Therapeutic advances in rare disease最新文献

{"title":"Etranacogene dezaparvovec for hemophilia B gene therapy.","authors":"Courtney D Thornburg","doi":"10.1177/26330040211058896","DOIUrl":"10.1177/26330040211058896","url":null,"abstract":"<p><p>The treatment landscape for hemophilia has been rapidly changing with introduction of novel therapies. Gene therapy for hemophilia is a promising therapeutic option for sustained endogenous factor production to mitigate the need for prophylactic treatment to prevent spontaneous and traumatic bleeding. Etranacogene dezaparvovec is an investigational factor IX (FIX) gene transfer product that utilizes the adeno-associated virus (AAV) 5 vector with a liver-specific promoter and a hyperactive FIX transgene. Here, the development of etranacogene dezaparvovec and available efficacy and safety data from clinical trials are reviewed. Overall, etranacogene dezaparvovec provides sustained FIX expression for more than 2 years and allows for a bleed and infusion-free life in the majority of patients. Safety, efficacy, and quality-of-life data will inform shared decision-making for patients who are considering gene therapy. Long-term follow-up regarding duration of expression and safety are crucial.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211058896"},"PeriodicalIF":0.0,"publicationDate":"2021-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a2/ec/10.1177_26330040211058896.PMC10032433.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marfan syndrome and the eye clinic: from diagnosis to management.","authors":"Haseeb Akram,&nbsp;Jose Antonio Aragon-Martin,&nbsp;Aman Chandra","doi":"10.1177/26330040211055738","DOIUrl":"10.1177/26330040211055738","url":null,"abstract":"<p><p>Marfan syndrome (MFS) is an autosomal dominantly inherited disorder affecting the cardiovascular, ocular and musculoskeletal systems. Frequently, clinical suspicion and subsequent diagnosis begins in the ophthalmology clinic. Importantly, the ophthalmologist has a responsibility to cater not only to the eye, but also to be involved in a holistic approach for these patients. In this review, we discuss how MFS may present to an eye clinic, including clinical features, ocular morbidity, genetic diagnosis and management. Although this condition is ideally managed by a multidisciplinary team, our focus will be on MFS and the eye, including other conditions which may present with similar phenotypes. The ophthalmologist's role as the potential first contact for a patient with suspected MFS is crucial in making the proper investigations and referral, with the knowledge that not all ectopia lentis cases are MFS and vice versa. Management of ocular conditions in MFS may range from simple observation to surgical intervention; current options will be discussed.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211055738"},"PeriodicalIF":0.0,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/d3/10.1177_26330040211055738.PMC10032431.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving patient informed consent for haemophilia gene therapy: the case for change.","authors":"Laurence Woollard,&nbsp;Richard Gorman,&nbsp;Dakota J Rosenfelt","doi":"10.1177/26330040211047244","DOIUrl":"10.1177/26330040211047244","url":null,"abstract":"<p><p>Adeno-associated virus-based gene therapy points to a coming transformation in the treatment of people living with haemophilia, promising sustained bleed control and potential improvement in quality of life. Nevertheless, the consequences of introducing new genetic material are not trivial. The perceived benefits should not minimise the challenges facing patients in understanding the long-term risks and providing a valid and meaningful informed consent, whether in a research or clinical setting. Informed consent is a fundamentally important doctrine in both medical ethics and health law, upholding an individual's right to define their personal goals and make their own autonomous choices. Patients should be enabled to recognise their clinical situation, understand the implications of treatment and integrate every facet of their life into their decision. This review describes informed consent processes for haemophilia gene therapy clinical trials, factors affecting patients' decision making and the availability of patient-centred decision support interventions, to ensure that patients' interests are being protected. Regulatory guidance has been published for physicians and manufacturers in haemophilia on informed consent, including for gene therapy, while best-practice recommendations for patient-physician discussions are available. In all settings, however, communicating and presenting highly technical and complex therapeutic information is challenging, especially where multiple barriers to scientific knowledge and health literacy exist. We propose several evidence-informed strategies to enhance the consent procedure, such as utilising validated literacy and knowledge assessment tools as well as participatory learning environments over an extended period, to ensure that patients are fully cognisant of the consent they give or deny. Further research is needed to define new, creative approaches for patient education and the upholding of ethical values in the informed consent process for gene therapy. The lessons learnt and approaches developed within haemophilia could set the gold standard for good practice in ensuring ethical preparedness amidst advances in genetic therapies.