28 October 2009 print
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Olé! Spain officially launches national rare disease strategy and inaugurates specialised centre for social needs
The official launch of Spain’s rare disease strategy took place on 20 October. As was reported in the 10 July 2009 issue of OrphaNews Europe, the Spanish Ministry of Health this summer announced the establishment of a national strategy for its estimated 3 million rare disease patients and their families. The Spanish plan is essentially a coordination tool based upon seven strategic lines that will encompass the domains of information; prevention and early detection; healthcare coordination; treatment (including advanced medicinal products, orphan drugs, and related materials); social services; research; and training. The elements defined in the Spanish strategy follow the recommendations delineated by the European Council Recommendation on an Action in the Field of Rare Diseases. The Spanish strategy is available for consultation online in Spanish language.

Under the Social Services element of the strategy, a national centre for rare disease patients has been established and was officially inaugurated by Spanish Minister of Health and Social Policy, Trinidad Jimenez on 30 September in Burgos, Spain. The residential and outpatient centre offers specialised social support services for patients and their caregivers, particularly facilitating personal autonomy and social participation for rare disease patients.


Spotlight on...
The Philippine Society for Orphan Disorders campaigns for rare disease resources via a Senate bill

Even for the world’s most financially robust countries, finding room in their budgets for rare disease research, care and treatment is problematic. For developing countries, the challenge is Herculean. The non-profit Philippine Society for Orphan Disorders (PSOD) was created in June 2006 in order to lend support and sustainability to the small number of medical professionals working with rare disease patients in the Republic of the Philippines, a country of 7,107 islands with a total population of 92 million people. The PSOD is seeking to position itself as the country’s “central network for the advocacy and effective coordination of all viable efforts to sustain a better quality of life for the individuals with orphan or rare disorders in the Philippines”. The group’s mission is to “uphold the primary concerns and welfare of individuals with rare disorders by directly addressing, supporting and protecting their health and general well being”. The PSOD is chaired by Dr. Carmencita D. Padilla, Professor of Paediatrics at the College of Medicine, University of the Philippines Manila and Director of the Institute of Human Genetics, National Institutes of Health Philippines. Dr. Padilla also heads the Newborn Screening Reference Center, and co-chairs the National Technical Working Group on Newborn Screening at the Department of Health. Other PSOD board members consist of both professionals and parents of patients, including the organisation’s president, business woman Cynthia K. Magdaraog, the parent of a patient with Pompe disease. Amongst the goals the organisation has identified is increasing public awareness; developing and establishing a nationwide registry of relevant and material statistical information, (including medications, drug trials and other pertinent information about orphan disorders); assisting patients, their families, family support groups, doctors and researchers in the management of these conditions; promoting and supporting relevant and timely research; participating in policy formulation, advocacy and legislation of national and international relevance; developing and strengthening the relationship among institutions that are involved in the care of individuals with orphan disorders; developing and providing training for parents, families, health professionals, paramedical personnel and community health workers on the care of patients with orphan disorders; developing PSOD members’ core competencies in the management of orphan disorders; and being financially self-reliant, mobilising resources in the pursuit of organisational objectives.

In the Philippines, a rare disease is defined as a condition or illness affecting “no more than one in 20,000 individuals in the country”. The PSOD has several initiatives in place to help rare disease patients and their families, including the Endowment Fund and The Emergency Fund. The Endowment Fund is designed to help sustain long-term treatments that many diseases require. This fund also assists research for rare disorders and aims to make the PSOD self sustaining. The Emergency Fund is for the immediate needs of patients undergoing medical emergencies and can be used for life saving medicines, hospitalisation, the purchase of supportive medical devices, and other uses. The PSOD uses annual reports and other publications to communicate how donor funds are used.

The Rare Diseases Act of the Philippines
To work toward these objectives, the group has campaigned actively to put forward a bill that would make providing resources for rare disease patients a part of the country’s legal responsibilities. Currently pending, Senate Bill No. 3087: the Rare Diseases Act of the Philippines is sponsored by Senator Edgardo Angara, a fervent supporter of the scientific community. Bill 3087 seeks to ensure that every patient diagnosed with a rare disorder “has access to timely health information and adequate medical care, including drugs and other healthcare products to treat or otherwise help them cope with their condition.” Amongst the bill’s components is the call for the creation of an Office of Rare Diseases within the country’s department of health that would oversee research, create and maintain a registry, and conduct public awareness programmes. The bill also calls for “regulatory and fiscal incentives to support research and development activities on rare diseases and the import or manufacture of affordable orphan drugs or orphan products; and institutionalise a financial incentive system for agencies involved in clinical research, patient care, medical information management, and other similar activities for the benefit of persons afflicted with a rare disease”. The PSOD is sponsoring a petition to get the Rare Diseases Act passed and has set a goal of 500,000 signatures. Consult Bill 3087
Sign the Petition supporting Bill 3087

Project Rare and Care for Rare
The PSOD’s Project Rare initiative launched in February of this year. Designed to heighten public awareness, a series of activities specifically seek to identify and add patients to the rare disease registry; build patient and caregiver networks; and create an endowment fund.

