Pub Date : 2024-07-24DOI: 10.1186/s13023-024-03280-0
Julia Gresky, Melina Frotscher, Juliane Dorn, Kristina Scheelen-Nováček, Yannick Ahlbrecht, Tina Jakob, Toni Schönbuchner, José Canalejo, Benjamin Ducke, Emmanuele Petiti
Background: The history of rare diseases is largely unknown. Research on this topic has focused on individual cases of prominent (historical) individuals and artistic (e.g., iconographic) representations. Medical collections include large numbers of specimens that exhibit signs of rare diseases, but most of them date to relatively recent periods. However, cases of rare diseases detected in mummies and skeletal remains derived from archaeological excavations have also been recorded. Nevertheless, this direct evidence from historical and archaeological contexts is mainly absent from academic discourse and generally not consulted in medical research on rare diseases.
Results: This desideratum is addressed by the Digital Atlas of Ancient Rare Diseases (DAARD: https://daard.dainst.org ), which is an open access/open data database and web-based mapping tool that collects evidence of different rare diseases found in skeletons and mummies globally and throughout all historic and prehistoric time periods. This easily searchable database allows queries by diagnosis, the preservation level of human remains, research methodology, place of curation and publications. In this manuscript, the design and functionality of the DAARD are illustrated using examples of achondroplasia and other types of stunted growth.
Conclusions: As an open, collaborative repository for collecting, mapping and querying well-structured medical data on individuals from ancient times, the DAARD opens new avenues of research. Over time, the number of rare diseases will increase through the addition of new cases from varied backgrounds such as museum collections and archaeological excavations. Depending on the research question, phenotypic or genetic information can be retrieved, as well as information on the general occurrence of a rare disease in selected space-time intervals. Furthermore, for individuals diagnosed with a rare disease, this approach can help them to build identity and reveal an aspect of their condition they might not have been aware of. Thus, the DAARD contributes to the understanding of rare diseases from a long-term perspective and adds to the latest medical research.
{"title":"The Digital Atlas of Ancient Rare Diseases (DAARD) and its relevance for current research.","authors":"Julia Gresky, Melina Frotscher, Juliane Dorn, Kristina Scheelen-Nováček, Yannick Ahlbrecht, Tina Jakob, Toni Schönbuchner, José Canalejo, Benjamin Ducke, Emmanuele Petiti","doi":"10.1186/s13023-024-03280-0","DOIUrl":"10.1186/s13023-024-03280-0","url":null,"abstract":"<p><strong>Background: </strong>The history of rare diseases is largely unknown. Research on this topic has focused on individual cases of prominent (historical) individuals and artistic (e.g., iconographic) representations. Medical collections include large numbers of specimens that exhibit signs of rare diseases, but most of them date to relatively recent periods. However, cases of rare diseases detected in mummies and skeletal remains derived from archaeological excavations have also been recorded. Nevertheless, this direct evidence from historical and archaeological contexts is mainly absent from academic discourse and generally not consulted in medical research on rare diseases.</p><p><strong>Results: </strong>This desideratum is addressed by the Digital Atlas of Ancient Rare Diseases (DAARD: https://daard.dainst.org ), which is an open access/open data database and web-based mapping tool that collects evidence of different rare diseases found in skeletons and mummies globally and throughout all historic and prehistoric time periods. This easily searchable database allows queries by diagnosis, the preservation level of human remains, research methodology, place of curation and publications. In this manuscript, the design and functionality of the DAARD are illustrated using examples of achondroplasia and other types of stunted growth.</p><p><strong>Conclusions: </strong>As an open, collaborative repository for collecting, mapping and querying well-structured medical data on individuals from ancient times, the DAARD opens new avenues of research. Over time, the number of rare diseases will increase through the addition of new cases from varied backgrounds such as museum collections and archaeological excavations. Depending on the research question, phenotypic or genetic information can be retrieved, as well as information on the general occurrence of a rare disease in selected space-time intervals. Furthermore, for individuals diagnosed with a rare disease, this approach can help them to build identity and reveal an aspect of their condition they might not have been aware of. Thus, the DAARD contributes to the understanding of rare diseases from a long-term perspective and adds to the latest medical research.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11267669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-23DOI: 10.1186/s13023-024-03200-2
Valentina Trevisan, Eugenio De Corso, Germana Viscogliosi, Roberta Onesimo, Alessandro Cina, Marco Panfili, Lucrezia Perri, Cristiana Agazzi, Valentina Giorgio, Donato Rigante, Giovanni Vento, Patrizia Papacci, Filomena Valentina Paradiso, Sara Silvaroli, Lorenzo Nanni, Nicoletta Resta, Marco Castori, Jacopo Galli, Gaetano Paludetti, Giuseppe Zampino, Chiara Leoni
Background: Lymphatic malformations are vascular developmental anomalies varying from local superficial masses to diffuse infiltrating lesions, resulting in disfigurement. Patients' outcomes range from spontaneous regression to severe sequelae notwithstanding appropriate treatment. The current classification guides, in part, clinicians through the decision-making process, prognosis prediction and choice of therapeutic strategies. Even though the understanding of molecular basis of the disease has been recently improved, a standardized management algorithm has not been reached yet.
