17 September 2008 print
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Integrating Orphanet with other major databases: a step forward
Orphanet is now well-established as the documentary resource for rare diseases. Its directory of 5,857 rare diseases is most often used by health professionals but also by patients and families and by researchers who all together consult over 20,000 pages every day. As part of its partnership with EuroGentest, the EC funded Network of Excellence dedicated to quality testing in Europe, Orphanet has added new functions to its website, designed to better serve biologists and researchers. Through the enhancement of information on genes associated with rare diseases, Orphanet now offers the possibility to query by gene when searching for a clinical laboratory to perform a specific test. It also now presents the possibility to find information on research activities linked to specific genes.

By cross-referencing a gene with each rare disease to which it is associated, Orphanet provides a search option that allows users to easily capture all genes linked to a particular disease or all diseases linked to a particular gene. To access this service, click on the “rare diseases” tab on the front page, followed by the “gene” sub-tab that appears.

Orphanet has also integrated the other leading scientific databases for genetics to facilitate smooth navigation between them. It is thus now possible to access additional information on a particular gene via OMIM, Genatlas, HGNC and Swissprot – all from Orphanet’s gene page. Enjoy this new service!

Further information on the cross-referenced databases

Spotlight on...
ECORN-CF: An interactive information service for cystic fibrosis…
“where the information travels, not the patient”


Cystic fibrosis is the most common potentially-fatal genetic disorder among Caucasian children. It is a monogenic autosomal recessive disease characterised by alterations in the CFTR protein, which regulates transmembrane hydroelectrolytic flux. An absence of functional CFTR in the epithelial cell membrane leads to the production of sweat with a high salt content and mucus secretions with an abnormal viscosity leading to stasis and obstruction in various organs. The exact prevalence of cystic fibrosis in Europe is unknown, but estimates range between 1/8 000 and 1/10 000 individuals. The incidence at birth varies between populations, and lies between 1/2 500 to 1/5 000 newborns. The disease is chronic and generally progressive, with onset usually occurring during early childhood. Virtually any internal organ may be involved but the principle manifestations concern the respiratory apparatus (chronic bronchitis due to an increased susceptibility for bacterial infection), pancreas (pancreatic insufficiency, adolescent diabetes and occasionally pancreatitis), the intestine and liver (cirrhosis). The most common form is associated with chronic respiratory infections, digestive problems and impaired growth. Mortality and morbidity in most cases depend on the extent of the bronchopulmonary involvement. Male sterility is a constant feature.

In 2006, the pilot project European Centres of Reference Network for Cystic Fibrosis (ECORN-CF) was selected for funding under the EU 2003-2008 public health action programme, which prioritises the development of European Networks of Reference Centres for Rare Diseases. The idea for this internet-based expert advice resource for cystic fibrosis (CF) originated in Germany. With support both from the European Commission (DG Sanco) as well as the Christiane Herzog Stiftung trust (created by the former German First Lady), this initiative, intended to provide expert advice via the Internet, has been able to expand to other countries in the EU. The scope of its audience includes patients and their families, physicians, physiotherapists, nurses, dieticians, pharmacists, social workers and anyone else who needs specific information relating to cystic fibrosis. At present nine associated partner EU countries participate in ECORN-CF, representing eight language zones (Czech, Dutch, English, German, Lithuanian, Polish, Romanian, and Swedish), represented by 16 care teams and patient groups. Collaborating organisations are located in Cyprus, Denmark, Finland, France, Greece, Italy, Hungary, Norway, Portugal, Slovakia, Spain, Switzerland and Turkey. The project, led by Thomas Wagner, professor in pulmonary medicine (Frankfurt, Germany), has seven distinct work packages: Coordination of the project; Dissemination of the results; Evaluation of the project; Expert advice to CF-patients and other lay people; Expert advice to members of the CF care team; Quality assurance program; Evaluation of the impact of the program on quality of care and implementation of the guidelines.

ECORN-CF for the patient

When CF patients or their families have a question about the illness, they no longer have to wait for the next appointment with their doctor or nurse, but can post their question via the ECORN-CF Internet website and receive an answer from an expert team. All questions and answers remain accessible in the local language in an archive on the local ECORN-CF website. For the sites that are frequently visited, many answers can be found immediately in the archive along with answers provided by the CF experts. In time, the accumulated questions and responses can be used to form an internet–encyclopaedia reference.

…and for the professional

In CF practice questions can arise that are not easily answered. With ECORN-CF, health professionals have the opportunity to ask questions via the Internet and receive an answer from the special CF expert team. When the local team cannot answer a question, it will seek aid from the ECORN-CF collaborating partners. These questions and answers are also archived on the website, but are not available to the lay public.

A multilingual resource

Currently it is possible to pose questions and receive answers in Czech, Dutch, English, German, Lithuanian, Polish, and Romanian. All questions and answers are translated into English for storage in the archives and for quality evaluation purposes. They are accessible from the ECORN-CF Archive. On every local site (e.g. Czech) there is a link to the ECORN-CF Archive located at the top of the local website homepage. It is hoped that this feature will eventually be made available to more people in more languages of the European member states.

To pose a question, one enters the ECORN-CF portal and selects the language desired. Questions can be asked either anonymously or after registering with a personal log-in. Before sending in a question it is advisable to first search the local questions and answers page and (if the questioner is able to understand English) the Ecorn-CF Archive to check whether the answer is already there. The questions already posted are freely accessible. It is necessary to log-in to check the answers to these questions.

Starting a quality ECORN-CF service in another European language

Since one of the aims of the whole ECORN-CF project is the establishment of easier access to high quality information in all European member states, inquiries concerning new languages are especially welcome by the current ECORN-CF team, who will aid new members develop a new language site, as well as help manage the web service and the quality assurance programme, et cetera. In order to launch a local ECORN-CF site, it is necessary to identify CF professionals willing to serve as part of an expert team in the language of the new site. Aside from offering their advice on the net, they must be willing to translate questions and answers into the English language for the English language archives and for quality control measures. To make sure that the advice offered by local ECORN-CF experts meets the highest quality standards, every answer is reviewed for quality and adherence to European guidelines and/or consensus. All questions and answers are thus translated into English and then evaluated by the European Expert team. This quality management programme in conjunction with additional quality round table meetings ensure that all contributing experts are trained to the highest possible level of expertise.