Another PSOD project that got off the ground this year is the group’s first newsletter. Care for Rare reports on the activities taking place in the rare disease community, helping to foster collaboration and communication. The newly-revamped PSOD website also publicises news from the rare disease community, including Patient Welfare Activities project reports, which list donations received and how the funds were specifically applied within the rare disease community. The group further enhances its visibility by taking advantage of free networking resources such as Facebook, You Tube and Twitter.

Genzyme is a partner of the PSOD and also provides free treatments to certain Filipino patients with rare disorders Gaucher disease and Pompe disease under its International Compassionate Access Programme. The PSOD was present at the recent International Conference of National Policies and actions on Rare Diseases that took place in Taiwan and engages with several countries in the region as well as with stakeholders in the USA and Europe. OrphaNews Europe will be keeping a close watch on the PSOD and on Senate Bill 3087 in order to report any breaking developments in the struggle to secure aid for rare disease patients and their families in the Philippines.


National & International Policy Developments
Pending US act calls for rare disease expert panel for comparative clinical effectiveness research
In June, the Patient-Centered Outcomes Research Act of 2009 (S.1213) was introduced in the US Senate to amend title XI of the Social Security Act to provide for a programme of comparative effectiveness research for health care. This measure would establish a non-profit corporation (the Patient-Centered Outcomes Research Institute) to “provide for the generation and synthesis of comparative clinical evidence of which health care interventions and services work and which ones don’t” by comparing clinical outcomes and clinical effectiveness of alternative therapies and health strategies for the same condition. Importantly for the rare disease community, this act contains a provision that would require consultation with an expert advisory panel each time a clinical effectiveness study is conducted for a rare disease. Such a mechanism is considered “a critical safeguard” for patients with rare conditions. The panel would consist of practicing and research clinicians (including relevant specialists and subspecialists); experts in scientific and health services research, health services delivery, and evidence-based medicine; a representative of each manufacturer of all medical technologies included under the relevant topic; and supporting patient and consumer representatives. The bill has been referred to the Senate Finance Committee for review. Consult Bill S.1213
Other European news
UK’s Diagnostic Mutation Database extends access to geneticists worldwide

The United Kingdom’s Diagnostic Mutation Database (DMuDB), a central repository for sharing gene variant data between UK diagnostic genetics laboratories, was established by the National Genetics Reference Laboratory (NGRL) Manchester in 2002. DMuDB allows UK scientists working within the National Health Service to determine the significance of variants not previously identified by their own laboratory. Now, the DMuDB is launching a new enquiry service that extends the knowledge of DMuDB to geneticists throughout the world. The DMuDB has established a secure web page through which international geneticists with “a legitimate interest” are able to request information on a particular variant. Should the requested variant be present in DMuDB, inquirers will receive contact details for the relevant National Health Service laboratory so that they can establish contact. Nearly 6,000 records for 83 genes are currently recorded in DMuDB, containing over 12,000 individual variants. Well represented genes include MLH1, MSH2, MSH6, APC, CFTR, MEN1, NF1, NF2, RPGR and TSC2. For further information

The Netherlands again sweeps the European Health Consumer Index
Sweden-based Health Consumer Powerhouse, a leading provider of consumer health information in Europe, has released its 2009 Euro Health Consumer Index (EHCI), an annual user-focused report that assesses 33 healthcare systems across Europe. The Netherlands has once again come out on top – its strong health system qualified as not having “any weak spots” aside from waiting times. The Netherlands has ranked in the top three since the survey began in 2005. Interestingly, the report notes that the Netherlands “probably has the best and most structured arrangement for patient organisation participation in healthcare decision and policymaking in Europe”. To measure the performance of each country, the EHCI identified 38 health performance indicators organised into six general categories (patient rights and information, e-Health, waiting time for treatment, outcomes, range and reach of services provided, and pharmaceuticals). Denmark again took second place, followed by newcomer Iceland in third place and Austria in fourth. The 2009 report warns that “expanding inequalities in healthcare following on the financial crisis challenge EU principles of solidarity and equity…. With patient mobility growing around Europe, there is a strong need for transparency exposing the pros and cons of the national healthcare systems.” Issues of patient mobility and participation are particularly critical to rare disease care and treatment. Consult the report
Other International News
The FaceBase project will compile a database of craniofacial development, genetics, and diseases
In the USA, the NIH’s National Institute of Dental and Craniofacial Research has awarded 11 research and technology grants under its newly-formed FaceBase project that seeks to forward understanding of craniofacial development and disorders. A FaceBase Consortium will consist of “collaborative research projects, each comprising a multidisciplinary team sharing a common research focus, and targeting their studies at specific aspects of craniofacial development (e.g., cranial neural crest migration, formation of lip and palate, cranial sutures, tooth, salivary gland or temporomandibular joint) and associated clinical conditions”. The five-year initiative will “systematically compile the biological instructions to construct the middle region of the human face and precisely define the genetics underlying its common developmental disorders, such as cleft lip and palate”. A “one-stop, encyclopedic database of …craniofacial development will be created and maintained to allow scientists to mine the riches of the information enabling them to more rapidly and effectively generate hypotheses and accelerate the pace of their research”. While some 70% of cleft lip or palate cases present as an isolated condition, over 300 syndromes have been identified that include cleft lip or palate as part of their clinical spectrum and many other types of craniofacial anomalies are present in rare disorders. Learn more about the FaceBase Consortium and its grant recipients