Results: Here, we report our experience on five children with different lymphatic anomalies of the head and neck region treated by applying a multidisciplinary approach reaching a consensus among specialists on problem-solving and setting priorities.
Conclusions: Although restitutio ad integrum was rarely achieved and the burden of care is challenging for patients, caregivers and healthcare providers, this study demonstrates how the referral to expert centres can significantly improve outcomes by alleviating parental stress and ameliorating patients' quality of life. A flow-chart is proposed to guide the multidisciplinary care of children with LMs and to encourage multidisciplinary collaborative initiatives to implement dedicated patients' pathways.
{"title":"A multi-step approach to overcome challenges in the management of head and neck lymphatic malformations, and response to treatment.","authors":"Valentina Trevisan, Eugenio De Corso, Germana Viscogliosi, Roberta Onesimo, Alessandro Cina, Marco Panfili, Lucrezia Perri, Cristiana Agazzi, Valentina Giorgio, Donato Rigante, Giovanni Vento, Patrizia Papacci, Filomena Valentina Paradiso, Sara Silvaroli, Lorenzo Nanni, Nicoletta Resta, Marco Castori, Jacopo Galli, Gaetano Paludetti, Giuseppe Zampino, Chiara Leoni","doi":"10.1186/s13023-024-03200-2","DOIUrl":"10.1186/s13023-024-03200-2","url":null,"abstract":"<p><strong>Background: </strong>Lymphatic malformations are vascular developmental anomalies varying from local superficial masses to diffuse infiltrating lesions, resulting in disfigurement. Patients' outcomes range from spontaneous regression to severe sequelae notwithstanding appropriate treatment. The current classification guides, in part, clinicians through the decision-making process, prognosis prediction and choice of therapeutic strategies. Even though the understanding of molecular basis of the disease has been recently improved, a standardized management algorithm has not been reached yet.</p><p><strong>Results: </strong>Here, we report our experience on five children with different lymphatic anomalies of the head and neck region treated by applying a multidisciplinary approach reaching a consensus among specialists on problem-solving and setting priorities.</p><p><strong>Conclusions: </strong>Although restitutio ad integrum was rarely achieved and the burden of care is challenging for patients, caregivers and healthcare providers, this study demonstrates how the referral to expert centres can significantly improve outcomes by alleviating parental stress and ameliorating patients' quality of life. A flow-chart is proposed to guide the multidisciplinary care of children with LMs and to encourage multidisciplinary collaborative initiatives to implement dedicated patients' pathways.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11265367/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1186/s13023-024-03253-3
Johnny Kenth, Elizabeth Maughan, Colin R Butler, Jasleen Gabrie, Maral Rouhani, Benjamin Silver, Olumide K Ogunbiyi, Stuart Wilkinson, Reema Nandi, Robert Walker, Nagarajan Muthialu, Simon Jones, Richard Hewitt, Iain A Bruce
Mucopolysaccharidosis (MPS) type IVA is a rare lysosomal storage disorder caused by aberrations of the N-acetyl-galactosamine-6-sulfatase (GALNS) enzyme. MPS IVA is associated with a wide gamut of respiratory and airway disorders that manifest in a continuum of severity. In individuals exhibiting severe phenotypic expression, terminal stages of the disease frequently culminate in life-threatening, critical airway obstruction. These manifestations of end-stage disease are engendered by an insidious progression of multi-level airway pathologies, comprising of tracheomalacia, stenosis, tortuosity and 'buckling'. Historically, the management of end-stage airway disease has predominantly leaned towards palliative modalities. However, contemporary literature has posited that the potential benefits of tracheal resection with aortopexy, performed under cardiopulmonary bypass (CPB), may offer a promising therapeutic option. In this context, we report on outcomes from patients undergoing a novel approach to tracheal resection that is combined with manubrial resection, leading to improved airway calibre, obviating the requisition for CPB. In this study, seven patients with severe MPS IVA exhibited clinical symptoms and radiological evidence indicative of advanced airway obstruction. All patients had a tracheal resection with a partial upper manubriectomy via transcervical approach, which did not require CPB. The surgical cohort consisted of 5 females and 2 males, the median age was 16 years (range 11-19) and the median height was 105.6cm (range 96.4-113.4). Postoperatively, significant improvements were seen in forced expiratory volume in 1 second (FEV1), with a mean increase of 0.68 litres (95% CI: 0.45-0.91; SD: 0.20). Notably, other spirometry variables also showed meaningful improvements, providing evidence of positive treatment effects. Furthermore, there were no major long-term complications, and the procedure resulted in a significant enhancement in patient-reported domains using PedsQL (version 4.0). This study represents the largest case series to date, on tracheal resection in patients with severe MPS IVA. Our findings demonstrate the effectiveness of the transcervical approach with partial manubriectomy for improving respiratory function and quality of life for individuals with advanced airway obstruction. Tracheal resection presents a promising treatment modality for severe cases of MPS IVA. Successful outcomes rely on meticulous multidisciplinary assessment, judicious decision-making, and appropriate timing of tracheal surgery. Further research and long-term follow-up studies are warranted to validate the long-term efficacy and safety of this approach.