The interactive quality-based informational system of ECORN-CF can easily be applied to other rare diseases.

Contact ECORN-CF


EU Policy News
The EC proposal for a directive on cross-border healthcare:
Article 15 promotes quality reference networks

In the last issue of OrphaNews Europe, we reported on the EC adoption of a directive proposal on cross-border health care. This proposal delineates relevant legal definitions and general provisions and sets up a framework for cross-border healthcare based on the establishment of common principles in EU health systems and on European cooperation. Article 15 of the directive (found in chapter IV) is of particular pertinence to rare disease care – it promotes the development and coordination of European reference networks. Specifically, the measure calls upon member states to facilitate European reference network development in order to make available care for those patients with a condition “requiring a particular concentration of resources or expertise”. Article 15 promotes quality and is designed to aid those member states that have an “insufficient number of patients with a particular condition” or that lack expertise or technology for a particular condition. It defines the elements a reference network must be able to provide, including diagnostics, management, follow-up, and expert advice, and presents a list of criteria a network would need to fulfil. The cross-border directive proposal next passes through a co-decision process involving the Council of Ministers and the European Parliament. Once a decision is taken, the member states will have one year to implement the directives of the proposal.
Is there a need for centres of expertise for bleeding disorders in Europe?
The European Haemophilia Consortium (EHC) organised a Round Table in July to examine whether networks of expertise for bleeding disorders would be beneficial at the European level. Some 25 participants from the fields of medicine, science, government, industry and patient associations took part in the discussion, including members of the EC Rare Disease Task Force. The meeting unveiled a “clear consensus” that cooperation amongst existing centres for haemophilia and other bleeding diseases would facilitate the “mobility of knowledge” that could improve the quality of care in individual centres across Europe. There are currently diverse structures specialising in haemophilia care in Europe. Consolidating these centres via a network would strengthen competences and allow for the dissemination of information. Many issues remain to be hashed out, including setting clear criteria and scope for bleeding disorder centres of expertise; the question of international accreditation; and the possibility of a proposal for an EU funded pilot project to develop the network of centres of expertise. There is already a network established at the European level, the Rare Bleeding Disorders Database, which serves as an international information source, gathering prevalence, clinical, genetic and therapeutic data. The next EHC policy Round Table is scheduled for early October and has on the agenda the topic of disparities in haemophilia care and how to reduce discrepancies across Europe.
EU launches pilot project testing free access to funded research results
The European Commission in August launched a test project that calls for unrestricted free access to EU-funded research results via the Internet, despite protests from scientific publishers standing to lose on the deal. Under the pilot scheme, peer-reviewed scientific journal articles stemming from EU-funded research projects would have to be freely accessible to the general public following an initial embargo period of 6-12 months. The pilot project covers 20% of the EU Seventh Framework Programme budget and is applicable to the area of health, amongst other fields. The project evolves from an EC Communication issued in February 2007 on the topic of access to research in the digital era. The Commission believes that open access to research results will ultimately enhance European-level research and that the public has the right to access publicly-funded research results. The pilot project is to be implemented via a clause contained in funding agreements issued under the EU Seventh Framework Programme scheme requiring grant recipients to deposit peer-reviewed research articles or final manuscripts resulting from FP7 projects into a repository from their institution. A study of the impact of free access on scientific publishers was conducted by the EC in 2006. But the International Association of Scientific, Technical and Medical Publishers (STM) pointed out in a declaration issued in response to the study that “articles have economic value for a considerable time after publication... At 12 months, on average, electronic articles still have 40-50% of their lifetime downloads to come. Free availability of significant proportions of a journal’s content may result in its cancellation and therefore destroy the peer review system upon which researchers and society depend”. Rare disease and orphan drug research projects fall under the second pillar of the FP7 Health theme in collaborative research: translating research for human health. Several rubrics are applicable to rare disease research, including those on natural history studies, patho-physiology, and the development of preventive, diagnostic and therapeutic approaches. There is also some crossover between other rubrics included under the health theme, such as high-throughput research, or the development of innovative therapeutic approaches and interventions, including gene and cell therapies.
DG Research
FP7 Health Call for Proposals
Under the Seventh Framework Programme of the European Commission’s DG Research, two calls for proposals were announced on 3 September. Amongst the areas of the FP7-Health-2009-single-stage call are topic 2.4.4-1: Rare neurological diseases; and topic 2.4.4-2: Preclinical development of substances with a clear potential as orphan drugs. Both the FP7-Health-2009-single-stage call and the FP7-Health-2009-two-stage call have preliminary deadlines of 3 December 2008.
For further information.

Call for Experts
The European Commission call for the establishment of a database of independent experts to assist the Commission's services for tasks in connection with the Seventh Framework Programme (FP7) is still open. Should you wish to express your interest for participating in future FP7 evaluation, review and/or monitoring tasks, you are welcome to register here.
For more information


National & International Policy Developments
Other European news
Italy hosts rare disease art and prose competition
The Italian National Center for Rare Diseases is organising its first literary and art competition dedicated to rare diseases, entitled Il volo di Pègaso (the Flight of Pegasus). Submissions are welcome in six sections: prose, poetry (both in Italian language), drawing, painting, sculpture and photography. The competition is open to artists of all nationalities and ages. Selected works will be presented at an exhibition during the next European Rare Disease Day. Monies collected will be used to finance a fellowship in the field of rare diseases.
For further information (in Italian).

