, which has events taking place at the UK Parliament at Westminster, as well as the Welsh Assembly and Scottish Parliament.

At the European level, a press conference at the European Commission will be hosted by European Commissioner for Health, Androulla Vassiliou. In addition, a round table dinner debate at the European Parliament will focus on the EC Communication and the Council Recommendation. The dinner will be attended by MEPs, representatives of DG SANCO, DG Research, DG Enterprise, members of the Rare Disease Task Force, and the EMEA’s Committee for Orphan Medicinal Products, patient representatives, and stakeholders from the biopharmaceutical industry.

Further abroad, in the USA rare disease day partners are writing state governors, requesting that 28 February be proclaimed Rare Disease Day in their state.

Rare Disease Day will be held on the last day of the month each February.

FDA approves world’s first embryonic stem cell-derived trial for spinal cord injury
Last month, the U.S. Food and Drug Administration approved the first-ever human trial for an embryonic stem cell-derived medical treatment. California-based Geron Corporation won approval to begin testing GRNOPC1 in patients with acute spinal cord injury. According to a news report in The Wall Street Journal, the FDA spent almost a year reviewing the 2000-plus page trial application. Geron Corp. is developing potential treatments deriving from embryonic stem cells for several conditions – including cardiac, liver, neural and bone disorders. This first trial will primarily measure safety but will also look at efficacy. The announcement of the trial approval coincides with an anticipated shift in official U.S. policy that will support embryonic stem-cell research.

New Syndromes
A recessive skeletal dysplasia resulting from a missense mutation affecting the C-type lectin domain of aggrecan
Analysis of a nuclear family with three affected offspring identified a previously unreported autosomal-recessive form of spondyloepimetaphyseal dysplasia characterised by severe short stature and a unique constellation of radiographic findings. A mutation affecting the aggrecan C-type lectin domain in regulating endochondral ossification and, thereby, height was found.
Read the PubMed abstract

Am J Hum Genet ; 72-79 ; January 2009

New Genes
Cowden and Cowden-like syndromes: germline mutations and variants in the succinate dehydrogenase genes
Cowden syndrome (CS) is an autosomal dominant disorder characterised by multiple hamartomas (occurring in the skin, breast, thyroid, gastrointestinal tract, endometrium and brain), and an increased risk of malignant tumours (breast, endometrial and thyroid cancer). Skin is involved in 90-100% of cases. Cowden syndrome results most commonly from a mutation in the PTEN gene. Many more patients with features of CS, not meeting diagnostic criteria (termed CS-like), are evaluated by clinicians for CS-related cancer risk. The authors of this study demonstrate that germline succinate dehydrogenase mutations/variants occur in a subset of PTEN mutation-negative CS/CS-like individuals and are associated with increased frequencies of breast, thyroid, and renal cancers beyond those conferred by germline PTEN mutations.
Read the PubMed abstract

To read more about "Cowden syndrome"

Am J Hum Genet ; 261-268 ; August 2008
MyD88 deficiency: pyogenic bacterial infections in patients
MyD88 is a key downstream adapter for most Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). MyD88 deficiency in mice leads to susceptibility to a broad range of pathogens in experimental settings of infection. The authors describe a distinct situation in a natural setting of human infection. Nine children with autosomal recessive MyD88 deficiency suffered from life-threatening, often recurrent pyogenic bacterial infections, including invasive pneumococcal disease. However, these patients were otherwise healthy, with normal resistance to other microbes. Their clinical status improved with age, but not due to any cellular leakiness in MyD88 deficiency. The v-dependent TLRs and IL-1Rs are therefore essential for protective immunity to a small number of pyogenic bacteria, but redundant for host defense to most natural infections.
Read the PubMed abstract

Science ; 691-696 ; 1 August 2008
Protoporphyria without anaemia or iron overload: C-terminal deletions in the ALAS2 gene cause X-linked dominant form
All reported mutations in ALAS2, which encodes the rate-regulating enzyme of erythroid heme biosynthesis, cause X-linked sideroblastic anaemia. The authors describe eight families with ALAS2 deletions resulting in frameshifts that lead to replacement or deletion of the 19-20 C-terminal residues of the enzyme. These gain-of-function mutations cause a previously unrecognised form of porphyria, X-linked dominant protoporphyria, characterised biochemically by a high proportion of zinc-protoporphyrin in erythrocytes, in which a mismatch between protoporphyrin production and the heme requirement of differentiating erythroid cells leads to overproduction of protoporphyrin in amounts sufficient to cause photosensitivity and liver disease.
Read the PubMed abstract