{"title":"Novel approach for tracheal resection in Morquio a syndrome with end-stage critical airway obstruction: a UK case series","authors":"Johnny Kenth, Elizabeth Maughan, Colin R Butler, Jasleen Gabrie, Maral Rouhani, Benjamin Silver, Olumide K Ogunbiyi, Stuart Wilkinson, Reema Nandi, Robert Walker, Nagarajan Muthialu, Simon Jones, Richard Hewitt, Iain A Bruce","doi":"10.1186/s13023-024-03253-3","DOIUrl":"https://doi.org/10.1186/s13023-024-03253-3","url":null,"abstract":"Mucopolysaccharidosis (MPS) type IVA is a rare lysosomal storage disorder caused by aberrations of the N-acetyl-galactosamine-6-sulfatase (GALNS) enzyme. MPS IVA is associated with a wide gamut of respiratory and airway disorders that manifest in a continuum of severity. In individuals exhibiting severe phenotypic expression, terminal stages of the disease frequently culminate in life-threatening, critical airway obstruction. These manifestations of end-stage disease are engendered by an insidious progression of multi-level airway pathologies, comprising of tracheomalacia, stenosis, tortuosity and 'buckling'. Historically, the management of end-stage airway disease has predominantly leaned towards palliative modalities. However, contemporary literature has posited that the potential benefits of tracheal resection with aortopexy, performed under cardiopulmonary bypass (CPB), may offer a promising therapeutic option. In this context, we report on outcomes from patients undergoing a novel approach to tracheal resection that is combined with manubrial resection, leading to improved airway calibre, obviating the requisition for CPB. In this study, seven patients with severe MPS IVA exhibited clinical symptoms and radiological evidence indicative of advanced airway obstruction. All patients had a tracheal resection with a partial upper manubriectomy via transcervical approach, which did not require CPB. The surgical cohort consisted of 5 females and 2 males, the median age was 16 years (range 11-19) and the median height was 105.6cm (range 96.4-113.4). Postoperatively, significant improvements were seen in forced expiratory volume in 1 second (FEV1), with a mean increase of 0.68 litres (95% CI: 0.45-0.91; SD: 0.20). Notably, other spirometry variables also showed meaningful improvements, providing evidence of positive treatment effects. Furthermore, there were no major long-term complications, and the procedure resulted in a significant enhancement in patient-reported domains using PedsQL (version 4.0). This study represents the largest case series to date, on tracheal resection in patients with severe MPS IVA. Our findings demonstrate the effectiveness of the transcervical approach with partial manubriectomy for improving respiratory function and quality of life for individuals with advanced airway obstruction. Tracheal resection presents a promising treatment modality for severe cases of MPS IVA. Successful outcomes rely on meticulous multidisciplinary assessment, judicious decision-making, and appropriate timing of tracheal surgery. Further research and long-term follow-up studies are warranted to validate the long-term efficacy and safety of this approach.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141739433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-22DOI: 10.1186/s13023-024-03286-8
Thomas Frederick Dunne, Daniel Jeffries, Lucy Mckay
An estimated 3.5 million people in the UK live with a rare disease however due to the rarity of each individual condition this is not currently reflected in mainstream medical education. As a result, common features of living with a rare condition include diagnostic delay, poor coordination of health and social care and lack of access to specialist care and treatment. This is well documented in reports published by patient advocacy groups collating the patient experience and has been highlighted by the Department of Health and Social Care in its UK Rare Diseases Framework. One of the four priority areas outlined in this policy published in 2021 is ‘increasing awareness amongst healthcare professionals’. Medics4RareDiseases (M4RD), a charity based in the UK, has proposed a disease-agnostic approach to educating doctors about rare disease, focusing on the common challenges experienced across this heterogeneous collection of conditions, rather than on the minutiae of each of the > 7000 rare conditions. A literature search using MEDLINE, PubMed Central and Bookshelf confirmed a lack of broad rare disease teaching in medical literature; none of the 10 final resources identified focused on the topic as a whole. To address this, M4RD created the course ‘Rare Disease 101’. It is accessed online using a learning management system that is free, contains interactive lessons, hosts a discussion board and is easily updated. In the 29 months since going live, 942 individuals have registered with 204 having completed the course; early feedback from 33 respondents was unanimously positive (all participants rated at least good (76%: excellent)) demonstrating that both clinicians and patients can benefit from broad rare disease education. The course is freely available to all at https://learn.m4rd.org/ . Disease-agnostic training about rare disease as a large patient population, focusing on its unique profile of unmet needs, is required. Rare Disease 101 provides a pragmatic approach to an educational challenge that leads to poor patient outcomes. Early results suggest that the educational programme is well-received but further evaluation and assessment is needed.