Other International News
Olympic hopeful doesn’t let Behcet disease stop her in China
American 400-meter track and field athlete Sanya Richards won a bronze medal on 19 August and helped the 1600 meter relay team take the gold less than a week later. Sanya Richards, a 23-year-old originally from Jamaica, was diagnosed with Behcet disease in 2007, a systemic inflammatory disease, characterised by painful lesions in the mouth, skin and genitals, and which can also affect the eyes, brain and vascular and digestive systems. Sanya Richards, who won a gold medal for the 400 meter race in 2004, had her performance temporarily impaired by the disease in 2007, which she described as feeling “flu-like”, but bounced back later in the year to qualify for the World Championships. Besides her athletics training and performance, Sanya works with the American Behcet Disease Association (ABDA), raising awareness for the disease.
Could a recent US ruling obliging company to include patient in trial hurt future rare disease clinical research?
In the USA, a federal judge in August ordered the start-up pharmaceutical company PTC Therapeutics to furnish a terminally ill 16-year-old Duchenne muscular dystrophy (DMD) patient with PTC124, an experimental treatment that restores production of full-length, functional proteins in cases of the disease caused by nonsense mutations (an estimated 13% of DMD cases). According to the company, the patient is ineligible to participate in a 96-week phase II trial for the drug that is set to begin because he did not participate in a preliminary trial. The company states that the patient’s participation would not be safe and would furthermore set a precedent that could hinder research. The patient’s family, however, contending that the patient was assured that he could participate in the phase II trial, is calling upon the FDA Compassionate Use act in order to oblige PTC Therapeutics to provide the treatment. In a statement published on the company website, PTC Therapeutics president and CEO Stuart Peltz evoked the possible scenario emerging from the decision where “no patients will want to participate in our current clinical trials in which they might receive a placebo rather than PTC124”.
Read the judge’s opinion on the case


Ethical, Legal & Social Issues
Lost in translation: A British study underscores difficulties in communicating genetic test information to non-native speakers
As western countries become increasingly multicultural - and multilingual - the task of communicating medical information accurately can be arduous, particularly in rare disease genetic testing, a field already beset by concepts and terminology that are often complex and shaded with nuance. A study funded by the Economic and Social Research Council (ESRC) examined the British Bangladeshi community’s understanding of information relating to prenatal genetic testing. The researchers found that language differences contribute to misunderstanding the nature and cause of genetic disorders. In the study, the authors cite difficulties patients had in discerning between being “affected” and being a “carrier”, understanding abbreviations, and following treatments. Interpreters can be helpful, although some terms and concepts do not exist in all languages and thus continue to pose difficulties. The repercussions of this communication gap are significant. In prenatal testing, the decision of whether or not to terminate a pregnancy is dependent on a clear understanding of the information conveyed. Women who speak little English and rely on a family member to interpret the test results may be receiving information that is incomplete, incorrect or misunderstood. The report found that misunderstandings are also fairly common even amongst those receiving information in their native language.
European pharmaceutical group implements code of practice for interactions with patient groups
The European Federation of Pharmaceutical Industries and Associations (EFPIA), representing over 2000 companies via more than 30 national associations and 40 individual corporations, including the European Biotechnology Enterprises (EBE), has announced the implementation of a Code of Practice to guide relations between industry members and European patient organisations. Under the terms of the code, which came into effect on 1 July, companies must make publicly available the names of patient groups to which support – financial or otherwise – is proffered and define the exact nature of this support. The information must be published on the company website or other suitable venue by the end of March 2009. The EFPIA, which defines its mission as improving “the competitiveness of the research-based pharmaceutical industry in Europe in a regulatory and political environment, which above all stimulates R&D and rewards innovation” has developed the code to build upon certain previously determined principles: that patient organisation independence (in terms of political judgements, activities and policies) is maintained; that patient groups and industry have partnerships defined by mutual respect and equality; that no prescription-only medicine shall be promoted by a patient organisation and industry will not request otherwise; that partnerships will be transparent, with financial support provided by industry openly acknowledged; and that the broad funding of patient organisations from multiple sources is to be welcomed. In a press release, EFPIA president and Bayer Health Care CEO Arthur Higgins called the code, “an important milestone in the industry’s efforts to be recognised as a trustworthy partner in healthcare solutions”. Adherence to the code is to be monitored at the national level and must include a mechanism for reviewing complaints. Patient organisations play a particularly important and active role in the field of rare diseases.
Consult the Code of Practice


Orphanet News
New Texts
New Orphanet publications
Prader–Willi syndrome (published in the European Journal of Human Genetics, in association with Orphanet)

PTEN hamartoma tumor syndromes (published in the European Journal of Human Genetics, in association with Orphanet)


New Genes
Sarcoidosis: Study identifies ANXA11 as a new susceptibility locus
Sarcoidosis is a complex chronic inflammatory disorder with predominant manifestation in the lung. In the first genome-wide association study of this disease, comprising 499 German individuals with sarcoidosis and 490 controls, the authors detected a series of genetic associations. The strongest association signal maps to the ANXA11 gene (annexin A11) on chromosome 10q22.3. Extensive fine mapping located the association signal to a region between exon 5 and exon 14 of ANXA11. Annexin A11 has complex and essential functions in several biological pathways, including apoptosis and proliferation.
Read the PubMed abstract

Nat Genet ; Epub ahead of print ; 10 August 2008
Addison disease: An association found with the 1858T-allele of PTPN22
The PTPN22 gene was recently identified as an important genetic susceptibility factor in several autoimmune diseases. The increased risk has been broadly explained by the 1858T-allele. As two smaller studies on Addison disease (AD) have shown diverging results, the authors aimed to elucidate the predisposing effect of the single-nucleotide polymorphism (SNP) 1858CT in a larger population of AD patients, especially focusing on the AD patients with known autoimmune etiology. They also screened for unknown rare or common variants in the PTPN22 gene that could predispose for AD. The case-control study of 332 Norwegian AD patients and 990 controls showed a significant association between autoimmune AD and the PTPN22 1858T risk allele. The association of AD with 1858T was supported by a meta-analysis combining genotype data with that of others published previously. Other rare variants in PTPN22 do occur, and may also be involved in the pathogenesis.
Read the PubMed abstract

Eur J Hum Genet ; 977-982 ; August 2008
Joubert syndrome: Mutations in the cilia gene ARL13B lead to the classical form of the disease
Joubert syndrome (JS) and related disorders are a group of autosomal-recessive conditions sharing the "molar tooth sign" on axial brain MRI, together with cerebellar vermis hypoplasia, ataxia, and psychomotor delay. JS is suggested to be a disorder of cilia function and is part of a spectrum of disorders involving retinal, renal, digital, oral, hepatic, and cerebral organs. The authors identified mutations in ARL13B in two families with the classical form of JS. ARL13B belongs to the Ras GTPase family, and in other species is required for ciliogenesis, body axis formation, and renal function. The encoded Arl13b protein was expressed in developing murine cerebellum and localized to the cilia in primary neurons. Overexpression of human wild-type but not patient mutant ARL13B rescued the Arl13b scorpion zebrafish mutant. Thus, ARL13B has an evolutionarily conserved role mediating cilia function in multiple organs.
Read the PubMed abstract