</p><p><strong>Plain language summary: </strong><i>Improving the informed consent process for people living with haemophilia considering gene therapy.</i> Gene therapy is the process of replacing faulty genes with healthy ones. In haemophilia, gene therapy involves introducing a working copy of the gene for the clotting factor that patients are missing. Following treatment, patients should begin producing their own clotting factor normally. However, people living with haemophilia (PwH) need to be fully informed regarding the potential benefits and risks of gene therapy and what this means for them, whether as part of a research study or routine medical care.Patients must be respected and supported to make decisions about their own health and wellbeing, recognising their l","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211047244"},"PeriodicalIF":0.0,"publicationDate":"2021-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/de/62/10.1177_26330040211047244.PMC10032461.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9839547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing telehealth to create a clinical model of care for patients with Batten disease and other rare diseases.","authors":"Jessica F Scherr,&nbsp;Charles Albright,&nbsp;Emily de Los Reyes","doi":"10.1177/26330040211038564","DOIUrl":"10.1177/26330040211038564","url":null,"abstract":"<p><p>The COVID-19 pandemic transformed the delivery of healthcare across the world. Telehealth has emerged as the primary method for providing healthcare early in the pandemic. Patient and healthcare provider views of the effectiveness of telehealth services are encouraging and support the long-term use of telehealth services in clinical practice. Telehealth may provide a strategy that has far-reaching benefits for diverse patient populations, such as patients with Batten disease and other rare diseases, who face additional barriers to accessing subspecialty healthcare services. The aims of this paper, through the experience of a single Batten Disease Center of Excellence, are to (1) review the benefits and barriers involved in the delivery of telehealth services to patients with rare diseases; (2) discuss components of a model for clinical care that utilizes telehealth services for patients with Batten disease; (3) discuss limitations and future directions of using telehealth in patients with rare diseases. Healthcare systems should consider building clinical models that utilize telehealth services to provide multidisciplinary services to patients with rare diseases. There are numerous benefits in using telehealth that can enhance and expand service delivery between the patient and clinician. Telehealth services can also improve provider-to-provider communication and collaboration when providing clinical care to individuals with rare diseases. Although there are many benefits to utilizing telehealth services in provision of care to patients with rare diseases, it is important to consider factors that may limit or add additional barriers prior to implementing telehealth services. There is a need for future collaborative research to examine and compare the effectiveness and outcomes of telehealth services with standard of care services that are provided in-person. Future research should also examine how to reduce the challenges and barriers associated with the implementation of telehealth services.</p><p><strong>Plain language summary: </strong><b>What is telehealth?</b> Telehealth is defined by the US Department of Health Resources and Services Administrations¹ as the \"use of electronic information and telecommunication technologies to support long-distance clinical healthcare, patient and professional health-related education, public health, and health administration. Technologies include video conference, the internet, store-and-forward imaging, streaming media, and terrestrial and wireless communication.\" <b>What was the aim of this review?</b> This review was conducted to guide a clinical model using telehealth services for patients with Batten disease and other rare diseases based on the experiences of a single Batten Disease Center of Excellence. <b>Why is this important?</b> Individuals with rare diseases may face multiple barriers to accessing clinical services. Local doctors and treatment providers, such as speech therapists,","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211038564"},"PeriodicalIF":0.0,"publicationDate":"2021-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f7/85/10.1177_26330040211038564.PMC10032454.