{"title":"Rare disease 101: an online resource teaching on over 7000 rare diseases in one short course","authors":"Thomas Frederick Dunne, Daniel Jeffries, Lucy Mckay","doi":"10.1186/s13023-024-03286-8","DOIUrl":"https://doi.org/10.1186/s13023-024-03286-8","url":null,"abstract":"An estimated 3.5 million people in the UK live with a rare disease however due to the rarity of each individual condition this is not currently reflected in mainstream medical education. As a result, common features of living with a rare condition include diagnostic delay, poor coordination of health and social care and lack of access to specialist care and treatment. This is well documented in reports published by patient advocacy groups collating the patient experience and has been highlighted by the Department of Health and Social Care in its UK Rare Diseases Framework. One of the four priority areas outlined in this policy published in 2021 is ‘increasing awareness amongst healthcare professionals’. Medics4RareDiseases (M4RD), a charity based in the UK, has proposed a disease-agnostic approach to educating doctors about rare disease, focusing on the common challenges experienced across this heterogeneous collection of conditions, rather than on the minutiae of each of the > 7000 rare conditions. A literature search using MEDLINE, PubMed Central and Bookshelf confirmed a lack of broad rare disease teaching in medical literature; none of the 10 final resources identified focused on the topic as a whole. To address this, M4RD created the course ‘Rare Disease 101’. It is accessed online using a learning management system that is free, contains interactive lessons, hosts a discussion board and is easily updated. In the 29 months since going live, 942 individuals have registered with 204 having completed the course; early feedback from 33 respondents was unanimously positive (all participants rated at least good (76%: excellent)) demonstrating that both clinicians and patients can benefit from broad rare disease education. The course is freely available to all at https://learn.m4rd.org/ . Disease-agnostic training about rare disease as a large patient population, focusing on its unique profile of unmet needs, is required. Rare Disease 101 provides a pragmatic approach to an educational challenge that leads to poor patient outcomes. Early results suggest that the educational programme is well-received but further evaluation and assessment is needed.","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141739432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-20DOI: 10.1186/s13023-024-03281-z
Fábio Fernandes, Georgina Del Cisne Jadán Luzuriaga, Guilherme Wesley Peixoto da Fonseca, Edileide Barros Correia, Alzira Alves Siqueira Carvalho, Ariane Vieira Scarlatelli Macedo, Otavio Rizzi Coelho-Filho, Phillip Scheinberg, Murillo Oliveira Antunes, Pedro Vellosa Schwartzmann, Sandrigo Mangini, Wilson Marques, Marcus Vinicius Simões
Background: Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. We present data on physical signs and symptoms, cardiac and neurological assessments and genetic profile of patients enrolled in the Transthyretin Cardiac Amyloidosis Registry of the State of São Paulo, Brazil.
Results: Six hundred-forty-four patients were enrolled, 505 with the variant form (ATTRv) and 139 with wild-type (ATTRwt). Eleven different mutations were detected, the most common being Val50Met (47.5%) and V142Ile (39.2%). Overall, more than half of the patients presented cardiac involvement, and the difference in this proportion between the ATTRv and ATTRwt groups was significant (43.9 vs. 89.9%; p < 0.001). The prevalence of the neurological phenotype also differed between ATTRv and ATTRwt (56.8 vs. 31.7%; p < 0.001). The mixed phenotype was found in 25.6% of the population, without a significant difference between ATTRv and ATTRwt groups. A group of patients remained asymptomatic (10.4%), with a lower proportion of asymptomatic ATTRwt patients.
Conclusions: This study details the clinical and genetic spectrum of patients with ATTR in São Paulo, Brazil. This preliminary analysis highlights the considerable phenotypic heterogeneity of neurological and cardiac manifestations in patients with variant and wild-type ATTR.