Am J Hum Genet ; 170-179 ; August 2008
Autism: Convergent evidence identifies MARK1 as a susceptibility gene
Autism spectrum disorders (ASDs) are common, heritable, but genetically heterogeneous neurodevelopmental conditions. The authors recently defined a susceptibility locus for ASDs on chromosome 1q41-q42. High-resolution single-nucleotide polymorphisms (126 SNPs) genotyping across the chromosome 1q41-q42 region, followed by a MARK1 (microtubule affinity-regulating kinase 1)-tagged-SNP association study in 276 families with autism from the Autism Genetic Research Exchange, showed that several SNPs within the MARK1 gene were significantly associated with ASDs by transmission disequilibrium tests. They found that MARK1 was overexpressed in the prefrontal cortex but not in cerebellar granule cells, on postmortem brain tissues from patients. MARK1 displayed an accelerated evolution along the lineage leading to humans, suggesting possible involvement of this gene in cognition. MARK1 encodes a kinase-regulating microtubule-dependent transport in axons and dendrites.
Read the PubMed abstract

Hum Mol Genet ; 2541-2551 ; 15 August 2008

Research in Action
Fundamental Research
Marinesco-Sjögren syndrome: Novel SIL1 mutations and exclusion of functional candidate genes
Marinesco-Sjögren syndrome(MSS) is a rare autosomal recessively inherited neurodegenerative disorder characterised by cerebellar ataxia, cataracts, mental retardation, and progressive myopathy. Recently, mutations in the SIL1 gene, which encodes an endoplasmic reticulum (ER) resident cochaperone, were identified as a major cause of MSS. The authors here report four novel mutations in SIL1, including the first missense substitution described for the disease. In addition, they excluded three functional candidate genes.
Read the PubMed abstract

Eur J Hum Genet ; 961-969 ; August 2008
Joubert syndrome: Huntingtin-associated protein 1 interacts with Ahi1 to regulate cerebellar and brainstem development in mice
Joubert syndrome is an autosomal recessive disorder characterised by congenital malformation of the cerebellum and brainstem, with abnormal decussation in the brain. Mutations in the Abelson helper integration site 1 gene, which encodes the protein AHI1, have been shown to cause Joubert syndrome. In this study, the authors found that mouse Ahi1 formed a stable complex with huntingtin-associated protein 1 (Hap1), which is critical for neonatal development and involved in intracellular trafficking. Hap1-knockout mice showed significantly reduced Ahi1 levels, defective cerebellar development, and abnormal axonal decussation. Suppression of Ahi1 also decreased the level of Hap1; and truncated Ahi1, which corresponds to the mutations in Joubert syndrome, inhibited neurite outgrowth in neuronal culture.
Read the PubMed abstract

J Clin Invest ; 2785-2795 ; August 2008
Potocki-Lupski syndrome: Abnormal social behaviours and altered gene expression rates in a mouse model
Potocki-Lupski syndrome (PTLS) is associated with a microduplication of 17p11.2. Clinical features include multiple congenital and neurobehavioral abnormalities and autistic features. The authors generated a PTLS mouse model that recapitulates some of the physical and neurobehavioral phenotypes present in patients. In this study they investigated the social behaviour and gene expression pattern of this mouse model.
Read the PubMed abstract

Hum Mol Genet ; 2486-2495 ; 15 August 2008
Smith-Magenis syndrome: Phenotypic consequences of Rai1 dosage in mice
The retinoic acid induced 1 (RAI1) gene when deleted or mutated results in Smith-Magenis syndrome (SMS), while duplication of 17p11.2, including RAI1, results in the dup(17)(p11.2) syndrome characterised by mental retardation, growth and developmental delays, and hyperactivity. The authors have created and evaluated mice with a graded series of four (hemizygous) and six (homozygous) copies of Rai1, and overexpressing Rai1>1.5-fold and >2-fold, respectively. Data show that Rai1-transgenic mice have growth retardation, increased locomotor activity, and abnormal anxiety-related behaviour. Rai1-transgenic mice also have an altered gait with short strides and long sways, impaired ability on a cage-top hang test, decreased forelimb grip strength, and a dominant social behavior. Further, analyses of homozygous transgenic mice revealed a dosage-dependent exacerbation of the phenotype, including extreme growth retardation, severe neurological deficits, and increased hyperactivity. These results show that Rai1 dosage has major consequences on molecular processes involved in growth, development, and neurological and behavioral functions, thus providing evidence for several dosage-thresholds for phenotypic manifestations causing dup(17)(p11.2) syndrome or SMS in humans.
Read the PubMed abstract

Eur J Hum Genet ; 941-954 ; August 2008
Clinical Research
Juvenile idiopathic arthritis: A comprehensive review of the genetics
Juvenile idiopathic arthritis (JIA) is believed to be influenced by both genetic and environmental factors. The progress in identifying genes underlying JIA susceptibility using candidate gene association studies has been slow. In this review the authors discuss the principles behind genetic studies of complex traits like JIA, and comprehensively catalogue non-HLA candidate-gene association studies performed in JIA to date and review several validated associations.
Read the PubMed abstract

Pediatr Rheumatol Online J ; 6: 11 ; 21 July 2008
Epiphyseal osteochondromas with autosomal dominant inheritance and multiple parosteal bone proliferations
Familial cases of dysplasia epiphysealis hemimelica (DEH), or Trevor disease, are thought to represent dominant carpotarsal osteochondromatosis (DCO). Only three families affected by DCO have been reported so far in the literature. The authors report a fourth family: a 10-year-old girl, her father, and his cousin. Unlike the other reported cases of DCO this family had no carpal or upper limb epiphyseal osteochondromas and many of the other reported associations. The only consistent associated finding was the presence of multiple parosteal osteochondromatous proliferations. These cases may represent a variant of dominant carpotarsal osteochondromatosis or may represent a new entity.
Read the PubMed abstract