EU Project Follow-up
ECORN-CF expertise being exploited more often, in more countries

The 17 September 2008 issue of OrphaNews Europe featured an article on innovative project ECORN-CF, the European Centres of Reference Network for Cystic Fibrosis that was selected for funding under the EU 2003-2008 public health action programme that prioritises the development of European Networks of Reference Centres for Rare Diseases. ECORN-CF offers a unique quality-controlled shared-knowledge database that responds to both patient and professional queries concerning cystic fibrosis. An article in the latest ECORN-CF newsletter provides robust evidence that the network’s system of sharing and communicating knowledge and expertise for cystic fibrosis is being used more often and in more countries. Indeed, between April and August 2009, the number of queries archived by the network increased over 25%. Queries are being received from twice as many countries since the network debuted. Not all queries and responses are stored in the website’s central archives. Local questions (typically involving issues of reimbursement, for example) would be logged locally.


Orphanet News
New Texts
New Orphanet Journal of Rare Diseases publications

Familial adenomatous polyposis
Fabry disease: recent advances in pathology, diagnosis, treatment and monitoring


New Syndromes
A new microduplication syndrome encompassing the region of Miller-Dieker syndrome
This report describes three children with de novo 17p13.1 duplications encompassing the PAFAH1B1 gene, who had similar phenotypic features, including mild to moderate developmental delay, hypotonia and facial dysmorphism, and compares them to the few previously reported cases with this duplication. In contrast to patients with deletion of the region (Miller-Dieker syndrome) the patients reported here had mild to moderate delay and displayed no lissencephaly or gross brain malformations.
Read the PubMed abstract

J Med Genet ; 703-710 ; October 2009
Combined immunodeficiency associated with DOCK8 mutations
Recurrent sinopulmonary and cutaneous viral infections with elevated serum levels of IgE are features of some variants of combined immunodeficiency. The genetic causes of these variants are unknown. The authors collected longitudinal clinical data on 11 patients from eight families who had recurrent sinopulmonary and cutaneous viral infections. Patients had recurrent otitis media, sinusitis, and pneumonias; recurrent staphylococcus aureus skin infections with otitis externa; recurrent, severe herpes simplex virus or herpes zoster infections; extensive and persistent infections with molluscum contagiosum; and human papillomavirus infections. Most patients had severe atopy with anaphylaxis; several had squamous-cell carcinomas, and one had T-cell lymphoma-leukaemia. Novel homozygous or compound heterozygous deletions and point mutations in the gene encoding the dedicator of cytokinesis 8 protein (DOCK8) led to the absence of DOCK8 protein in lymphocytes.
Read the PubMed abstract

N Engl J Med ; Epub ahead of print ; 23 September 2009

New Genes

Nephronophthisis with liver fibrosis: hypomorphic mutations in meckelin (MKS3/TMEM67) at cause
Nephronophthisis (NPHP), also known as Boichis syndrome, a rare recessive cystic kidney disease, is the most frequent genetic cause of chronic renal failure in children and young adults. Mutations in nine genes (NPHP1-9) have been identified. NPHP can be associated with retinal degeneration (Senior-Løken syndrome), brainstem and cerebellar anomalies (Joubert syndrome), or liver fibrosis. To identify a causative gene for the subset of patients with associated liver fibrosis, the authors performed a genome wide linkage search in a consanguineous family with three affected patients. They found hypomorphic MKS3/TMEM67 mutations. This is the first report of MKS3 mutations in patients with no vermian agenesis and without neurological signs.
Read the PubMed abstract

To read more about "Boichis disease"

J Med Genet ; 663-670 ; October 2009
Autosomal-recessive nonsyndromic hearing loss: mutations in LOXHD1 disrupt hair cell function
Hearing loss is the most common form of sensory impairment in humans and is frequently progressive in nature. Here the authors identified a mutation in LOXHD1, which causes DFNB77, a progressive form of autosomal-recessive nonsyndromic hearing loss (ARNSHL). LOXHD1, MYO3a, and PJVK are the only human genes to date linked to progressive ARNSHL. These three genes are required for hair cell function, suggesting that age-dependent hair cell failure is a common mechanism for progressive ARNSHL.
Read the PubMed abstract

To read more about "Nonsyndromic genetic deafness"

Am J Hum Genet ; 328-337 ; September 2009
Emery-Dreifuss muscular dystrophy: mutations of the FHL1 gene at cause
Emery-Dreifuss muscular dystrophy (EDMD) is a rare disorder characterised by early joint contractures, muscular dystrophy, and cardiac involvement with conduction defects and arrhythmias. So far, only 35% of EDMD cases are genetically elucidated and associated with EMD or LMNA gene mutations, suggesting the existence of additional major genes. The authors identified FHL1 gene mutations in three informative families belonging to a EMD- and LMNA-negative cohort.
Read the PubMed abstract

To read more about "Emery-Dreifuss muscular dystrophy"