{"title":"Clinical and genetic profiles of patients with hereditary and wild-type transthyretin amyloidosis: the Transthyretin Cardiac Amyloidosis Registry in the state of São Paulo, Brazil (REACT-SP).","authors":"Fábio Fernandes, Georgina Del Cisne Jadán Luzuriaga, Guilherme Wesley Peixoto da Fonseca, Edileide Barros Correia, Alzira Alves Siqueira Carvalho, Ariane Vieira Scarlatelli Macedo, Otavio Rizzi Coelho-Filho, Phillip Scheinberg, Murillo Oliveira Antunes, Pedro Vellosa Schwartzmann, Sandrigo Mangini, Wilson Marques, Marcus Vinicius Simões","doi":"10.1186/s13023-024-03281-z","DOIUrl":"10.1186/s13023-024-03281-z","url":null,"abstract":"<p><strong>Background: </strong>Transthyretin amyloidosis (ATTR) is a multisystem disease caused by the deposition of fibrillar protein in organs and tissues. ATTR genotypes and phenotypes are highly heterogeneous. We present data on physical signs and symptoms, cardiac and neurological assessments and genetic profile of patients enrolled in the Transthyretin Cardiac Amyloidosis Registry of the State of São Paulo, Brazil.</p><p><strong>Results: </strong>Six hundred-forty-four patients were enrolled, 505 with the variant form (ATTRv) and 139 with wild-type (ATTRwt). Eleven different mutations were detected, the most common being Val50Met (47.5%) and V142Ile (39.2%). Overall, more than half of the patients presented cardiac involvement, and the difference in this proportion between the ATTRv and ATTRwt groups was significant (43.9 vs. 89.9%; p < 0.001). The prevalence of the neurological phenotype also differed between ATTRv and ATTRwt (56.8 vs. 31.7%; p < 0.001). The mixed phenotype was found in 25.6% of the population, without a significant difference between ATTRv and ATTRwt groups. A group of patients remained asymptomatic (10.4%), with a lower proportion of asymptomatic ATTRwt patients.</p><p><strong>Conclusions: </strong>This study details the clinical and genetic spectrum of patients with ATTR in São Paulo, Brazil. This preliminary analysis highlights the considerable phenotypic heterogeneity of neurological and cardiac manifestations in patients with variant and wild-type ATTR.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264909/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141734768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-19DOI: 10.1186/s13023-024-03269-9
Raymond Dalgleish, Dimitra Micha, Andrea Superti-Furga, Fleur S van Dijk, David O Sillence
A paper published in Orphanet Journal of Rare Diseases proposes a new classification of osteogenesis imperfecta (OI) based upon underlying pathological mechanisms. The proposed numbering of OI types conflicts with the currently used numbering and is likely to lead to confusion. In addition, classification of OI according to underlying pathogenic mechanisms is not novel.
发表在《罕见病杂志》(Orphanet Journal of Rare Diseases)上的一篇论文提出了一种基于潜在病理机制的成骨不全症(OI)新分类。拟议的成骨不全症类型编号与目前使用的编号相冲突,很可能导致混淆。此外,根据潜在的致病机制对成骨不全症进行分类并不新颖。
{"title":"Letter to the editor: Re: Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification.","authors":"Raymond Dalgleish, Dimitra Micha, Andrea Superti-Furga, Fleur S van Dijk, David O Sillence","doi":"10.1186/s13023-024-03269-9","DOIUrl":"10.1186/s13023-024-03269-9","url":null,"abstract":"<p><p>A paper published in Orphanet Journal of Rare Diseases proposes a new classification of osteogenesis imperfecta (OI) based upon underlying pathological mechanisms. The proposed numbering of OI types conflicts with the currently used numbering and is likely to lead to confusion. In addition, classification of OI according to underlying pathogenic mechanisms is not novel.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11264877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141727515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.1186/s13023-024-03283-x
Justyna Spychalska, Magdalena Duńska, Anna Myślińska, Monika Majewska-Wierzbicka, Edyta Klimczak-Jajor, Eliza Głodkowska-Mrówka
Background: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by PIG-A mutations, leading to glycophosphatidylinositol (GPI)-anchored proteins deficiency that triggers hemolysis - a hallmark of the disease. PNH diagnostics is based on high-sensitivity multicolor flow cytometry (MFC), enabling to detect even small populations of PNH cells. In this single-center, retrospective study, we aimed to characterize a cohort of PNH clone-positive patients first time screened from January 1st, 2013 until December 31st, 2022 with MFC according to International Clinical Cytometry Society PNH Consensus Guidelines.
Results: Out of 2790 first-time screened individuals, the presence of PNH clone in neutrophils was detected in 322 patients, including 49 children and 273 adults. Annual incidence was stable at a median of 31 patients (14 and 19 with clone sizes ≤ 1% and > 1%, respectively), with a decline in number of patients with clone sizes > 1% observed in 2020, potentially influenced by the COVID-19 pandemic. The most common screening indications were aplastic anemia and other cytopenias.
Conclusions: A significant underrepresentation of hemolytic patients was observed as compared to the published cohorts suggesting that these patients are missed in diagnostic process and classic PNH remains underdiagnosed in Poland.