Skeletal Radiol ; 67-70 ; January 2008
Hutchinson-Gilford progeria syndrome: Combined treatment with statins and aminobisphosphonates extends longevity in mouse model
Several human progerias, including Hutchinson-Gilford progeria syndrome (HGPS), are caused by the accumulation at the nuclear envelope of farnesylated forms of truncated prelamin A, a protein that is also altered during normal aging. Previous studies in cells from individuals with HGPS have shown that farnesyltransferase inhibitors (FTIs) improve nuclear abnormalities associated with prelamin A accumulation, suggesting that these compounds could represent a therapeutic approach for this devastating progeroid syndrome. The authors show herein that both prelamin A and its truncated form progerin/LADelta50 undergo alternative prenylation by geranylgeranyltransferase in the setting of farnesyltransferase inhibition, which could explain the low efficiency of FTIs in ameliorating the phenotypes of progeroid mouse models. The authors also show that a combination of statins and aminobisphosphonates efficiently inhibits both farnesylation and geranylgeranylation of progerin and prelamin A and markedly improves the aging-like phenotypes of mice deficient in the metalloproteinase Zmpste24, including growth retardation, loss of weight, lipodystrophy, hair loss and bone defects.
Read the PubMed abstract

Nat Med ; 767-772 ; July 2008
Hutchinson-Gilford progeria syndrome: Effect of truncated prelamin A on keratinocytes, hair and skin
Hutchinson-Gilford progeria syndrome (HGPS) is an accelerated aging disorder caused by point mutation in LMNA encoding A-type nuclear lamins. The mutations in LMNA activate a cryptic splice donor site, resulting in expression of a truncated, prenylated prelamin A called progerin. Expression of progerin leads to alterations in nuclear morphology, which may underlie pathology in HGPS. The authors generated transgenic mice expressing progerin in epidermis under control of a keratin 14 promoter. The mice had severe abnormalities in morphology of skin keratinocyte nuclei, including nuclear envelope lobulation and decreased nuclear circularity not present in transgenic mice expressing wild-type human lamin A. Primary keratinocytes isolated from these mice had a higher frequency of nuclei with abnormal shape compared to those from transgenic mice expressing wild-type human lamin A. Treatment with a farnesyltransferase inhibitor significantly improved nuclear shape abnormalities and induced the formation of intranuclear foci in the primary keratinocytes expressing progerin.
Read the PubMed abstract

Hum Mol Genet ; 2357-2369 ; 1 August 2008
Niemann-Pick disease type B: A prospective, cross-sectional natural history survey
Fifty-nine patients who had Niemann-Pick disease type B participated in this multicenter, multinational, cross-sectional survey study. Medical histories; physical examinations; assessments of cardiorespiratory function, clinical laboratory data, and liver and spleen volumes; radiographic evaluation of the lungs and bone age; and quality-of-life assessments were obtained during a 2- to 3-day period. The results showed that 53% of the patients were male, 92% were white, and the median age was 17.6 years. The R608del mutation accounted for 25% of all disease alleles. Most patients initially presented with splenomegaly (78%) or hepatomegaly (73%). Frequent symptoms included bleeding (49%), pulmonary infections and shortness of breath (42% each), and joint/limb pain (39%). Growth was markedly delayed during adolescence. Patients commonly had low levels of platelets and high-density lipoprotein, elevated levels of low-density lipoprotein, very-low-density lipoprotein, triglycerides, leukocyte sphingomyelin, and serum chitotriosidase, and abnormal liver function test results. Nearly all patients had documented splenomegaly and hepatomegaly and interstitial lung disease.
Read the PubMed abstract

Pediatrics ; e341-e349 ; August 2008
Leber congenital amaurosis: Genes, proteins and disease mechanisms
Leber congenital amaurosis (LCA) is the most severe retinal dystrophy causing blindness or severe visual impairment before the age of 1 year. Linkage analysis, homozygosity mapping and candidate gene analysis facilitated the identification of 14 genes mutated in patients with LCA and juvenile retinal degeneration, which together explain approximately 70% of the cases. Several of these genes have also been implicated in other non-syndromic or syndromic retinal diseases, such as retinitis pigmentosa and Joubert syndrome, respectively. Despite a large degree of genetic and allelic heterogeneity, it is possible to identify the causative mutations in approximately 55% of LCA patients by employing a microarray-based, allele-specific primer extension analysis of all known DNA variants. The LCA genes encode proteins with a wide variety of retinal functions. Recently, several defects were identified that are likely to affect intra-photoreceptor ciliary transport processes. As the eye represents an accessible and immune-privileged organ, it appears to be uniquely suitable for human gene replacement therapy. Rodent, avian and canine models for LCA and profound visual impairment have been successfully corrected employing adeno-associated virus or lentivirus-based gene therapy. Moreover, phase 1 clinical trials have been carried out in humans with RPE65 deficiencies. Future LCA research will focus on the identification of the remaining causal genes, the elucidation of the molecular mechanisms of disease in the retina, and the development of gene therapy approaches for different genetic subtypes of LCA.
Read the PubMed abstract

Prog Retin Eye Res ; 391-419 ; July 2008
Legg-Calvé-Perthes disease and maternal smoking during pregnancy
The causes of Legg-Calvé-Perthes disease are largely unknown, but this paediatric disease seems to result from interruption of the blood supply to the proximal femur and is considered a vascular disease. Because maternal smoking during pregnancy influences foetal development and is associated with cardiovascular diseases in offspring, the authors hypothesized that this exposure is a risk for Legg-Calvé-Perthes disease and also investigated other markers of impaired foetal development and early-life exposures. The Swedish Inpatient Register identified 852 individuals with a diagnosis of Legg-Calvé-Perthes disease from 1983 to 2005, individually matched by year of birth, age, sex, and region of residence with 4432 randomly selected control subjects. Linkage with the Swedish Medical Birth Register provided information on prenatal factors, including maternal smoking. Maternal smoking during pregnancy was associated with an increased Legg-Calvé-Perthes disease risk, and heavy smoking was associated with a risk increase of almost 100%. Very low birth weight and cesarean section were independently associated with approximately 240% and 36% increases in the risk of Legg-Calvé-Perthes disease, respectively.
Read the PubMed abstract