Am J Hum Genet ; 338-353 ; September 2009
LEOPARD syndrome: novel BRAF mutation in a patient with normal intelligence
Noonan syndrome (NS) and related disorders are caused by mutations in various genes encoding molecules involved in the RAS-MAPK signalling cascade. There are strong genotype-phenotype correlations. BRAF is the major gene for cardio-facio-cutaneous syndrome (CFCS), and usually patients with a BRAF mutation have significant cognitive impairment. The authors report on a patient with LEOPARD syndrome and normal intelligence who was found to carry a novel sequence change in BRAF. This observation illustrates that the phenotypic spectrum caused by BRAF mutations is broader than previously assumed and that intellectual deficit is not necessarily associated.
Read the PubMed abstract

To read more about "LEOPARD syndrome"

Eur J Med Genet ; 337-340 ; September-October 2009
Bleeding diathesis due to glycoprotein VI deficiency: composite GPVI mutations identified
The glycoprotein VI (GPVI)/FcRgamma complex is a key receptor for platelet activation by collagen. The authors describe, for the first time, two genetic abnormalities in one patient. A 10-year-old girl presented ecchymoses since infancy, a prolonged bleeding time despite a normal platelet count and no antiplatelet antibodies. Collagen-induced platelet activation was null, whereas GPVI quantification by flow cytometry evidenced an incomplete deficiency. Immunoblotting showed an abnormal migration of residual GPVI, and no FcRgamma defect. GPVI DNA sequencing revealed (1) an R38C mutation in exon 3 of one allele and (2) an insertion of 5 nucleotides in exon 4 of the other allele, leading to a premature nonsense codon and absence of the corresponding mRNA. Introduction of the R38C mutation into recombinant GPVI-Fc resulted in abnormal protein migration and a loss of collagen binding. Thus, this composite genetic GPVI deficiency and dysfunction cause absence of platelet responses to collagen and a mild bleeding phenotype.
Read the PubMed abstract

To read more about "Bleeding diathesis due to glycoprotein VI deficiency or integrin alpha2-beta1 deficiency"

Blood ; 1900-1903 ; 27 August 2009

Research in Action

Fundamental Research
Maternally inherited genetic diseases: mitochondrial gene replacement could prevent transmission
Unlike the nuclear genome, which is derived from both the egg and sperm at fertilization, the mtDNA in the embryo is derived almost exclusively from the egg; that is, it is of maternal origin. Mutations in mtDNA contribute to a diverse range of currently incurable rare human diseases and disorders. The authors demonstrate that the mitochondrial genome can be efficiently replaced in mature non-human primate oocytes by spindle-chromosomal complex transfer from one egg to an enucleated, mitochondrial-replete egg. The reconstructed oocytes with the mitochondrial replacement were capable of supporting normal fertilisation, embryo development and produced healthy offspring. Genetic analysis confirmed that nuclear DNA in the three infants born so far originated from the spindle donors whereas mtDNA came from the cytoplast donors. No contribution of spindle donor mtDNA was detected in offspring. This approach may thus offer a reproductive option to prevent mtDNA disease transmission in affected families.
Read the PubMed abstract

Nature ; 367-372 ; 17 September 2009
Clinical Research
Li-Fraumeni: high frequency of de novo mutations
Li-Fraumeni syndrome is an autosomal dominant cancer predisposition syndrome caused by germline mutations in the TP53 gene. The authors report that germline de novo TP53 mutations are relatively common. This has implications for testing and the identification of potential Li-Fraumeni syndrome in patients with little or no family history of cancer.
Read the PubMed abstract

To read more about "Li-Fraumeni syndrome"

J Med Genet ; 689-693 ; October 2009
Fragile X syndrome: penetrance of FMR1 premutation-associated pathologies in families
Within the past few years, there has been a significant change in identifying and characterising the FMR1 premutation-associated phenotypes. It has been established that approximately 20% of female premutation carriers present primary ovarian insufficiency (POI) and that fragile X-associated tremor/ataxia syndrome (FXTAS) occurs in one-third of all male premutation carriers older than 50 years. Besides POI and FXTAS, new disorders have recently been described among individuals (especially females) with the FMR1 premutation, including thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia. However there are few reports related to FXTAS penetrance among female premutation carriers or regarding these disorders recently associated to the FMR1 premutation. The authors here show that signs of FXTAS are detected in 16.5% of female premutation carriers and in 45.5% of premutated males older than 50 years. Furthermore, among females with the FMR1 premutation, penetrance of POI, thyroid disease and chronic muscle pain is 18.6, 15.9 and 24.4%, respectively.
Read the PubMed abstract

To read more about "Fragile X syndrome"

Eur J Hum Genet ; 1359-1362 ; October 2009
Goltz-Gorlin syndrome: no phenotype and genotype correlation in 17 patients
Goltz-Gorlin syndrome or focal dermal hypoplasia is a highly variable, X-linked dominant syndrome with abnormalities of ectodermal and mesodermal origin. In 2007, mutations in the PORCN gene were found to be causative. Here, a series of 17 patients with Goltz-Gorlin syndrome is reported on, and their phenotype and genotype are described. PORCN mutations can be found in all classically affected cases of Goltz-Gorlin syndrome, including males. Somatic and germline mosaicism occur. There is no evident genotype-phenotype correlation.
Read the PubMed abstract

To read more about "Focal dermal hypoplasia"