{"title":"Diagnostic landscape of first-time cytometric screening for paroxysmal nocturnal hemoglobinuria in Poland in 2013-2022.","authors":"Justyna Spychalska, Magdalena Duńska, Anna Myślińska, Monika Majewska-Wierzbicka, Edyta Klimczak-Jajor, Eliza Głodkowska-Mrówka","doi":"10.1186/s13023-024-03283-x","DOIUrl":"10.1186/s13023-024-03283-x","url":null,"abstract":"<p><strong>Background: </strong>Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell disorder characterized by PIG-A mutations, leading to glycophosphatidylinositol (GPI)-anchored proteins deficiency that triggers hemolysis - a hallmark of the disease. PNH diagnostics is based on high-sensitivity multicolor flow cytometry (MFC), enabling to detect even small populations of PNH cells. In this single-center, retrospective study, we aimed to characterize a cohort of PNH clone-positive patients first time screened from January 1st, 2013 until December 31st, 2022 with MFC according to International Clinical Cytometry Society PNH Consensus Guidelines.</p><p><strong>Results: </strong>Out of 2790 first-time screened individuals, the presence of PNH clone in neutrophils was detected in 322 patients, including 49 children and 273 adults. Annual incidence was stable at a median of 31 patients (14 and 19 with clone sizes ≤ 1% and > 1%, respectively), with a decline in number of patients with clone sizes > 1% observed in 2020, potentially influenced by the COVID-19 pandemic. The most common screening indications were aplastic anemia and other cytopenias.</p><p><strong>Conclusions: </strong>A significant underrepresentation of hemolytic patients was observed as compared to the published cohorts suggesting that these patients are missed in diagnostic process and classic PNH remains underdiagnosed in Poland.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11256427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.1186/s13023-024-03237-3
Moeenaldeen AlSayed, Dia Arafa, Huda Al-Khawajha, Manal Afqi, Nouriya Al-Sanna'a, Rawda Sunbul, Maha Faden
Background: Mucopolysaccharidosis type IVa (Morquio A syndrome) and mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) are rare inherited lysosomal storage diseases associated with significant functional impairment and a wide spectrum of debilitating clinical manifestations. These conditions are thought to have higher-than-average prevalence rates in Saudi Arabia due to high rates of consanguineous marriage in the country. There are several unmet needs associated with the management of these diseases in Saudi Arabia.
Main body: The aim of this manuscript is to contextualize unmet management needs and provide recommendations to optimize diagnosis, multidisciplinary care delivery, and local data generation in this disease area. An expert panel was assembled comprising seven consultant geneticists from across Saudi Arabia. The Delphi methodology was used to obtain a consensus on statements relating to several aspects of mucopolysaccharidosis types IVa and VI. A consensus was reached for all statements by means of an online, anonymized voting system. The consensus statements pertain to screening and diagnosis, management approaches, including recommendations pertaining to enzyme replacement therapy, and local data generation.
Conclusion: The consensus statements presented provide specific recommendations to improve diagnostic and treatment approaches, promote multidisciplinary care and data sharing, and optimize the overall management of these rare inherited diseases in Saudi Arabia.
背景:粘多糖病 IVa 型(莫基奥 A 综合征)和粘多糖病 VI 型(马罗蒂-拉米综合征)是一种罕见的遗传性溶酶体储积病,具有严重的功能障碍和多种临床表现。由于沙特阿拉伯的近亲结婚率较高,这些疾病在该国的发病率被认为高于平均水平。在沙特阿拉伯,与这些疾病的治疗相关的一些需求尚未得到满足:本手稿旨在介绍未满足的管理需求,并提出建议,以优化诊断、多学科护理服务以及该疾病领域的本地数据生成。我们组建了一个专家小组,由来自沙特阿拉伯各地的七名遗传学顾问组成。专家组采用德尔菲法就与粘多糖病 IVa 型和 VI 型的几个方面有关的声明达成共识。通过匿名在线投票系统就所有声明达成共识。共识声明涉及筛查和诊断、管理方法(包括有关酶替代疗法的建议)以及本地数据生成:所提交的共识声明提供了具体建议,以改进诊断和治疗方法,促进多学科护理和数据共享,并优化沙特阿拉伯对这些罕见遗传性疾病的整体管理。
{"title":"Consensus-based expert recommendations on the management of MPS IVa and VI in Saudi Arabia.","authors":"Moeenaldeen AlSayed, Dia Arafa, Huda Al-Khawajha, Manal Afqi, Nouriya Al-Sanna'a, Rawda Sunbul, Maha Faden","doi":"10.1186/s13023-024-03237-3","DOIUrl":"10.1186/s13023-024-03237-3","url":null,"abstract":"<p><strong>Background: </strong>Mucopolysaccharidosis type IVa (Morquio A syndrome) and mucopolysaccharidosis type VI (Maroteaux-Lamy syndrome) are rare inherited lysosomal storage diseases associated with significant functional impairment and a wide spectrum of debilitating clinical manifestations. These conditions are thought to have higher-than-average prevalence rates in Saudi Arabia due to high rates of consanguineous marriage in the country. There are several unmet needs associated with the management of these diseases in Saudi Arabia.</p><p><strong>Main body: </strong>The aim of this manuscript is to contextualize unmet management needs and provide recommendations to optimize diagnosis, multidisciplinary care delivery, and local data generation in this disease area. An expert panel was assembled comprising seven consultant geneticists from across Saudi Arabia. The Delphi methodology was used to obtain a consensus on statements relating to several aspects of mucopolysaccharidosis types IVa and VI. A consensus was reached for all statements by means of an online, anonymized voting system. The consensus statements pertain to screening and diagnosis, management approaches, including recommendations pertaining to enzyme replacement therapy, and local data generation.</p><p><strong>Conclusion: </strong>The consensus statements presented provide specific recommendations to improve diagnostic and treatment approaches, promote multidisciplinary care and data sharing, and optimize the overall management of these rare inherited diseases in Saudi Arabia.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-17DOI: 10.1186/s13023-024-03276-w
Joshua L Bonkowsky, Bridget Healey, Naomi C Sacks, Ronaé McLin, Philip L Cyr, Eileen K Sawyer, Christopher D Stephen, Florian Eichler
Background: Adrenomyeloneuropathy (AMN) is a neurodegenerative disease phenotype of X-linked adrenoleukodystrophy (ALD), resulting in progressive myeloneuropathy causing spastic paraparesis, sensory ataxia, and bowel/bladder symptoms. We conducted a retrospective cohort study using two large administrative databases to characterize mortality and the burden of illness in adult men with AMN in the US.