Pediatrics ; e459-e464 ; August 2008
Stem Cells
(Rare) disease-specific induced pluripotent stem cells
Tissue culture of immortal cell strains from diseased patients is an invaluable resource for medical research but is largely limited to tumour cell lines or transformed derivatives of native tissues. Here the authors describe the generation of induced pluripotent stem (iPS) cells from patients with a variety of genetic diseases with either Mendelian or complex inheritance; including adenosine deaminase deficiency-related severe combined immunodeficiency, Shwachman-Bodian-Diamond syndrome, Gaucher disease type III, Duchenne and Becker muscular dystrophy, Parkinson disease, Huntington disease, juvenile-onset, type 1 diabetes mellitus, Down syndrome, and the carrier state of Lesch-Nyhan syndrome. Such disease-specific stem cells offer an unprecedented opportunity to recapitulate both normal and pathologic human tissue formation in vitro, thereby enabling disease investigation and drug development.
Read the PubMed abstract

Cell ; Epub ahead of print ; 6 August 2008
ALS: Induced pluripotent stem cells generated from patients can be differentiated into motor neurons
The generation of pluripotent stem cells from an individual patient would enable the large-scale production of the cell types affected by that patient's disease. These cells could in turn be used for disease modeling, drug discovery, and eventually autologous cell replacement therapies. Although recent studies have demonstrated the reprogramming of human fibroblasts to a pluripotent state, it remains unclear whether these induced pluripotent stem (iPS) cells can be produced directly from elderly patients with chronic disease. The authors generated iPS cells from an 82-year-old woman diagnosed with a familial form of amyotrophic lateral sclerosis (ALS). These patient-specific iPS cells possess properties of embryonic stem cells and were successfully directed to differentiate into motor neurons, the cell type destroyed in ALS.
Read the PubMed abstract

Science ; 1218-1221 ; 29 August 2008
Paediatric leukodystrophies: Stem cell-based treatment strategies for myelin disorders
The paediatric leukodystrophies comprise a category of disease manifested by neonatal or childhood deficiencies in myelin production or maintenance; these may be due to hereditary defects in one or more genes critical to the initiation of myelination, as in Pelizaeus-Merzbacher Disease, or to enzymatic deficiencies with aberrant substrate accumulation-related dysfunction, as in the lysosomal storage disorders. Despite differences in both phenotype and natural history, these disorders are all essentially manifested by a profound deterioration in neurological function with age. A congenital deficit in forebrain myelination is also noted in children with the periventricular leukomalacia of cerebral palsy, another major source of neurological morbidity. In light of the wide range of disorders to which congenital hypomyelination and/or postnatal demyelination may contribute, and the relative homogeneity of central oligodendrocytes and their progenitors, the paediatric leukodystrophies may be especially attractive targets for cell-based therapeutic strategies. As a result, glial progenitor cells (GPCs), which can give rise to new myelinogenic oligodendrocytes, have become of great interest as potential therapeutic vectors for the restoration of myelin to the hypomyelinated or dysmyelinated childhood CNS. In addition, by distributing themselves throughout the deficient host neuraxis after perinatal allograft, and giving rise to astrocytes as well as oligodendrocytes, glial progenitors appear to be of potential great utility in rectifying enzymatic deficiencies. In this review, the authors focus on current efforts to develop the use of isolated human GPCs as transplantable agents both for mediating enzymatic restoration to the enzyme-deficient brain and for therapeutic myelination in the disorders of congenital hypomyelination.
Read the PubMed abstract

Hum Mol Genet ; R76-83 ; 15 April 2008
Therapeutic Approaches
Phenylketonuria: Identification of pharmacological chaperones as potential therapeutic agents
Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in phenylalanine hydroxylase (PAH). Over 500 disease-causing mutations have been identified in humans, most of which result in PAH protein misfolding and increased turnover in vivo. The use of pharmacological chaperones to stabilize or promote correct folding of mutant proteins represents a promising new direction in the treatment of misfolding diseases. The authors performed a high-throughput ligand screen of over 1,000 pharmacological agents and identified 4 compounds (I-IV) that enhanced the thermal stability of PAH and did not show substantial inhibition of PAH activity. Furthermore, PAH activity in mouse liver increased after a 12-day oral administration of low doses of compounds III and IV.
Read the PubMed abstract

J Clin Invest ; 2858-2867 ; August 2008
Juvenile idiopathic arthritis: A randomised, double-blind, placebo-controlled withdrawal trial of abatacept
Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. The authors aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments. They conducted a double-blind, randomised controlled withdrawal trial with 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. Of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined criteria and were excluded. Of the patients who did respond to abatacept, 60 were randomly assigned to receive 10 mg/kg of abatacept at 28-day intervals for 6 months, or until a flare of the arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the treatment.
Read the PubMed abstract

Lancet ; 383-391 ; 2 August 2008
Sjögren syndrome: Inhibition through immunization with HSP60 and its peptide amino acids 437-460
Seven-week-old nonobese diabetic (NOD) mice were immunized with eukaryotic Hsp60 or an Hsp60-derived peptide. At 21 weeks of age, nondiabetic mice were investigated for salivary gland inflammation, exocrine function, and extraglandular disease manifestations. In addition, biomarker profiles were analyzed. In mice immunized with Hsp60 and aa 437-460, SS-related histopathologic features were significantly reduced compared with controls. In addition, 50% of Hsp60-injected mice and 33% of aa 437-460-injected mice retained normal exocrine function. Both treatments induced similar changes in biomarker profiles. Immunization with Hsp60 and its peptide aa 437-460 thus led to inhibition of SS in NOD mice.
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Arthritis Rheum ; 2318-2328 ; August 2008
Acromegaly: A critical analysis of clinically available somatostatin analog formulations
Short and long-acting somatostatin (SRIF) analogs are approved for clinical use in acromegaly. Recent analysis of the relative efficacy of octreotide LAR and lanreotide SR on the GH-IGF-I axis in acromegaly favored octreotide LAR in the secondary treatment of patients not preselected by SRIF responsiveness. A novel aqueous formulation of lanreotide, lanreotide Autogel (ATG), has recently been approved and is the predominant (and only in the United States) formulation of lanreotide used clinically. The authors performed a critical review of SRIF analog treatment to establish the relative efficacy of clinically available SRIF analog preparations in control of the GH-IGF-I axis in acromegaly. They found that Lanreotide ATG and octreotide LAR are equivalent in the control of symptoms and biochemical markers in patients with acromegaly.
Read the PubMed abstract

J Clin Endocrinol Metab ; 2957-2968 ; August 2008
Acromegaly: Preoperative octreotide treatment in patients with macroadenomas improves surgical cure rate
Surgery is the primary treatment for acromegaly. However, it often fails to cure the patient. New strategies that improve surgical outcome are needed. A study of 62 patients showed that six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.
Read the PubMed abstract