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9468603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wolfram syndrome: new pathophysiological insights and therapeutic strategies.","authors":"Ratnakar Mishra,&nbsp;Benson S Chen,&nbsp;Prachi Richa,&nbsp;Patrick Yu-Wai-Man","doi":"10.1177/26330040211039518","DOIUrl":"10.1177/26330040211039518","url":null,"abstract":"<p><p>Wolfram Syndrome (WS) is an ultra-rare, progressive neurodegenerative disease characterized by early-onset diabetes mellitus and irreversible loss of vision, secondary to optic nerve degeneration. Visual loss in WS is an important cause of registrable blindness in children and young adults and the pathological hallmark is the preferential loss of retinal ganglion cells within the inner retina. In addition to optic atrophy, affected individuals frequently develop variable combinations of neurological, endocrinological, and psychiatric complications. The majority of patients carry recessive mutations in the <i>WFS1</i> (4p16.1) gene that encodes for a multimeric transmembrane protein, wolframin, embedded within the endoplasmic reticulum (ER). An increasingly recognised subgroup of patients harbor dominant <i>WFS1</i> mutations that usually cause a milder phenotype, which can be limited to optic atrophy. Wolframin is a ubiquitous protein with high levels of expression in retinal, neuronal, and muscle tissues. It is a multifunctional protein that regulates a host of cellular functions, in particular the dynamic interaction with mitochondria at mitochondria-associated membranes. Wolframin has been implicated in several crucial cellular signaling pathways, including insulin signaling, calcium homeostasis, and the regulation of apoptosis and the ER stress response. There is currently no cure for WS; management remains largely supportive. This review will cover the clinical, genetic, and pathophysiological features of WS, with a specific focus on disease models and the molecular pathways that could serve as potential therapeutic targets. The current landscape of therapeutic options will also be discussed in the context of the latest evidence, including the pipeline for repurposed drugs and gene therapy.</p><p><strong>Plain language summary: </strong><b>Wolfram syndrome - disease mechanisms and treatment options</b> Wolfram syndrome (WS) is an ultra-rare genetic disease that causes diabetes mellitus and progressive loss of vision from early childhood. Vision is affected in WS because of damage to a specialized type of cells in the retina, known as retinal ganglion cells (RGCs), which converge at the back of the eye to form the optic nerve. The optic nerve is the fast-conducting cable that transmits visual information from the eye to the vision processing centers within the brain. As RGCs are lost, the optic nerve degenerates and it becomes pale in appearance (optic atrophy). Although diabetes mellitus and optic atrophy are the main features of WS, some patients can develop more severe problems because the brain and other organs, such as the kidneys and the bladder, are also affected. The majority of patients with WS carry spelling mistakes (mutations) in the <i>WFS1</i> gene, which is located on the short arm of chromosome 4 (4p16.1). This gene is highly expressed in the eye and in the brain, and it encodes for a protein located within a compartment","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211039518"},"PeriodicalIF":0.0,"publicationDate":"2021-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6b/ac/10.1177_26330040211039518.PMC10032446.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473480","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New avenues for therapy in mitochondrial optic neuropathies.","authors":"Wing Sum Vincent Ng,&nbsp;Matthieu Trigano,&nbsp;Thomas Freeman,&nbsp;Carmine Varrichio,&nbsp;Dinesh Kumar Kandaswamy,&nbsp;Ben Newland,&nbsp;Andrea Brancale,&nbsp;Malgorzata Rozanowska,&nbsp;Marcela Votruba","doi":"10.1177/26330040211029037","DOIUrl":"10.1177/26330040211029037","url":null,"abstract":"<p><p>Mitochondrial optic neuropathies are a group of optic nerve atrophies exemplified by the two commonest conditions in this group, autosomal dominant optic atrophy (ADOA) and Leber's hereditary optic neuropathy (LHON). Their clinical features comprise reduced visual acuity, colour vision deficits, centro-caecal scotomas and optic disc pallor with thinning of the retinal nerve fibre layer. The primary aetiology is genetic, with underlying nuclear or mitochondrial gene mutations. The primary pathology is owing to retinal ganglion cell dysfunction and degeneration. There is currently only one approved treatment and no curative therapy is available. In this review we summarise the genetic and clinical features of ADOA and LHON and then examine what new avenues there may be for therapeutic intervention. The therapeutic strategies to manage LHON and ADOA can be split into four categories: prevention, compensation, replacement and repair. Prevention is technically an option by modifying risk factors such as smoking cessation, or by utilising pre-implantation genetic diagnosis, although this is unlikely to be applied in mitochondrial optic neuropathies due to the non-life threatening and variable nature of these conditions. Compensation involves pharmacological interventions that ameliorate the mitochondrial dysfunction at a cellular and tissue level. Replacement and repair are exciting new emerging areas. Clinical trials, both published and underway, in this area are likely to reveal future potential benefits, since new therapies are desperately needed.