Results: Healthcare resource use was assessed using a national commercial insurance claims database (2006-2021). Males with AMN ages 18-64 years and no evidence of cerebral ALD or other peroxisomal disorders were included and 1:4 matched on demographic characteristics to individuals without AMN. All study participants were followed for as long as observable. Patients with AMN were also identified in the Medicare Limited Dataset (2017-2022); mortality and age at death were compared with all Medicare enrollees. We identified 303 commercially insured men with AMN. Compared with non-AMN, individuals with AMN had significantly more inpatient hospital admissions (0.44 vs. 0.04 admissions/patient/year), outpatient clinic (8.88 vs. 4.1 visits/patient/year), outpatient hospital (5.33 vs. 0.99 visits/patient/year), and home healthcare visits (4.66 vs. 0.2 visits/patient/year), durable medical equipment claims (0.7 vs. 0.1 claims/patient/year), and prescription medication fills (18.1 vs. 5.4 fills/patient/year) (all p < 0.001). Average length-of-stay per hospitalization was also longer in AMN (8.88 vs. 4.3 days; p < 0.001). Rates of comorbidities were significantly more common in AMN compared to controls, including peripheral vascular disease (4.6% vs. 0.99%), chronic pulmonary disease (6.3% vs. 2.6%), and liver disease (5.6% vs. 0.88%), all p < 0.001. Among individuals age < 65 with Medicare disability coverage, mortality rates were 5.3x higher for adult AMN males (39.3% vs. 7.4%) and the age at death significantly younger (47.0 ± 11.3 vs. 56.5 ± 7.8 years), both p < 0.001. Among Medicare beneficiaries ages ≥ 65 mortality rates were 2.2x higher for men with AMN vs. those without AMN (48.6% vs. 22.4%), p < 0.001.
Conclusion: AMN imposes a substantial and underrecognized health burden on men, with higher healthcare utilization, greater medical comorbidity, higher mortality rates, and younger age at death.
背景:肾上腺肌髓神经病(AMN)是X连锁肾上腺白质营养不良症(ALD)的一种神经退行性疾病表型,会导致进行性肌髓神经病,引起痉挛性瘫痪、感觉共济失调和肠/膀胱症状。我们利用两个大型行政数据库开展了一项回顾性队列研究,以了解美国成年男性 AMN 患者的死亡率和疾病负担:我们使用全国商业保险理赔数据库(2006-2021 年)对医疗资源使用情况进行了评估。研究对象包括年龄在 18-64 岁之间、无脑 ALD 或其他过氧化物酶体疾病证据的 AMN 男性患者,他们与无 AMN 患者的人口统计学特征比例为 1:4。对所有研究参与者进行了长期跟踪观察。在医疗保险有限数据集(2017-2022 年)中也发现了 AMN 患者;死亡率和死亡年龄与所有医疗保险参保者进行了比较。我们发现了 303 名患有 AMN 的商业保险男性患者。与非 AMN 患者相比,AMN 患者的住院次数(0.44 次/患者/年 vs. 0.04 次/患者/年)、门诊次数(8.88 次/患者/年 vs. 4.1 次/患者/年)、门诊医院次数(5.33 次/患者/年 vs. 0.99 人次/患者/年)、家庭保健就诊(4.66 人次/患者/年 vs. 0.2 人次/患者/年)、耐用医疗设备索赔(0.7 vs. 0.1 索赔/患者/年)和处方药配药(18.1 vs. 5.4 配药/患者/年)(均为 p 结论:AMN 对患者造成了巨大且过低的医疗费用:急性髓系白血病给男性带来了巨大的健康负担,但这一负担并未得到充分认识,因为他们需要更多的医疗保健服务、更高的医疗并发症、更高的死亡率以及更年轻的死亡年龄。
{"title":"Burden of illness and mortality in men with Adrenomyeloneuropathy: a retrospective cohort study.","authors":"Joshua L Bonkowsky, Bridget Healey, Naomi C Sacks, Ronaé McLin, Philip L Cyr, Eileen K Sawyer, Christopher D Stephen, Florian Eichler","doi":"10.1186/s13023-024-03276-w","DOIUrl":"10.1186/s13023-024-03276-w","url":null,"abstract":"<p><strong>Background: </strong>Adrenomyeloneuropathy (AMN) is a neurodegenerative disease phenotype of X-linked adrenoleukodystrophy (ALD), resulting in progressive myeloneuropathy causing spastic paraparesis, sensory ataxia, and bowel/bladder symptoms. We conducted a retrospective cohort study using two large administrative databases to characterize mortality and the burden of illness in adult men with AMN in the US.</p><p><strong>Results: </strong>Healthcare resource use was assessed using a national commercial insurance claims database (2006-2021). Males with AMN ages 18-64 years and no evidence of cerebral ALD or other peroxisomal disorders were included and 1:4 matched on demographic characteristics to individuals without AMN. All study participants were followed for as long as observable. Patients with AMN were also identified in the Medicare Limited Dataset (2017-2022); mortality and age at death were compared with all Medicare enrollees. We identified 303 commercially insured men with AMN. Compared with non-AMN, individuals with AMN had significantly more inpatient hospital admissions (0.44 vs. 0.04 admissions/patient/year), outpatient clinic (8.88 vs. 4.1 