J Clin Endocrinol Metab ; 2984-2990 ; August 2008

Patient Management and Therapy
Meniere disease: 85% of patients are helped by medical treatment or lifestyle changes
Meniere disease is a chronic illness characterised by intermittent episodes of vertigo lasting from minutes to hours, with fluctuating sensorineural hearing loss, tinnitus, and aural pressure. Although there is currently no cure, more than 85% of patients are helped by either changes in lifestyle and medical treatment, or minimally invasive surgical procedures such as intratympanic steroid therapy, intratympanic gentamicin therapy, and endolymphatic sac surgery. Vestibular neurectomy has a very high rate of vertigo control and is available for patients with good hearing who have failed all other treatments. Labyrinthectomy is undertaken as a last resort and is best reserved for patients with unilateral disease and deafness.
Read the PubMed abstract

Lancet ; 406-416 ; 2 August 2008
Cystic fibrosis: Best practice guidelines for molecular genetic diagnosis - updated European recommendations
For the diagnosis of cystic fibrosis, the increasing number of laboratories offering molecular genetic analysis of the CFTR gene and the growing use of commercial kits strengthen the need for an update of previous best practice guidelines (published in 2000). The importance of organizing regional or national laboratory networks, to provide both primary and comprehensive CFTR mutation screening, is stressed. Current guidelines focus on strategies for dealing with increasingly complex situations of CFTR testing. Diagnostic flow charts now include testing in CFTR-related disorders and in foetal bowel anomalies. Emphasis is also placed on the need to consider ethnic or geographic origins of patients and individuals, on basic principles of risk calculation and on the importance of providing accurate laboratory reports. Finally, classification of CFTR mutations is reviewed, with regard to their relevance to pathogenicity and to genetic counselling.
Read the PubMed abstract

Eur J Hum Genet ; Epub ahead of print ; 6 August 2008

Orphan Drugs
FDA approves first bone marrow stimulator for chronic immune thrombocytopenic purpura
The U.S. Food and Drug Administration has approved Nplate (romiplostim), the first product that directly stimulates the bone marrow to produce platelets in patients with rare blood disorder chronic immune thrombocytopenic purpura. Nplate is manufactured by Amgen, Inc.

Partnersearch, Job Opportunities
EuroGentest: Call for participation
EuroGentest, the EC-funded network of excellence dedicated to promoting quality management of genetic laboratories and genetic services is recruiting accredited laboratories to participate in technique evaluation studies based on new technologies presented at their Satellite meeting at the ESHG meeting in Barcelona in June. Contact EuroGentest

EuroGentest also invites contributions to an inventory of (ongoing) validation studies performed within accredited diagnostic laboratories. Laboratories that would like to share their results and thus help prevent duplication of extensive validation on a specific test, method, kit or software tool are invited to Contact EuroGentest


What's on Where?
2nd Congress of Ring14 International Association for Rare Neurogenetic Diseases Research
Date: 25-27 September 2008
Venue: Reggio Emilia, Italy

An interesting and varied programme for professionals, patients and their families.
For further details

13th International Meeting of the World Muscle Society
Date: 29 September-2 October 2008
Venue: Newcastle upon Tyne, UK

New Insights into the pathogenesis of facioscapulohumeral muscular dystrophy, myotonic dystrophy and other dominant muscular dystrophies, Advances in the understanding and treatment of myasthenic disorders, Therapeutic advances in neuromuscular disorders, Advances across the neuromuscular field, including treatment and management.
For further details

European Research Conference in Paediatric Neurology
Date: 3-4 October 2008
Venue: Tubingen, Germany

The meeting enables researchers to meet colleagues in the same field in order to facilitate collaboration, and to foster the building of research networks. Most of the meeting is therefore reserved for discussion and interaction in the following working groups: Neurometabolic diseases, Autoimmune diseases, Neonatal Neurology, Neurodegeneration and Neuroprotection, Epilepsy, Neuromuscular Diseases, Genetics, Developmental Neurology, and Infection-related inflammatory CNS diseases.
For further details

Rare Diseases Warsaw 2008: MPS and Rare Diseases Conference
Date: 3-5 October 2008
Venue: Warsaw, Poland

The purpose of the conference is to introduce aspects of treatment and specialised medical care for rare genetic diseases and to strengthen cooperation and the exchange of experience between scientific environments and government institutions, as well as patient associations from Central and Eastern Europe.
For further details

International Conference on Thalassaemia and Haemoglobinopathies
Date: 8-11 October 2008
Venue: Singapore

The 11th International Conference on Thalassaemia and Haemoglobinopathies and the 13th International Thalassaemia TIF Conference for Thalassaemia Patients and Parents. "Equal Access to Quality Medical Care for Every Patient with Thalassaemia" is the theme of this year's conferences.
For further details

EuroGentest Workshop: Fulfilling the Requirements of ISO 15 189 - Management Review, IQC and EQA
Date: 9-10 October 2008
Venue: Berlin, Germany

This workshop will permit attendees to attain an in-depth understanding of what the ISO 15189 standard requires and how to translate these requirements into practical measures in the laboratory.
For further details

International Conference on Genetic and Molecular Basis of Rare Kidney Disorders
Date: 9-11 October 2008
Venue: Bergamo, Italy

This conference will bring together research geneticists, nephrologists, clinicians and experts from related specialties to discuss the latest findings on and around the core themes of rare kidney diseases. The speakers will cover a varieties of topics: glomerular filter structure and function in health and diseased states, genetic basis of glomerular diseases (focal and segmental glomerulosclerosis, hematuric syndromes, dense deposit disease), inherited disorders of tubular function, and renal developmental disorders. The Conference Keynote lecture will be delivered by Nobel Laureate professor Peter Agre, who will discuss the impact that the discovery of aquaporins has had on the understanding of physiologic and pathologic states.
For further details

6th World Rett Syndrome Congress
Date: 10-13 October 2008
Venue: Paris, France

Various aspects of Rett syndrome and MECP2 functioning, including fundamental, clinical and management topics.
For further details

11th Epilepsy & Society Conference
Date: 15-17 October 2008
Venue: Marseilles, France