J Med Genet ; 716-720 ; October 2009
Noonan syndrome: multiple giant cell lesions are a complication of the dysregulated RAS/MAPK signalling pathway
The authors report five cases of multiple giant cell lesions in patients with typical Noonan syndrome. Such association has frequently been referred to as Noonan-like/multiple giant cell (NL/MGCL) syndrome before the molecular definition of Noonan syndrome. Two patients show mutations in PTPN11 and three in SOS1. MGCL lesions were observed in jaws (cherubism) and joints (pigmented villonodular synovitis). The authors show through those patients that both types of MGCL are not PTPN11-specific, but rather represent a low penetrant (or perhaps overlooked) complication of the dysregulated RAS/MAPK signalling pathway. They recommend discarding NL/MGCL syndrome from the nosology, as this presentation is neither gene-nor allele-specific of Noonan syndrome; these patients should be described as Noonan syndrome with MGCL (of the mandible, the long bone...). The term cherubism should be used only when multiple giant cell lesions occur without any other clinical and molecular evidence of Noonan syndrome, with or without mutations of the SH3BP2 gene.
Read the PubMed abstract

To read more about "Noonan syndrome"

Eur J Hum Genet ; 1216-1221 ; October 2009
Idiopathic dilated cardiomyopathy: the role of sarcomere gene mutations
The authors investigated a Danish cohort of 31 unrelated patients with idiopathic dilated cardiomyopathy (IDC), to assess the role that mutations in sarcomere protein genes play in IDC. Disease-causing sarcomere gene mutations were found in about one-quarter of IDC patients, and seem to play an important role in the causation of the disease. These data suggest that a genetic work-up should include screening of the most prominent sarcomere genes even in the absence of a family history of the disease.
Read the PubMed abstract

Eur J Hum Genet ; 1241-1249 ; October 2009
Spinal muscular atrophy: a positive modifier of in the SMN2 gene
Spinal muscular atrophy (SMA) is a common autosomal-recessive motor neuron disease caused by the homozygous loss of the SMN1 gene. A nearly identical gene, SMN2, has been shown to decrease the severity of SMA in a dose-dependent manner. However SMN2 is not the sole phenotypic modifier, because there are discrepant SMA cases in which the SMN2 copy number does not explain the clinical phenotype. This report describes three unrelated SMA patients who possessed SMN2 copy numbers that did not correlate with the observed mild clinical phenotypes. A single base substitution in SMN2, c.859G>C, was identified in exon 7 in the patient DNA. The authors show that the change creates a new exonic splicing enhancer element and increases the amount of full-length transcripts, thus resulting in the less severe phenotypes. This demonstrates that the c.859G>C substitution is a positive modifier of the SMA phenotype and that not all SMN2 genes are equivalent.
Read the PubMed abstract

To read more about "Proximal spinal muscular atrophy"

Am J Hum Genet ; 408-413 ; September 2009
Huntington disease: cross-sectional analysis of baseline data
Huntington disease (HD) is an autosomal dominant, fully penetrant, neurodegenerative disease that most commonly affects adults in mid-life. The authors show the feasibility of rapid data acquisition and the use of multi-site 3T MRI and neurophysiological motor measures in a large multicentre study. Their results provide evidence for quantifiable biological and clinical alterations in HTT expansion carriers compared with age-matched controls. These findings might help to define novel quantifiable endpoints and methods for rapid and reliable data acquisition, which could aid the design of therapeutic trials.
Read the PubMed abstract

To read more about "Huntington disease"

Lancet Neurol ; 791-801 ; September 2009

Patient Management and Therapy

Paragangliomas: succinate dehydrogenase genetic testing in a large prospective series of patients
Germline mutations in SDHx genes cause hereditary paraganglioma. To assess the indications for succinate dehydrogenase (SDH) genetic testing in a prospective study, a total of 445 patients with head and neck and/or thoracic-abdominal or pelvic paragangliomas were recruited. Results showed that SDH genetic testing, including tests for large genomic deletions, is indicated in all patients with head and neck and/or thoracic-abdominal or pelvic paraganglioma and can be targeted according to clinical criteria.
Read the PubMed abstract

To read more about "Hereditary pheochromocytoma-paraganglioma syndrome"

J Clin Endocrinol Metab ; 2817-2827 ; August 2009
Degenerative ataxias: patient involvement in health research
To incorporate patient perspective in the design of a systematic review of scientific literature on the effectiveness of degenerative ataxias (DA) treatments, 53 patients with DA from different regions of Spain were consulted. The most relevant self-perceived health problems were limitations in activities of daily living (ADL), visual and auditory problems and diminished self-esteem. The bibliographic search for the systematic review was enriched by these patient contributions. No study offered information on treatment effectiveness for the following problems prioritised by patients: ADL, social relationships, disease acceptance and quality of life. Thus some of the self-perceived DA-related health problems identified by the patients have never been investigated and should be considered to improve future research projects which should be adapted to meet patient needs.
Read the PubMed abstract

