Rare disease and orphan drugs journal最新文献

{"title":"Correction: A report and review of the recurrent c.811C > T variant and mutation spectrum of Kindler syndrome in East Asians: a diagnostic odyssey of 2 weeks versus 49 years","authors":"A. Chu, Joshua C. K. Chan, J. Fung, Wenshu Tang, Mianne Lee, Sze Man Wong, Man Ho Chung, Geoffrey Yu, V. Li, Calvin Tik Hei Ng, B. Chung","doi":"10.20517/rdodj.2023.28","DOIUrl":"https://doi.org/10.20517/rdodj.2023.28","url":null,"abstract":"","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cathepsin K: both a likely biomarker and a new therapeutic target in lymphangioleiomyomatosis?","authors":"S. Marchand-Adam, Marion Pronost, A. Saidi, F. Lecaille, G. Lalmanach","doi":"10.20517/rdodj.2022.24","DOIUrl":"https://doi.org/10.20517/rdodj.2022.24","url":null,"abstract":"Lymphangioleiomyomatosis (LAM) is a rare disease which is characterized by cystic lung destruction and lymphangiomas, and is associated with a high risk of osteoporosis-related bone fractures. Its diagnosis is based on pulmonary anatomopathological criteria combined with chest computed tomography. VEGF-D is the only serum diagnostic biomarker used in clinic, while inhibition of the mTOR pathway by rapamycin is currently the only reference therapy for LAM. Human cathepsin K (CatK), a potent collagenase predominantly found in osteoclasts, is considered as a valuable target for anti-osteoporosis and bone cancer therapy. Recently, CatK, which is overexpressed in lung cysts, was proposed as a putative LAM biomarker. Moreover, CatK may take part in the LAM pathophysiology by participating in pulmonary cystic destruction and bone degradation. Accordingly, targeting of collagenolytic activity of CatK by exosite-binding inhibitors in combination with mTOR inhibition could represent an innovative therapeutic option in reducing lung destruction in LAM.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A report and review of the recurrent c.811C>T variant and mutation spectrum of Kindler syndrome in East Asians: a diagnostic odyssey of 2 weeks versus 49 years","authors":"","doi":"10.20517/rdodj.2022.25","DOIUrl":"https://doi.org/10.20517/rdodj.2022.25","url":null,"abstract":"Kindler Syndrome (KS) is one of the rarest subtypes of epidermolysis bullosa (EB). It is characterised by congenital blistering, skin fragility, photosensitivity, and poikilodermatous skin changes. It is an autosomal recessive condition with an established disease-causing mechanism of having biallelic pathogenic variants in the FERMT1 gene. Multiple variants have been reported worldwide since the discovery in 1954. This case report describes two patients of Chinese descent with molecularly confirmed KS, one diagnosed in infancy while the other in mid-adulthood. It highlights the importance and clinical utility of diagnosing KS in children versus adults. The identification of recurrent c.811C>T variant in both patients also expedited the review of local databases and the existing mutation spectrum KS in East Asians.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Audiological findings in an Indian child with Johanson-Blizzard syndrome: a case report","authors":"Deena Priya, R. Bhat, G. Hinduja, S. S.","doi":"10.20517/rdodj.2022.07","DOIUrl":"https://doi.org/10.20517/rdodj.2022.07","url":null,"abstract":"Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disorder characterized by multi-system involvement and facial dysmorphic features. Sensorineural hearing loss is one of the most common manifestations of this pathology. Detailed audiological evaluation in confirmed cases of JBS is essential for the appropriate management of hearing loss. We present the audiological features of a six-year-old Indian girl with Johanson-Blizzard syndrome along with the less emphasized association of café-au-lait spots with JBS.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The discovery of the Papillon-Lefèvre syndrome, a rare cathepsin C related lysosomal disease","authors":"B. Korkmaz, Seda Seren, E. Kara, C. Moss","doi":"10.20517/rdodj.2022.26","DOIUrl":"https://doi.org/10.20517/rdodj.2022.26","url":null,"abstract":"","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Different E-box binding transcription factors, similar neuro-developmental defects: ZEB2 (Mowat-Wilson syndrome) and TCF4 (Pitt-Hopkins syndrome)","authors":"Lize Meert, Judith C. Birkhoff, A. Conidi, R. Poot, D. Huylebroeck","doi":"10.20517/rdodj.2022.03","DOIUrl":"https://doi.org/10.20517/rdodj.2022.03","url":null,"abstract":"ZEB2 and TCF4 are transcription factors (TFs) whose locations in embryos overlap in many sites and developmental phases, including in the forebrain and its cortical neurons. De novo mutations cause the phenotypically overlapping, haploinsufficient Mowat-Wilson (MOWS, in the ZEB2 gene) and Pitt-Hopkins (PTHS, in TCF4) syndromes, which currently cannot be cured. Mutant alleles have been mapped and