The theme of the conference is "Active Life and Epilepsy" focusing on different aspects of achieving goals and a better quality of life. In addition to prominent medical experts in the field of epilepsy, speakers will include those working in epilepsy support and people with experience of epilepsy.
For further details

Tenth International Meeting on Osteogenesis Imperfecta
Date: 15-18 October 2008
Venue: Ghent, Belgium

Topics include: Bone homeostasis, murine models/collagen biology/biophysics, classification, genetics: genotype-phenotype, prenatal diagnosis/preimplantation diagnosis, biphosphonates, orthopedic management, hearing loss: physiopathology, surgery and imaging, other medical management issues, stomatology/dentistry, psychosocial aspects, new (therapeutic) perspectives.
For further details

EPPOSI 9th Workshop on Partnering for Rare Diseases Therapy Development
Date: 16-17 October 2008
Venue: Paris, France

Registration is open for the 2008 EPPOSI workshop, taking place at the National Assembly in Paris. The theme of the workshop is Orphan drugs: partnering along the chain and across the borders - Sharing strategies and tools for access to diagnosis and treatment.
For further details

Annual Meeting of the Italian Network for Promotion of Folic Acid and Prevention of Congenital Defects
Date: 17 October 2008
Venue: Rome, Italy

Current debate pivots on how to potentiate actions towards periconceptional supplementation, as well as on possible complementary strategies, such as nutritional education as well as generalised or facultative fortification. The principal issues discussed in this meeting relate to the risk-benefit analysis of prevention approaches using folic acid.
For further details

Dystonia Europe 2008
Date: 17-19 October 2008
Venue: Hamburg, Germany

This conference will provide a forum for discussion of the latest developments in clinical features, treatment and research of dystonia, with presentations from a broad range of leading experts from Europe and North America.
For further information

First Congress of the African Society for Immunodeficiencies
Date: 30 October-1 November 2008
Venue: Casablanca, Morocco

Organised by the African Society for Primary Immunodeficiencies in conjunction with the Moroccan Societies for Paediatrics and for Haematologies, themes to be explored during this congress include primary immunodeficiencies (PIDS) and the skin; PIDs and the lungs; PIDs and the adult patient; PIDS and lymphomas; PIDs and nutrition; and PIDs and vaccines.
For further information

ESF-UB Conference in Biomedicine: Biobanks
Date: 1-6 November 2008
Venue: Sant Feliu de Guixols, Spain

The ESF-UB Conference on Biobanks will be focused on providing an open forum of discussion on all aspects involved in the governance, management and use of human biobanks, technical solutions, ethical, legal, and social aspects, also providing participants with a broad overview of the existing models of biobanks and the international initiatives on population-based and disease-oriented biobanks. A limited number of grants are available for young researchers to cover the conference fee and possibly part of the travel costs.
For further information

Rare Tumors in Europe: Challenges and Solutions
Date: 6 November 2008
Venue: Brussels, Belgium

Details to follow shortly.
For further information

International Symposium on Rare Diseases: Inherited Neuromuscular Diseases: Translation from Pathomechanisms to Therapies
Date: 16-18 November 2008
Venue: Valencia, Spain

The symposium will permit exploration of the state-of–the-art of neuromuscular diseases as a whole, including muscular dystrophies, mitochondrial disorders, peripheral neuropathies, spinal muscular atrophy, motoneurone disease and Friedreich ataxia, and will explore pathogenic mechanisms and molecular targets for the different diseases, as a forum for discussion of the rational basis of the new therapeutic approaches.
For further information

From Cardiac Remodelling to Biotherapies: Homage to Ketty Schwartz
Date: 29 November 2008
Venue: Paris, France

The programme will include cardiac phenotype and remodelling in cardiopathies; genetics and pathophysiology of cardiac diseases; and therapies of cardiac and skeletal muscle diseases.
For further information

EuroGentest Workshop: Validation of Diagnostic Tests in Clinical Molecular Genetics
Date: 8-9 January 2009
Venue: Prague, Czech Republic

Genetic tests must be validated before diagnostic use to ensure that they perform according to the laboratory's requirements, and test validation is a formal requirement of many accreditation standards including ISO 15189. This workshop will examine the validation requirements of ISO 15189 and address practical ways of meeting them in the laboratory.
For further information

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 information

8th Balkan Meeting on Human Genetics
Date: 14-18 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 information

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 information


Press & Publications
If diseases that affect many people remain neglected, what about the rare conditions?
The 11 August issue of the BMJ contains an essay entitled, Orphan Diseases: Which Ones Do We Adopt? that presents the problem neglected disease sufferers face - even in developed countries - in accessing treatment. Neglected disease patients commonly share conditions of poverty and their diseases lead to ever-deepening impoverishment. Some rare disease sufferers, on the other hand - especially those in developed countries - have resources at their disposal enabling them to lobby for funds, research, recognition, and eventually treatments. Yet as the author points out, if neglected illnesses that impact millions of patients around the world continue to be ignored, how much harder is it for the rare diseases with their small populations to access resources and attract interest from both government and industry?
Two German-language rare disease articles consider epidemiological analysis and emphasise the importance of patient groups
A German-language review published in May two articles related to rare diseases. The first, Epidemiologic Challenges in Rare Diseases, considers the unique predicament rare diseases pose to the epidemiologist. Sample collection logistics, statistical methodology, random sampling and random errors all need to be rethought when studying the epidemiology of the rare disease. This article considers population sampling, surveillance methods, and capture techniques and reviews risk factor research challenges in relation to therapeutic or preventive trials. Consult the abstract

A second article, entitled Not Alone with a Rare Disease. The Importance of Self-Help Given by the Example of Anorectal Malformations reviews the usefulness of patient organisations not only for the rare disease patient and family but also for medical professionals and for insurance schemes. The article underscores the important role patient groups are playing in today’s interdisciplinary health care systems. Consult the 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, Lucile Abdennaji, Catherine Berens, Helen Dolk, Anders Fasth, Laura Fregonese, Edmund Jessop, Jordi Llinares-Garcia, Antoni Montserrat, Manuel Posada de la Paz, Ewa Pronicka, Claire Scharf-Kroener, Armelle Regnault, Janos Sandor, Domenica Taruscio, Paloma Tejada, T.O.F. Wagner
For more information on the Rare Diseases Task Force
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