Soc Sci Med ; 920-925 ; September 2009
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis: clinical signs in children and adolescents
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is increasingly recognised in children, comprising 40% of all cases. Younger patients are less likely to have tumours. Behavioural and speech problems, seizures, and abnormal movements are common early symptoms. The phenotype resembles that of the adults, although dysautonomia and hypoventilation are less frequent or severe in children. In this study of 81 patients, 74% had full or substantial recovery after immunotherapy or tumour removal. Neurological relapses occurred in 25%. At the last follow-up, full recovery occurred more frequently in patients who had a teratoma that was removed (5/8) than in those without a teratoma.
Read the PubMed abstract

Ann Neurol ; 11-18 ; July 2009
Hereditary defects of primary bile acid synthesis: oral cholic acid is a safe and effective long-term therapy
Oral bile acid replacement has been shown to be an effective therapy in primary bile acid synthesis defects. To evaluate the long-term effectiveness and safety of cholic acid (CA) therapy, fifteen patients with either 3beta-hydroxy-Delta(5)-C(27)-steroid oxidoreductase) or Delta(4)-3-oxosteroid 5beta-reductase deficiency received oral CA and were followed up prospectively. Oral CA therapy was shown to be a safe and effective long-term treatment of the most common primary bile acid synthesis defects.
Read the PubMed abstract

To read more about "Anomaly of bile acid synthesis"

Gastroenterology ; 1310-1320 ; October 2009
Legg-Calve-Perthes disease: systemic effects of zoledronic acid in children
Legg-Calve-Perthes disease (LCPD) is the term used to describe uni- or bilateral avascular necrosis (AVN) of the femoral head in children. Intravenous bisphosphonate therapy is associated with preservation of femoral head sphericity and congruence in 77% of children with traumatic avascular necrosis. To describe the systemic effects of intravenous zoledronic acid (ZA) on bone and mineral metabolism in otherwise normal children and adolescents with femoral head AVN, 37 children diagnosed with avascular necrosis AVN were treated with at least 12 months of ZA. ZA increased bone mineral density and reduced bone modelling and turnover. Further efficacy and safety data are required before this therapy can be widely recommended.
Read the PubMed abstract

To read more about "Legg-Calve-Perthes disease"

Bone ; 898-902 ; November 2009
Primary systemic AL amyloidosis: weekly and twice-weekly bortezomib dosages appear tolerated
New treatment options are required for primary systemic AL amyloidosis (AL). This phase 1 dose-escalation component of a phase 1/2 study in relapsed AL aimed to determine the maximum tolerated dose of bortezomib once weekly and twice weekly and assess preliminary hematologic responses in 31 patients. Most commonly reported toxicities on both schedules included gastrointestinal events, fatigue, and nervous system disorders. Discontinuations and dose reductions for toxicity were reported in 12 and 4 patients, respectively. No treatment-related deaths occurred. Hematologic responses occurred in 15 of 30 evaluable patients, including 6) complete responses. Once-weekly and twice-weekly bortezomib appear generally well tolerated in relapsed AL, with promising hematologic responses.
Read the PubMed abstract

To read more about "Amyloidosis, primary"

Blood ; 1489-1497 ; 20 August 2009
Amyotrophic lateral sclerosis: neither valproic acid nor coenzyme Q10 prove beneficial
To determine whether valproic acid (VPA), a histone deacetylase inhibitor that showed antioxidative and antiapoptotic properties and reduced glutamate toxicity in preclinical studies, is safe and effective in amyotrophic lateral sclerosis (ALS) using a sequential trial design, 163 ALS patients received VPA 1,500mg or placebo daily. The study revealed that VPA, at a dose used in epilepsy, does not show a beneficial effect on survival or disease progression in patients with ALS. A separate phase II trial administering coenzyme Q10 for ALS did not show benefits either.
Read the PubMed abstract
Read the PubMed abstract

To read more about "Amyotrophic lateral sclerosis"

Ann Neurol ; 227-234 ; August 2009
Ann Neurol ; 235-244 ; August 2009

Congenital aromatase deficiency: the effects of long-term raloxifene and estradiol treatments on bone
In adult aromatase-deficient men, estrogen treatment has always resulted in a rapid skeletal maturation with epiphyseal closure and improved BMD. Raloxifene is a SERM with proven estrogen agonist action on bone that leads to an improvement in BMD and a reduction in bone turnover. The present study reports the effects of raloxifene and transdermal estradiol treatment, respectively, on epiphyseal closure and BMD in one aromatase-deficient man, over a 24-month follow-up. The results show that the management of aromatase deficiency in the male cannot consider raloxifene as a first choice treatment, but should be still based on estrogen replacement treatment since in this patient the completion of bone maturation has only been obtained once estradiol substitution was performed. The present case also demonstrates that raloxifene is able to improve BMD in aromatase-deficient men.
Read the PubMed abstract

To read more about "Aromatase deficiency"