visits/patient/year), outpatient hospital (5.33 vs. 0.99 visits/patient/year), and home healthcare visits (4.66 vs. 0.2 visits/patient/year), durable medical equipment claims (0.7 vs. 0.1 claims/patient/year), and prescription medication fills (18.1 vs. 5.4 fills/patient/year) (all p < 0.001). Average length-of-stay per hospitalization was also longer in AMN (8.88 vs. 4.3 days; p < 0.001). Rates of comorbidities were significantly more common in AMN compared to controls, including peripheral vascular disease (4.6% vs. 0.99%), chronic pulmonary disease (6.3% vs. 2.6%), and liver disease (5.6% vs. 0.88%), all p < 0.001. Among individuals age < 65 with Medicare disability coverage, mortality rates were 5.3x higher for adult AMN males (39.3% vs. 7.4%) and the age at death significantly younger (47.0 ± 11.3 vs. 56.5 ± 7.8 years), both p < 0.001. Among Medicare beneficiaries ages ≥ 65 mortality rates were 2.2x higher for men with AMN vs. those without AMN (48.6% vs. 22.4%), p < 0.001.</p><p><strong>Conclusion: </strong>AMN imposes a substantial and underrecognized health burden on men, with higher healthcare utilization, greater medical comorbidity, higher mortality rates, and younger age at death.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11253437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-15DOI: 10.1186/s13023-024-03278-8
Chanyan Huang, Yuanjia Zhang, Daniel A Diedrich, Jiawen Li, Wei Luo, Xu Zhao, Yuting Guo, Yijun Luo, Tao Zhang, Xuan Wang, Wenqi Huang, Ying Xiao
Background: Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture.
Methods: Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed.
Results: Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture.
Conclusions: The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.
{"title":"A horizontal and perpendicular interlaminar approach for intrathecal nusinersen injection in patients with spinal muscular atrophy and scoliosis: an observational study.","authors":"Chanyan Huang, Yuanjia Zhang, Daniel A Diedrich, Jiawen Li, Wei Luo, Xu Zhao, Yuting Guo, Yijun Luo, Tao Zhang, Xuan Wang, Wenqi Huang, Ying Xiao","doi":"10.1186/s13023-024-03278-8","DOIUrl":"10.1186/s13023-024-03278-8","url":null,"abstract":"<p><strong>Background: </strong>Lumbar puncture is challenging for patients with scoliosis. Previous ultrasound-assisted techniques for lumbar puncture used the angle of the probe as the needle trajectory; however, reproducing the angle is difficult and increases the number of needle manipulations. In response, we developed a technique that eliminated both the craniocaudal and lateromedial angulation of the needle trajectory to overall improve this technique. We assessed the feasibility and safety of this method in patients with scoliosis and identify factors related to difficult lumbar puncture.</p><p><strong>Methods: </strong>Patients with spinal muscular atrophy and scoliosis who were referred to the anesthesia department for intrathecal nusinersen administrations were included. With a novel approach that utilized patient position and geometry, lumbar puncture was performed under ultrasound guidance. Success rates, performance times and adverse events were recorded. Clinical-demographic and spinal radiographic data pertaining to difficult procedures were analyzed.</p><p><strong>Results: </strong>Success was achieved in all 260 (100%) lumbar punctures for 44 patients, with first pass and first attempt success rates of 70% (183/260) and 87% (226/260), respectively. Adverse events were infrequent and benign. Higher BMI, greater skin dural sac depth and smaller interlaminar size might be associated with greater difficulty in lumbar puncture.</p><p><strong>Conclusions: </strong>The novel ultrasound-assisted horizontal and perpendicular interlaminar needle trajectory approach is an effective and safe method for lumbar puncture in patients with spinal deformities. This method can be reliably performed at the bedside and avoids other more typical and complex imaging such as computed tomography guided procedure.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11250962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}