To read more about "Protoporphyria, erythropoietic"

Am J Hum Genet ; 408-414 ; September 2008
Nonsyndromic deafness: impairment of SLC17A8 underlies DFNA25 and inner hair cell dysfunction in null mice
Autosomal-dominant sensorineural hearing loss is genetically heterogeneous, with a phenotype closely resembling presbycusis, the most common sensory defect associated with aging in humans. The authors have identified SLC17A8, which encodes the vesicular glutamate transporter-3, as the gene responsible for DFNA25, an autosomal-dominant form of progressive, high-frequency nonsyndromic deafness.
Read the PubMed abstract

To read more about "Nonsyndromic genetic deafness"

Am J Hum Genet ; 278-292 ; August 2008
Congenital neutropenia: mutations in G6PC3
The main features of severe congenital neutropenia are the onset of severe bacterial infections early in life, a paucity of mature neutrophils, and an increased risk of leukaemia. The authors identified mutations in gene G6PC3. encoding glucose-6-phosphatase, catalytic subunit 3. Patients presented a severe congenital neutropenia syndrome associated with cardiac and urogenital malformations.
Read the PubMed abstract

To read more about "Autosomal dominant severe congenital neutropenia"

N Engl J Med ; 32-43 ; 1 January 2009
Osteopathia striata with cranial sclerosis: germline mutations in WTX at cause
Abnormalities in WNT signalling are implicated in a broad range of developmental anomalies and also in tumorigenesis. Here the authors demonstrate that germline mutations in WTX, a gene that encodes a repressor of canonical WNT signalling, cause an X-linked sclerosing bone dysplasia, osteopathia striata congenita with cranial sclerosis (OSCS). This condition is typically characterised by increased bone density and craniofacial malformations in females and lethality in males. WTX has also been shown to be somatically inactivated in 11-29% of cases of Wilms tumour. Despite being germline for such mutations, individuals with OSCS are not predisposed to tumour development.
Read the PubMed abstract

To read more about "Osteopathia striata - cranial sclerosis"

Nat Genet ; 95-100 ; January 2009
Reticular dysgenesis (aleukocytosis) is caused by mutations in the gene encoding mitochondrial adenylate kinase 2
Human severe combined immunodeficiencies (SCID) are phenotypically and genotypically heterogeneous diseases. Reticular dysgenesis is the most severe form of inborn SCID. It is characterised by absence of granulocytes and almost complete deficiency of lymphocytes in peripheral blood, hypoplasia of the thymus and secondary lymphoid organs, and lack of innate and adaptive humoral and cellular immune functions, leading to fatal septicemia within days after birth. Here two studies show that the gene encoding the mitochondrial energy metabolism enzyme adenylate kinase 2 (AK2) is mutated in individuals with reticular dysgenesis. These observations suggest that reticular dysgenesis is the first example of a human immunodeficiency syndrome that is causally linked to energy metabolism and that can therefore be classified as a mitochondriopathy.
Read the first PubMed abstract
Read the second PubMed abstract

To read more about "Reticular dysgenesis"

Nat Genet ; 101-105 ; January 2009
Nat Genet ; 106-111 ; January 2009

Congenital nail clubbing: mutation found in the HPGD gene encoding NAD+ dependent 15-hydroxyprostaglandin dehydrogenase
Isolated congenital nail clubbing (ICNC) is a rare autosomal recessive disorder characterised by enlargement of the terminal segments of fingers and toes with thickened nails due to proliferation of the connective tissues and abnormal function of the nail matrix. The authors investigated a large Pakistani family with 11 affected individuals having hereditary congenital nail clubbing as a single invariable clinical feature without any associated ectodermal, skeletal or systemic imperfection. They found a homozygous missense mutation in exon 6 of the human HPGD gene encoding NAD(+) dependent 15-hydroxyprostaglandin dehydrogenase.
Read the PubMed abstract