</p><p><strong>Plain language summary: </strong>Optic nerve damage leading to loss of vision can be caused by a variety of insults. One group of conditions leading to optic nerve damage is caused by defects in genes that are essential for cells to make energy in small organelles called mitochondria. These conditions are known as mitochondrial optic neuropathies and two predominant examples are called autosomal dominant optic atrophy and Leber's hereditary optic neuropathy. Both conditions are caused by problems with the energy powerhouse of cells: mitochondria. The cells that are most vulnerable to this mitochondrial malfunction are called retinal ganglion cells, otherwise collectively known as the optic nerve, and they take the electrical impulse from the retina in the eye to the brain. The malfunction leads to death of some of the optic nerve cells, the degree of vision loss being linked to the number of those cells which are impacted in this way. Patients will lose visual acuity and colour vision and develop a central blind spot in their field of vision. There is currently no cure and very few treatment options. New treatments are desperately needed for patients affected by these devastating diseases. New treatments can potentially arise in four ways: prevention, compensation, replacement and repair of the defects. Here we explore how present and possible future treatments might provide hope for th","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211029037"},"PeriodicalIF":0.0,"publicationDate":"2021-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26330040211029037","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9468608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme replacement therapy in lysosomal acid lipase deficiency (LAL-D): a systematic literature review.","authors":"Aamir Bashir,&nbsp;Pramil Tiwari,&nbsp;Ajay Duseja","doi":"10.1177/26330040211026928","DOIUrl":"10.1177/26330040211026928","url":null,"abstract":"<p><strong>Background: </strong>Lysosomal acid lipase deficiency (LAL-D) is a very rare genetic abnormality caused by LIPA gene mutation. The disease has two distinct clinical variants in humans: Wolman disease in infants and cholesteryl ester storage disease in children and adults. Both conditions are characterized by elevated serum transaminases, dyslipidaemia, severe liver steatosis and accelerated fibrosis or cirrhosis, contributing to its high rate of early mortality. Recently sebelipase alfa (recombinant human LAL) was launched to address its underlying pathology. This systematic review evaluates the safety and efficacy of sebelipase alfa for LAL-D.</p><p><strong>Methods: </strong>This systematic review was performed following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Clinical trial records were systematically searched in <i>PubMed/Medline</i>, <i>ClinicalTrials.gov., Cochrane Library</i> and <i>Google Scholar</i> up to September 2020. Records that have reported at least one of the included outcomes were included. Baseline and endpoint mean and standard deviation (SD) for all outcomes were recorded. For safety, frequency and overall distribution of different adverse events were included.</p><p><strong>Results: </strong>A total of seven records from five individual studies with 110 LAL-D patients were included into this study. The mean age ranged from 2.57 months in infants to 31.6 years among adults. Serum transaminases (alanine aminotransferase and aspartate aminotransferase), serum lipids (total cholesterol, triglycerides, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol), gamma-glutamyl transferase and liver volume were included as efficacy outcomes. Final pooled results were synthesized as a change from baseline to end of the treatment. A significant effect on both serum transaminases and other serum lipid was achieved (<i>p</i> < 0.01), while non-significant differences were seen for GGT and liver volume as <i>p</i> = 0.35 and <i>p</i> = 0.08 was observed. Mostly the adverse events related to the infusions were infrequent and mild-to-moderate in severity.</p><p><strong>Conclusion: </strong>Sebelipase alfa as an enzyme replacement provides an effective, safe and well tolerated treatment in both variants of LAL-D.</p><p><strong>Plain language summary: </strong><b>A systematic literature review on safety and efficacy of enzyme replacement therapy in lysosomal acid lipase deficiency</b> Lysosomal acid lipase deficiency (LAL-D) is a rare, progressive, genetic disorder caused by functional mutations in the LIPA gene, which encodes LAL enzyme. This enzyme maintains lipid homeostasis by hydrolysing the cholesterol esters and triglycerides. Patients with deficient LAL activity are seen with abnormal liver functions which keep them at a high risk of early mortality. Clinical diagnosis of this disease is very challenging due to both its low prevalence and low awareness among ","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211026928"},"PeriodicalIF":0.0,"publicationDate":"2021-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26330040211026928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9468607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"They've been BITTEN: reports of institutional and provider betrayal and links with Ehlers-Danlos Syndrome patients' current symptoms, unmet needs and healthcare expectations.","authors":"Jennifer Langhinrichsen-Rohling,&nbsp;Chrystal L Lewis,&nbsp;Sean McCabe,&nbsp;Emma C Lathan,&nbsp;Gabrielle A Agnew,&nbsp;Candice N Selwyn,&nbsp;Margaret E Gigler","doi":"10.1177/26330040211022033","DOIUrl":"10.1177/26330040211022033","url":null,"abstract":"<p><strong>Introduction: </strong>Patients with rare and/or care-intensive conditions, such as Ehlers-Danlos Syndrome (EDS), can pose challenges to their healthcare providers (HCPs). The current study used the BITTEN framework¹ to code EDS patients' open-ended written responses to a needs survey to determine their self-reported prevalence of healthcare institutional betrayal and its link with their expressed symptoms, provider perceptions, unmet needs, and on-going healthcare-related expectations.</p><p><strong>Methods: </strong>Patients with EDS (<i>n</i> = 234) were recruited <i>via</i> a rare disease electronic mailing list and snowball sampling. A total of one-hundred and six respondents (45.3%) endorsed having unmet healthcare-related needs; of these, 104 (99%) completed an open-ended prompt about these needs. Responses were coded for components of BITTEN, a framework designed to link patients' past, current, and future healthcare-related experiences in a trauma informed manner.</p><p><strong>Results: </strong>Many respondents with ongoing needs endorsed experiencing past institutional and provider betrayal (43%; <i>n</i> = 45), current mental health symptoms (91.4%; <i>n</i> = 95), negative expectations for future healthcare (40.4%; <i>n</i> = 62), and a lack of trust in their healthcare provider (22.1%; <i>n</i> = 23). There were no significant differences in post-traumatic stress disorder (PTSD)/anxiety, depression/sadness, or isolative symptoms between respondents coded for institutional betrayal (<i>n</i> = 45) compared with those not (<i>n</i> = 59). However, EDS respondents reporting institutional betrayal were significantly more likely to self-report anger and irritability symptoms, a lack of trust in their HCPs, and more negative expectations for future healthcare than those not reporting institutional betrayal.</p><p><strong>Discussion/conclusions: </strong>The frequent spontaneous reporting of past healthcare betrayals among patients with EDS implies the need for trauma-informed care and provider education. Given that experiences of institutional betrayal are associated with increased anger and irritability, as well as with negative expectations for future healthcare interactions, efforts to repair healthcare provider and system-wide relationship ruptures might have positive healthcare consequences.</p><p><strong>Plain language summary: </strong><b>Reports of Institutional and Provider Betrayal and Links with Ehlers-Danlos Syndrome Patients' Current Symptoms, Unmet Needs and Future Healthcare Expectations</b> <b>What is EDS?</b> Ehlers-Danlos Syndrome (EDS) refers to a group of rare genetic connective tissue disorders that are primarily characterized by skin hyperelasticity, joint hypermobility, and tissue fragility. Connective tissue is largely responsible for the structural integrity of our bodies, and there are several EDS subtypes which each describe a specific connective tissue problem. In addition, there is signif","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211022033"},"PeriodicalIF":0.0,"publicationDate":"2021-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26330040211022033","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9839548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IMPACT study: measuring the impact of caregiving on families and healthcare professionals of children and adults living with mucopolysaccharidoses in Ireland.","authors":"Suja Somanadhan,&nbsp;Hannah Bristow,&nbsp;Ellen Crushell,&nbsp;Gregory Pastores,&nbsp;Emma Nicholson,&nbsp;Thilo Kroll,&nbsp;Philip J Larkin,&nbsp;Aoife Brinkley","doi":"10.1177/26330040211020764","DOIUrl":"10.1177/26330040211020764","url":null,"abstract":"<p><strong>Introduction: </strong>Disease trajectories are often uncertain among individuals living with mucopolysaccharidoses (MPS) due to the progressive nature of the illness and the goal of care. This study investigated the impact on caregivers and care providers of children and adults living with MPS.</p><p><strong>Methods: </strong>The study used a cross-sectional design and a convenience sampling strategy which involved two sequential study components. The stage 1 quantitative component included three validated scales: the abbreviated World Health Organization Quality of Life (WHOQOL-BREF), the Paediatric Inventory for Parents (PIP) and the 14-item Resilience Scale (RS-14). The stage 2 qualitative component consisted of two focus groups with healthcare professionals (HCPs) (<i>n</i> = 9) working with children and adults living with MPS across three clinical sites in Ireland. Data were collected between November 2017 and July 2019.