defects documented (also in brain function) in MOWS and PTHS patients. Appropriately designed mouse models and cells derived from these, as well as cellular models including cultured pluripotent cells, enable investigating the genetic and molecular mechanisms underlying the developmental deficiencies that manifest after birth in the nervous systems and their multiple cell types, as well as those of organs other than the brain, in MOWS and PTHS. Biochemical analyses of cell type-specific transcriptomic changes in these perturbation models as compared to control cells, the identification of the intact-factor dependent and direct target genes, and of partner proteins including chromatin modulators, are revealing complex and multiple modes of action that eventually will explain target gene selectivity for these TFs. Both TFs have also been found to operate in acute and chronic diseases and cell-based repair processes after tissue or organ injury. In addition, the defective function also arises from their aberrant gene expression, which will require a deeper investigation of how the transcription of these TF genes is regulated. Furthermore, these two factors genetically and biochemically interact. This review combines the essentials and recent progress for both TFs for the first time, with a focus on MOWS and PTHS.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"30 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The importance of psychological support for parents and caregivers of children with a rare disease at diagnosis","authors":"T. Kenny, Kathleen R. Bogart, A. Freedman, Claire Garthwaite, S. Henley, M. Bolz-Johnson, S. Mohammed, Jill Walton, Kym Winter, Deborah Woodman","doi":"10.20517/rdodj.2022.04","DOIUrl":"https://doi.org/10.20517/rdodj.2022.04","url":null,"abstract":"Rare diseases are complex and difficult to diagnose, with parents and caregivers often reporting significant delays in receiving a definitive diagnosis. Following diagnosis, parents and caregivers often feel overwhelmed with emotions, including relief, guilt, and shock. The culmination of this emotional burden may lead to a deterioration of psychological health, ultimately reaching a stage where the parents struggle to cope. A systematic literature review was conducted of the articles on this topic by searching the electronic database, PubMed. Further studies were retrieved from a reference listing of relevant articles and consultation with experts in the field. The review was based on the guidance in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol. The initial search identified 1276 articles, of which 37 met the inclusion criteria and were included in this review. The literature revealed key factors that appeared to contribute to psychological stress, including prolonged diagnostic odyssey, poor diagnostic delivery, lack of information and specialist knowledge, and convoluted healthcare systems. This review reinforces the need for psychological support amongst parents and caregivers of children with a rare disease at the time of diagnosis. The results of this literature review will be used to develop a statement of good practice for the support of parents and caregivers when a rare disease diagnosis is given.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Burden of cerebral adrenoleukodystrophy on affected children and their families through the eyes of family caregivers","authors":"C. Sevin, Gaelle Thomas, Elise Saunier Vivar, E. Yazbeck, Hélène Rochereuil, F. Bignami, A. Clément, Marieke Podevin","doi":"10.20517/rdodj.2022.13","DOIUrl":"https://doi.org/10.20517/rdodj.2022.13","url":null,"abstract":"Aim: This research assessed the needs of family caregivers of children with cerebral adrenoleukodystrophy (cALD), focusing on the diagnostic process; the burden of the disease on the child and their caregiver’s quality of life; and the physical, social, psychological, professional, and financial impacts on the whole family. Methods: Family caregivers of children with cALD were recruited via the European Leukodystrophies Association International’s online platform, Leuconnect, to respond to a quantitative survey and a quality-of-life questionnaire and participate in a qualitative semi-structured interview. The questions focused on disease experience from onset to diagnosis and consequences on current life. Twelve family caregivers of 14 children were interviewed. Results: cALD diagnosis took an average of 16.5 months, and 8 of 12 children were misdiagnosed, with parents often describing a lack of listening from doctors. Caregivers described bedridden children whose poor quality of life correlated with a high Neurologic Function Score. On average, they needed to care for their children 7.7 h/day, with serious consequences for their employment, social life, and psychological state. Conclusion: Our interviews with family caregivers helped us to consider limiting diagnostic wandering by improving the skills of general practitioners and public knowledge of pathology. By gathering information on precise daily routines centered around a dependent child, we can better understand how to effectively support families by adapting not only the global care of the child but also to the following needs expressed for the entire family: better information, coordination of both care and administrative procedures, and real respite.