J Med Genet ; 14-20 ; January 2009
Radiosensitive T-B-SCID: a DNA-PKcs mutation inhibits Artemis activation and nonhomologous end-joining
Radiosensitive T-B-severe combined immunodeficiency (RS-SCID) is caused by defects in the nonhomologous end-joining DNA repair pathway, which results in failure of functional V(D)J recombination. Here the authors have identified the first human RS-SCID patient with a DNA-PKcs missense mutation (L3062R). The causative mutation did not affect the kinase activity or DNA end-binding capacity of DNA-PKcs itself; rather, the presence of long P-nucleotide stretches in the immunoglobulin coding joints indicated that it caused insufficient Artemis activation, something that is dependent on Artemis interaction with autophosphorylated DNA-PKcs.
Read the PubMed abstract

To read more about "Severe combined immunodeficiency - microcephaly - growth retardation - sensitivity to ionizing radiation"

J Clin Invest ; 91-98 ; January 2009
Recurrent pregnancy loss: mutations of the SYCP3 gene
Aneuploidy, a chromosomal numerical abnormality in the conceptus or foetus, occurs in at least 5% of all pregnancies and is the leading cause of early pregnancy loss in humans. Accumulating evidence now suggests that the correct segregation of chromosomes is affected by events occurring in prophase during meiosis I. These events include homologous chromosome pairing, sister-chromatid cohesion, and meiotic recombination. In this study, the authors show that mutations in SYCP3, a gene encoding an essential component of the synaptonemal complex that is central to the interaction of homologous chromosomes, are associated with recurrent pregnancy loss.
Read the PubMed abstract

Am J Hum Genet ; 14-20 ; January 2009
Spondylo-meta-epiphyseal dysplasia with short limbs and abnormal calcifications: mutations in DDR2 gene at cause
The spondylo-meta-epiphyseal dysplasia [SMED] short limb-hand type [SMED-SL] is a rare autosomal-recessive disease. The authors report six patients from five different consanguineous Arab Muslim families, two patients from Algerian and Pakistani ancestry and the first Jewish patients reported. They identified three missense mutations and one splice site mutation in the conserved sequence encoding the tyrosine kinase domain of the DDR2 gene.
Read the PubMed abstract

To read more about "Spondyloepimetaphyseal dysplasia - short limb - abnormal calcification"

Am J Hum Genet ; 80-84 ; January 2009
Acute necrotizing encephalopathy caused by mutations in a component of the nuclear pore RANBP2
Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). The authors identified a missense mutation in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) in a family segregating recurrent ANE as an incompletely penetrant, autosomal-dominant trait.
Read the PubMed abstract

To read more about "Necrotizing encephalopathy, acute, autosomal dominant"

Am J Hum Genet ; 44-51 ; January 2009
Amyotrophic lateral sclerosis: deleterious variants of phosphoinositide phosphatase FIG4
Mutations of the lipid phosphatase FIG4 were found in 2% (9/473) of patients with amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS). Heterozygosity for a deleterious allele of FIG4 appears to be a risk factor for ALS and PLS, extending the list of known ALS genes and increasing the clinical spectrum of FIG4-related diseases.
Read the PubMed abstract

To read more about "Primary lateral sclerosis"
To read more about "Amyotrophic lateral sclerosis"

Am J Hum Genet ; 85-88 ; January 2009

Research in Action
Fundamental Research
Myeloproliferative disorders: inhibition of the Bcl-xL deamidation pathway
The molecular mechanisms in myeloproliferative disorders that prevent apoptosis induced by damaged DNA are obscure. The authors searched for abnormalities of the proapoptotic Bcl-x(L) deamidation pathway in primary cells from patients with chronic myeloid leukemia (CML) or polycythemia vera, myeloproliferative disorders associated with the BCR-ABL fusion kinase and the Janus tyrosine kinase 2 (JAK2) V617F mutation, respectively. The Bcl-x(L) deamidation pathway was inhibited in myeloid cells, but not T cells, in patients with CML or polycythemia vera. BCR-ABL and mutant JAK2 inhibit the Bcl-x(L) deamidation pathway and the apoptotic response to DNA damage in primary cells from patients with CML or polycythemia vera.
Read the PubMed abstract

To read more about "Chronic myeloid leukemia"

N Engl J Med ; 2778-2789 ; 25 December 2008
Clinical Research
Congenital erythrocytosis: PHD2 mutation linked to paraganglioma in patients
The authors describe a patient with erythrocytosis (also known as polycythemia) and recurrent paraganglioma carrying a newly discovered PHD2 mutation. This mutation affects PHD2 function and stabilizes HIF-alpha proteins. In addition, the authors demonstrate loss of heterozygosity of PHD2 in the tumour, suggesting that PHD2 could be a tumour-suppressor gene.
Read the PubMed abstract
To read more about "
Primary familial polycythemia"