</p><p><strong>Results: </strong>A total of 31 parents identified as caregivers participated in this study. The mean quality of life (QoL) score was 93.81, indicating a significantly high QoL. The PIP frequency total mean was 102.74 and difficulty mean 104.94. The mean score for the RS-14 was notably high, 81.42 out of a maximum of 98. The majority of the results showed high levels of concern for the future, with just under 50% finding themselves very often feeling scared that their child's condition will deteriorate or that their child will die and finding these thoughts very difficult. The healthcare professionals' (HCPs) perceptions were focused on the complexity of MPS, coping strategies, managing expectations and support services.</p><p><strong>Conclusion: </strong>The overall findings of the study reinforced the need for sustained and enhanced psychological support to ensure both families of children and adults living with MPS and the HCPs are supported in the continued delivery of quality patient care and outcomes. Subjective and objective measures from family caregivers and HCPs yield results that can decrease stress and improve psychological support.</p><p><strong>Plain language summary: </strong><b>Impact of caregiving on families and healthcare professionals of children and adults living with mucopolysaccharidoses in Ireland</b> Mucopolysaccharidoses (MPS) is a group of one of the many rare inherited metabolic disorders that come under category three of life-limiting conditions. Children born with this genetic condition show no change at birth, but effects start to show in subsequent years as it is a progressive disease. The severity of the condition varies according to the specific type, ranging from very mild symptoms to, in most cases, multisystemic, restricted growth or mental and physical disabilities. Recent developments in treatments for some forms of MPS have dramatically changed the quality of life (QoL) for patients. Other forms of treatment are currently under investigation and development. T","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211020764"},"PeriodicalIF":0.0,"publicationDate":"2021-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26330040211020764","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wiskott-Aldrich syndrome with normal platelet volume in a low-income setting: a case report.","authors":"William Frank Mawalla,&nbsp;Hamisa Iddy,&nbsp;Christine Aloyce Kindole,&nbsp;Ahlam Nasser,&nbsp;Anna Schuh","doi":"10.1177/26330040211009905","DOIUrl":"10.1177/26330040211009905","url":null,"abstract":"<p><p>Wiskott-Aldrich syndrome (WAS) is a rare immunodeficiency X-linked genetic disorder. It is often featured with a clinical triad of thrombocytopenia with low mean platelet volume, eczematoid dermatitis and recurrent infections. The clinical manifestation of WAS, depending on the underlying variant, shows wide heterogeneity. We present a case of a 10-month-old boy who came in with a history of recurrent fever, skin lesions since birth and episodes of bloody diarrhoea. He had severe anaemia and thrombocytopenia (with normal mean platelet volume). Genetic analysis revealed the patient to be hemizygous for a pathogenic WAS gene splice variant (NM_000377.2:c.360+1G>A). He was managed with supportive treatment and regular follow up, but died 4 months later. As it is a rare genetic disease, the diagnosis of WAS can easily be missed, especially in settings with scarce healthcare resources that do not have easy access to genetic testing. Thus, a high index of suspicion is needed when a male child presents with recurrent infections and bleeding tendencies.</p><p><strong>Plain language summary: </strong>Management challenges of a rare genetic disorder in a resource-limited country: a case report of Wiskott-Aldrich syndrome in TanzaniaWiskott-Aldrich syndrome (WAS) is a rare inherited disease that mainly affects boys. Patients will typically present with low levels of a single line of little particles of cells that clot the blood called platelets, whole-body skin rashes and recurrent infections. Nevertheless, the clinical presentation can vary between individuals. We present a case of a 10-month-old boy who came in with a history of recurrent fever, skin rash since birth and episodes of bloody diarrhoea. He had very low levels of red blood cells and platelets. Genetic analysis confirmed the patient to have WAS. He was managed with supportive treatment, followed up on a regular clinic but unfortunately died 4 months later. Being a rare genetic disease, the diagnosis of WAS can easily be missed, especially in regions with scarce healthcare resources that do not have easy access to genetic testing. Thus, doctors should suspect WAS in boys presenting with recurrent infections and bleeding problems.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211009905"},"PeriodicalIF":0.0,"publicationDate":"2021-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/26330040211009905","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9468604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}