Bone ; 827-832 ; November 2009

Orphan Drugs
FDA issues an early communication for chronic anaemia and iron overload treatment Exjade
In the USA, the Food and Drug Administration is reviewing adverse event information for iron chelating agent deferasirox (marketed as Exjade) from a database that tracks all patients who are prescribed Exjade and a company-sponsored global safety database. Data suggest that there could be an increased risk for adverse events - kidney failure, gastrointestinal haemorrhage and death - in those patients with myelodysplastic syndrome. For further information
First drug for peripheral T-cell lymphoma approved in the USA
The U.S. Food and Drug Administration has approved Folotyn (pralatrexate), the first treatment for rare cancer peripheral T-cell lymphoma, an often-aggressive form of non-Hodgkins lymphoma. Folotyn was approved under the FDA’s accelerated approval process for patients who have relapsed, or have not responded well to other forms of chemotherapy. In a press release, Richard Pazdur, M.D., director of the Office of Oncology Drug Products in the FDA’s Center for Drug Evaluation and Research, observed that “Folotyn’s approval demonstrates FDA’s commitment to the rapid approval of drugs for rare and uncommon diseases”.
FDA approves treatment for abdominal attacks and facial swelling associated with hereditary angioedema
The U.S. Food and Drug Administration has approved the first treatment for acute abdominal attacks and facial swelling associated with rare and potentially life-threatening genetic disease hereditary angioedema. Berinert (C1 esterase inhibitor), manufactured by CSL Behring (Marburg, Germany) is a protein product derived from human plasma that regulates clotting and inflammatory reactions. Berinert received marketing authorisation in France in March 2009.

Partnersearch, Job Opportunities
Job opportunity in translational neuromuscular research available in Newcastle, UK
An opportunity for training in translational medicine is available in the Newcastle Muscle Centre, UK, via an award scheme funded by the Wellcome Trust. The four-year training programme will include a year of taught courses around the many issues of drug development and trial design, followed by a three year PhD project. Industry and academic leads deliver the courses and the PhD programmes also have industry components, providing a broad education in the field of drug development and translational medicine. The successful applicant will be based in the Newcastle muscle team, and will be able to take part in clinical, research and TREAT-NMD activities within the centre. This is a full-time salaried position on a Clinical Research Associate salary scale (currently £27,523 - £46,426, although more senior candidates could be appointed to a higher scale). Applicants must be eligible for General Medical Council registration in the UK as well as being able to fulfil residency requirements.
For more details


News from the Patients' Associations
Europe and USA rare disease advocacy groups reach across the Atlantic to form common alliance
Following in the footsteps of the FDA and the EMEA, a transatlantic alliance has now been forged to strengthen and share resources for rare disease patients. The European Organisation of Rare Diseases (EURORDIS ) and the USA’s National Organization of Rare Disorders (NORD) have signed a Memorandum of Understanding designed to coordinate and pool efforts and resources. The strategic partnership between the two groups will harmonise key advocacy priorities, allowing for the coordination of biopharmaceutical-related activities. In a press release, Peter L. Saltonstall, NORD President and CEO, commented that “Since patients with rare diseases may be located anywhere in the world, international collaboration to support and advance their needs is extremely important”. EURORDIS Chief Executive Officer Yann Le Cam concurred, observing that the two advocacy groups are well-positioned to “…help bridge the gap between those regions of the world that have progressed more than others in their strategies to address the needs of people living with rare diseases. We can be key facilitators to promote the common interest of people with rare diseases and to empower patient advocates all over the world."
First European cystic fibrosis week elicits participation from 33 countries

CF Europe, a federation of national European cystic fibrosis associations and a subdivision of Cystic Fibrosis Worldwide, is organising the first European Cystic Fibrosis Awareness Week to highlight issues surrounding this monogenic illness characterised by alterations in the CFTR protein that change the characteristics of exocrine excretions. An absence of functional CFTR in the epithelial cell membrane leads to the production of sweat with a high salt content, associated with a risk of hyponatremic dehydration, and mucus secretions with an abnormal viscosity, leading to stasis, obstruction and bronchial infection. From 9-15 November 2009, patient associations in 33 European countries will participate with CF Europe in a week of awareness. Participants would like to see equitable access to early diagnosis, regular follow-up by specialists, proper hygiene and adequate treatment. Basic treatments are not available in several countries, and even in countries with better developed care, cystic fibrosis patients still have a lower life expectancy. Thus the associations are calling for optimal care and quality of life for all countries, pointing out that such measures not only prolong and save human lives - they also ultimately save extra health costs. For further information


What's on Where?
Applications of cell and gene therapy for the treatment of genetic instability disorders
Date: 12-13 November 2009
Venue: Madrid, Spain

This meeting will bring together specialists from around the world to focus on advances in cell and gene therapy for the treatment of genetic instability disorders. Presentations include gene therapy strategies for rare genetic diseases and discussions of specific disorders such as dyskeratosis congenita and Werner syndrome.
For further details

TREAT-NMD/NIH International Conference
Date: 17-19 November 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

OI in motion: Rehabilitation and Physiotherapy in Osteogenesis Imperfecta
Date: 20-22 November 2009
Venue: Rheinsberg, Germany

Topics include: Rehabilitation of children; rehabilitation of adults; assessments of motor functions; orthoses/mobility aids; and international experiences.
For further details

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

A conference of the European Science Foundation. The meeting will bring together experts in sensory neuroscience, developmental biology, genetics, cell biology, modelling, translational research and therapy. It aims at promoting exchanges between the scientists of the two fields and beyond, at stimulating the emergence of new research projects at the interface between disciplines and at training young researchers in this interdisciplinary field.
For further details