N Engl J Med ; 2685-2692 ; 18 December 2008
Glioblastoma: two new studies find several genes implicated
Glioblastoma multiforme (GBM) is the most common and lethal type of brain cancer. Two new studies find several new genes implicated in the disease. To identify the genetic alterations in GBMs, the authors of the first study sequenced 20,661 protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleotide arrays, and performed gene expression analyses using next-generation sequencing technologies in 22 human tumour samples. This comprehensive analysis led to the discovery of a variety of genes that were not known to be altered in GBMs, most notably, recurrent mutations in the active site of isocitrate dehydrogenase 1 (IDH1) in 12% of GBM patients. Mutations in IDH1 occurred in a large fraction of young patients and in most patients with secondary GBMs and were associated with an increase in overall survival. The second study, conducted by the Cancer Genome Atlas, analysed 206 glioblastomas, finding new insights into the roles of ERBB2, NF1 and TP53, and uncovering frequent mutations of the phosphatidylinositol-3-OH kinase regulatory subunit gene PIK3R1. This large-scale study also provides a network view of the pathways altered in the development of glioblastoma.
Read the first PubMed abstract
Read the second PubMed abstract

To read more about "Glioblastoma"

Nature ; 1061-1068 ; 23 October 2008
Science ; 1807-1812 ; 26 September 2008

Retinoblastoma: a review of findings from 2007-2008
This review highlights many of the most important articles published from June 2007 to May 2008 on retinoblastoma. Significant advances in molecular biology, translational research, and clinical reports are detailed. The most significant recent findings include the evidence for aneuploidy and genomic instability as cancer causes rather than the long-held Knudson’s ‘two-hit’ hypothesis; the evidence that retinoma may represent a precursor lesion for retinoblastoma prior to the acquisition of genomic instability; and the evidence that a horizontal interneuron may be the cell of origin in murine knockout retinoblastoma and may be capable of clonal expansion after differentiation. Translational studies also demonstrate promise for the use of topotecan and 2-deoxy-D-glucose in children. The introduction of intraarterial chemotherapy for human intraocular retinoblastoma appears to be safe and effective and may eliminate the need for enucleation in many patients.
Read the PubMed abstract

To read more about "Retinoblastoma"

Curr Opin Ophthalmol ; 526-534 ; November 2008
Acquired lipodystrophy associated with activation of the classical complement pathway
The authors describe an immunologically distinct form of acquired generalised lipodystrophy, with evidence of activation of the classical complement pathway (low C4) and autoimmune hepatitis in three patients manifesting near-total lipodystrophy, chronic hepatitis with autoimmune features, and low C4 complement levels.
Read the PubMed abstract

J Clin Endocrinol Metab ; 10-16 ; January 2009

Patient Management and Therapy
Wegener granulomatosis and microscopic polyangiitis: azathioprine or methotrexate are similar for maintenance therapy
Current standard therapy for Wegener granulomatosis and microscopic polyangiitis combines corticosteroids and cyclophosphamide to induce remission, followed by a less toxic immunosuppressant such as azathioprine or methotrexate for maintenance therapy. However, azathioprine and methotrexate have not been compared with regard to safety and efficacy. In this prospective, open-label, multicenter trial, the authors randomly assigned patients with Wegener granulomatosis or microscopic polyangiitis who entered remission with intravenous cyclophosphamide and corticosteroids to receive oral azathioprine or methotrexate for 12 months. The study found that the two agents appear to be similar alternatives for maintenance therapy in patients with Wegener granulomatosis and microscopic polyangiitis after initial remission.
Read the PubMed abstract

To read more about "Wegener granulomatosis"
To read more about "Microscopic polyangiitis"

N Engl J Med ; 2790-2803 ; 25 December 2008
Mucopolysaccharidosis I: long-term efficacy and safety of laronidase
The authors evaluated the long-term safety and efficacy of recombinant human alpha-l-iduronidase (laronidase) in 40 patients with mucopolysaccharidosis I. Patients demonstrated gradual and sustained clinically meaningful improvement in activities of daily living over the treatment period. Laronidase infusions were generally well tolerated. Antibodies to laronidase developed in 93% of the patients.
Read the PubMed abstract

To read more about "Mucopolysaccharidosis type 1"