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysosomal storage disorders with neurological manifestations","authors":"Vikas Munjal, Maria Clarke, Joshua Vignolles-Jeong, Jasmine A. Valencia, Meika Travis, L. Samaranch","doi":"10.20517/rdodj.2021.05","DOIUrl":"https://doi.org/10.20517/rdodj.2021.05","url":null,"abstract":"Lysosomal storage disorders (LSDs) constitute a large group of rare, multisystemic, progressive, inherited disorders of metabolism. The aberrant metabolic processes often lead to the cellular accumulation of incompletely metabolized macromolecules or their metabolic byproducts. Most of the patients affected by LSD can experience a variety of neurological presentations including, but not limited to, psychiatric complications, seizures, and/or developmental delays. The onset of symptoms can range from birth to adulthood, and disease severity can vary. Since there is significant overlap in the symptomatology of LSDs, diagnosis is typically confirmed through biochemical and molecular assays. There are currently no approved cures for any LSDs; however, in most cases, treatment of symptoms can lead to better outcomes and improvements in quality of life. The use of hematopoietic stem cell transplantation, enzyme replacement or substrate reduction therapy, and viral vector gene transfer is the subject of many ongoing and completed clinical trials. In this mini review, we provide an overview of LSDs with neurological manifestations, describe the current endeavors in alleviating peripheral symptoms and discuss effective therapeutics strategies.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing the value of clinical networks for rare diseases","authors":"M. Bolz-Johnson, Louise Clément, W. Gahl, Carmencita Padilla, Yukiko Nishumura, Rachel Yang, Lisa Sarfaty, N. Hoogerbrugge, G. Baynam, T. Kenny","doi":"10.20517/rdodj.2022.01","DOIUrl":"https://doi.org/10.20517/rdodj.2022.01","url":null,"abstract":"Healthcare networks for rare diseases are developing around the world, concentrating expertise and knowledge from China and Japan to the United States and across Europe. Networked care is scaling up as an effective model of care for rare diseases, with prevention, diagnosis, care and treatment administered locally, informed by the body of knowledge and expertise from the whole network. Now, as the United Nations encourages the development of rare disease networks in all countries, it is timely to reflect on the key characteristics of an effective network. This article aims to identify the core themes needed for a clinical network to be healthy. This article drawing on experience from existing networks through a series of semi-structured interviews, insights from leaders of existing networks are then triangulated with the published evidence. The review aims to identify the themes that allow a clinical network to be effective and flourish. Healthcare networks are best understood as learning systems to generate collaborative knowledge used to inform the best possible care. Six themes are consistently reported in the literature and leaders’ experience: Trust, Communication, Leadership, Learning, Diversity and Resources. Learning together is a key element of the success of effective networks and is most effective when networks are professionally multi-cultural and diverse, including the voices of people living with a rare disease. Patient representative involvement is fundamental to network collaboration and is recognized as a key aspect of early successes. Clinical leadership is critical to providing legitimacy and trust, creating a common identity and promoting collaboration. Networks take time, resources and coordination to develop. Although in-kind support and voluntary contributions of network members are important, inadequate resourcing is a critical barrier to the long-term sustainability and effectiveness of networks. This review explores the core themes of effective networks. Through harnessing digital solutions that enable experts to coordinate care virtually across a clinical network, healthcare for people living with a rare disease is evolving to meet their complex needs. However, payment models to finance these models of care still lag behind innovative healthcare delivery models.","PeriodicalId":74638,"journal":{"name":"Rare disease and orphan drugs journal","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67659401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}