International Conference on Myasthenia
Date: 1-2 December 2009
Venue: Paris, France

The conference will bring together research scientists and clinicians from around the world who specialise in myasthenia, to review the latest developments, exchange experiences and ideas, and broaden knowledge and understanding of this rare disease. A session dedicated to the interaction between clinicians, scientists, and patient associations is also scheduled.
For further details

Meeting of the International Society of Neonatal Screening and Latin American Society of Inborn Errors of Metabolism
Date: 6-9 December 2009
Venue: Cancun, Mexico

For the first time the International Society of Neonatal Screening and the Latin American Society of Inborn Errors of Metabolism join forces to host the seventh International and Latin American Congress on Inborn Errors of Metabolism and Neonatal Screening, an academic event aimed to foster the interchange of new ideas and experiences in the fields of inborn metabolic diseases and neonatal screening.
For further details

2010 Neuromuscular Disorders Conference: Toward a Better Future
Date: 26-27 February 2010
Venue: Sydney, Australia

Featuring a stimulating and progressive programme disseminating the most recent research in the field of neuromuscular conditions, this conference will provide an exciting poster session where up and coming researchers will have an opportunity to present their research to the neuromuscular community.
For further details

2nd Pan-European Conference on Haemoglobinopathies
Date: 13-14 March 2010
Venue: Berlin, Germany

This conference aims to further strengthen the national and regional support networks for thalassaemia patients in Europe, and increase awareness among European medical professionals and national health authorities of the disorder, its proper management and prevention.
For further details

6th International Conference on Rare Diseases and Orphan Drugs
Date: 18-20 March 2010
Venue: Buenos Aires, Argentina

The 6th International Conference on Rare Diseases and Orphan Drugs (ICORD 2010) for the first time will be convened in the southern hemisphere in agreement with its aim of globalisation of rare disease research and orphan products development activities.
For further details

ASA-EHA Conference: Innovative Therapies for Red Cell and Iron Related Disorders
Date: 16-18 April 2010
Venue: Cascais, Portugal

Sessions include: Hematopoietic stem cell therapies; molecular switching in erythroid differentiation; gene therapy; iron regulatory pathway for therapies; innovative therapies for red cell disorders, and more.
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.

BHD Symposium 2010 for Birt-Hogg-Dubé Syndrome
Date: 22 April 2010
Venue: Washington, DC USA

A symposium for reviewing the latest developments for Birt-Hogg-Dubé syndrome.
For further details

5th European Conference on Rare Diseases 2010
Date: 13-15 May 2010
Venue: Crakow, Poland

Details will be available soon.

22nd Annual Meeting of the European Academy of Childhood Disability
Date: 27-29 May 2010
Venue: Brussels, Belgium

This year’s event - Measures of Progress – Evaluating management outcome in childhood disability - will update and clarify the multidimensional model of disablement specifically applied to management of children with neurodevelopmental disability. Emphasis is on the need for reliable measurement of management outcomes through new findings, from functional imaging to quality of life assessment. Deadline for abstract submission: 1 February 2010
For further details

European Human Genetics Conference 2010
Date: 12-15 June 2010
Venue: Gothenburg, Sweden

In conjunction with the European Meeting on Psychosocial Aspects of Genetics. Deadline for abstract submission: 19 February 2010
For further details

14th International Conference on Behçet Disease
Date: 8-10 July 2010
Venue: London, England

Presenting new developments in basic and clinical science to bear on the specific issues of Behçet Disease (BD). Topics to be covered will include immunology of BD, vasculitis in BD, genetic basis of BD, regional inflammation and paediatric BD. The programme will also include debates on topics of current interest or controversy. Deadline for abstract submission: 31 March 2010
For further details

Men 2010: 12th International Workshop on Multiple Endocrine Neoplasia
Date: 16-18 September 2010
Venue: Viareggio, Italy

This two-day meeting will provide a forum for educating basic and clinical investigators on the most recent advances in the area of hereditary endocrine tumours. Deadline for abstract submission: 7 June 2010
For further details


Press & Publications

A batch of publications from EUROCAT in 2009
EUROCAT, the European network of population-based registries for the epidemiologic surveillance of congenital anomalies, has issued several publications this year. The list includes an article appearing in the Lancet entitled What is the "Primary" Prevention of Congenital Anomalies? and two EUROCAT special reports: Congenital Heart Defects in Europe, 2000-2005 and The Status of Health in the European Union: Congenital Malformations. Another in-house publication is the EUROCAT Statistical Monitoring Report 2006. EUROCAT also contributed to an article appearing in the European Journal of Paediatric Urology entitled Congenital Hydronephrosis: Prenatal Diagnosis and Epidemiology in Europe, and produced a report published in the British Journal of Gynaecology entitled Maternal Age-Specific Risk of Non-Chromosomal Anomalies.
Consult the list of 2009 EUROCAT publications


Orphanews Europe, the newsletter of the Rare Diseases Task Force
Orphanews Europe is supported by the European Commission's DG SANCO
and the French Muscular Dystrophy Association (AFM)
Editor-in-chief: Ségolène Aymé
Editor: Louise Taylor
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Editorial Board: Ségolène Aymé, Catherine Berens, Olaf Bodamer, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Annie Olry, 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)
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