Pediatrics ; 229-240 ; January 2009
Marfan syndrome and related type I fibrillinopathies: diagnostic criteria not applicable in childhood
From a large series of 1009 probands with pathogenic FBN1 mutations, data for 320 patients <18 years of age at the last follow-up evaluation were analyzed. At the time of diagnosis, the median age was 6.5 years. Only 56% of children could be classified as having Marfan syndrome, according to international criteria, at their last follow-up evaluation when the presence of a FBN1 mutation was not considered as a major feature, with increasing frequency in the older age groups. Eighty-five percent of child probands fulfilled international criteria after molecular studies, which indicates that the discovery of a FBN1 mutation can be a valuable diagnostic aid in uncertain cases. Apart from lethal neonatal Marfan syndrome, this study confirms that the majority of clinical manifestations of Marfan syndrome increase with age, emphasising the poor applicability of the international criteria to this diagnosis in childhood and the need for follow-up monitoring in cases of clinical suspicion of Marfan syndrome.
Read the PubMed abstract

To read more about "Marfan syndrome"

Pediatrics ; 391-398 ; January 2009
Mucopolysaccharidosis I: management and treatment guidelines
Twelve international experts on mucopolysaccharidosis I met to draft management and treatment guidelines for mucopolysaccharidosis I. Recommendations are based on extensive clinical experience and a review of the literature. All patients with mucopolysaccharidosis I should receive a comprehensive baseline evaluation, including neurologic, ophthalmologic, auditory, cardiac, respiratory, gastrointestinal, and musculoskeletal assessments, and should be monitored every 6 to 12 months with individualised specialty assessments, to monitor disease progression and effects of intervention. Patients are best treated by a multidisciplinary team. Treatments consist of palliative/supportive care, hematopoietic stem cell transplantation, and enzyme replacement therapy. A standard of care for the treatment of patients with mucopolysaccharidosis I will optimise clinical outcomes and patient quality of life.
Read the PubMed abstract

To read more about "Mucopolysaccharidosis type 1"

Pediatrics ; 19-29 ; January 2009
Models of comprehensive multidisciplinary care for individuals with genetic disorders
This USA-based study finds that there is uneven availability and utilisation of multidisciplinary specialty clinics for different genetic diseases. For two disorders (ie, hemophilia and cystic fibrosis), effective national networks of specialty clinics exist and reach large proportions of the target populations. For other disorders, notably, sickle cell disease, fewer such centres are available, centres are less likely to be networked, and are used less widely. Models of co-management are essential for promoting ongoing communication and coordination between primary care and subspecialty services, particularly during the transition from paediatric care to adult care. Evaluation of the effectiveness of different models in improving outcomes for individuals with genetic diseases is essential.
Read the PubMed abstract

Pediatrics ; 407-412 ; January 2009

Orphan Drugs
FDA licenses orphan drug to treat bleeding in congenital fibrinogen deficiency
The U.S. Food and Drug Administration has approved licensing for RiaSTAP, for the treatment of bleeding in patients with congenital fibrinogen deficiency. RiaSTAP [Fibrinogen Concentrate (Human)] is an orphan drug developed under the FDA’s accelerated approval regulations. The drug is manufactured by CSL Behring (Germany).
FDA Approves Mozobil to increase blood stem cells for bone marrow transplants
The U.S. Food and Drug Administration has approved Mozobil (plerixafor) to help increase the number of blood stem cells for bone marrow transplantation in patients with certain forms of blood cancer. Mozobil is an injectable drug intended to be used in combination with the growth factor granulocyte-colony stimulating factor (G-CSF), for treatment of adults with multiple myeloma or non-Hodgkin lymphomas. Mozobil is manufactured by Genzyme Corp., Cambridge, Mass.

News from the Patients' Associations
A video contest for International Rare Disease Day
On the occasion of the second International Rare Disease Day, taking place on 28 February 2009, the European Organisation for Rare Diseases (EURORDIS) is holding a video competition. Anyone can submit a video on the topic of living with a rare disease. This could include rare disease patients in every day life, in the medical environment, or at school or work. Participants are invited to upload original video entries no more than 10 minutes in length. For more details

Courses & Educational Initiatives
EuroGentest Quality Management and Accreditation/Certification of Genetic Testing Training Workshops - 2009
EuroGentest, an EU-funded Network of Excellence working to improve and harmonise all aspects of genetic testing, is offering a series of workshops throughout the year in the area of Quality Management and Accreditation/Certification of Genetic Testing:

Towards accreditation - Managing the human side of change
Venue: Leuven, Belgium
Date: 20-21 April 2009
For further details

Accreditation for beginners
Venue: Vienna, Austria
Date: 22-23 May 2009
For further details

Fulfilling the requirements of ISO 15189 for management review, IQC and EQA
Venue: Vienna, Austria
Date: 22-23 May 2009
For further details

Case studies on quality assurance and quality control issues in genetic testing laboratories at the ESHG
Venue: Vienna, Austria
Date: 24 May 2009 (10.15 am - 11.15 am)
For further details

Quality and Laboratory Management - A EuroGentest symposium for human genetic testing laboratories
Venue: Leuven, Belgium
Date: 18-19 June 2009
For further details

Basic workshop on validation of diagnostic tests in clinical molecular genetics
Venue: Bologna, Italy
Date: 26-27 October 2009
For further details


What's on Where?
Orphan Drugs and Rare Diseases IV International Congress
Date: 19-21 February 2009
Venue: Seville, Spain

Organised by the Pharmacist Official College of Seville and the Rare Diseases Spanish Federation, the theme of this congress is "Rare Diseases and Their Treatment: A Decade of Advances".
For further details

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

More detailed information will follow soon.
For further details

IPPOSI: Focus on Rare Diseases in Ireland - What is the National Plan?
Date: 25 February 2009
Venue: Dublin, Ireland

The Irish Platform for Patients’ Organisations, Science and Industry (IPPOSI), the Genetic and Rare Disorders Organisation (GRDO) and the Medical Research Charities Group (MRCG) are holding a meeting bringing together speakers from all sectors in Ireland and Europe to look at diagnosis, treatment and access to medicines for people with a rare disease in Ireland and to consider a national plan of action.
For further details

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

Check with the official website in coming weeks to locate activities in your region.
For further details

Innovative Approaches for Innovative Therapies
Date: 2-3 March 2009
Venue: Edmonton, Canada

The workshop brings together patients, policy makers and manufacturers to consider strategies for providing access to innovative therapies to patients with rare and other conditions.
For further details

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

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

European Parliament Workshop on Direct to Consumer Genetic Testing
Date: 3 March 2009
Venue: Brussels, Belgium

A European Parliament Science and Technology Options Assessment project provides an overview of the current discussion on Direct to Consumer Genetic Testing among experts and public authorities and on the current status of offers on the internet. Possible options and needs for political intervention such as an amendment of the European Directive for In-Vitro-Diagnostic Devices are also discussed. At this workshop central results of the project will be presented and discussed with a group of experts.

For further details

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

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

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

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

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. 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. Deadline to submit an abstract is 20 January 2009.
For further details

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

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

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

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

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

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

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

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

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 (USA)

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


Press & Publications
Australian study of rare childhood disorders confirms that national approach presents best route to addressing needs
A recent review article written by Australian experts querys: Rare childhood diseases: how should we respond? The authors take the examples of Rett syndrome and foetal alcohol syndrome and apply three pertinent questions:
  • What are the impacts of rare diseases on patients, families, caregivers and the community?
  • What are the impacts of rare diseases on clinicians and health services?
  • How have governments responded to the need for health services, research and policies relating to rare diseases?
  • Their research reveals the psychological and economic stress experienced by patients and their families, along with the social impact of isolation, stigmatisation, discrimination, and reduced educational/employment opportunities often described. Moreover, caring for a child with a rare, debilitating condition is expensive.

    Clinicians and health services face their own set of challenges: standardised diagnostics are frequently nonexistent, as are treatments, management guidelines, and referral pathways. The third question of the review article outlines the different responses from governments around the world. The authors acknowledge that developing a national approach similar to those used in Europe (particularly France) and the USA could “provide important roadmaps to address common issues faced by people with rare diseases”. Australia defines a rare disease as a disorder with a prevalence of 1/10 000 (versus 1/2000 in Europe), affecting some 1.2 million Australians. The study concludes with a call for “priority funding for research into the health, social and economic burdens of rare diseases and the needs of affected individuals…required to provide an evidence base to support public health policy”.
    Consult the PubMed abstract


    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, Benjamin Guesdon, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Charlotte Rodwell, Paloma Tejada, Aurélie Vandeputte
    National Contact Point: Till Voigtländer (Austria), 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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