New onset refractory status epilepticus (NORSE), including its subtype with a preceding febrile illness known as febrile infection-related epilepsy syndrome (FIRES), is one of the most severe forms of status epilepticus. The exact causes of NORSE are currently unknown, and there is so far no disease-specific therapy. Identifying the underlying pathophysiology and discovering specific biomarkers, whether immunologic, infectious, genetic, or other, may help physicians in the management of patients with NORSE. A broad spectrum of biomarkers has been proposed for status epilepticus patients, some of which were evaluated for patients with NORSE. Nonetheless, none has been validated, due to significant variabilities in study cohorts, collected biospecimens, applied analytical methods, and defined outcome endpoints, and to small sample sizes. The NORSE Institute established an open NORSE/FIRES biorepository for health-related data and biological samples allowing the collection of biospecimens worldwide, promoting multicenter research and sharing of data and specimens. In this report are standard operating procedures for biospecimen collection and biobanking in this rare condition suggested. Also are criteria for the appropriate use of previously collected biospecimens proposed. It is predicted that the widespread use of standardized procedures will reduce heterogeneity, facilitate the future identification of validated biomarkers for NORSE, and provide a better understanding of the pathophysiology and best clinical management for these patients. Read the full article here.
Traditional clinical trials require tests and procedures that are administered in centralized clinical research sites, which are beyond the standard of care that patients receive for their rare and chronic diseases. The limited number of rare disease patients scattered around the world makes it particularly challenging to recruit participants and conduct these traditional clinical trials.
Participating in clinical research can be burdensome, especially for children, the elderly, physically and cognitively impaired individuals who require transportation and caregiver assistance, or patients who live in remote locations or cannot afford transportation. In recent years, there is an increasing need to consider Decentralized Clinical Trials as a participant-centric approach that uses new technologies and innovative procedures for interaction with participants in the comfort of their home.
This report discusses the planning and conduct of Decentralized Clinical Trials, which can increase the quality of trials with a specific focus on rare diseases. Read the full article here.
CLN3 disease, caused by biallelic mutations in the CLN3 gene, is a rare pediatric neurodegenerative disease that has no cure or disease modifying treatment. The development of effective treatments has been hindered by a lack of etiological knowledge, but gene replacement has emerged as a promising therapeutic platform for such disorders. In this research a mouse model of CLN3 disease to test the safety and efficacy of a cerebrospinal fluid-delivered AAV9 gene therapy with a study design optimized for translatability is used. In this model, postnatal day one administration of the gene therapy virus resulted in robust expression of human CLN3 throughout the CNS over the 24-month duration of the study. A range of histopathological and behavioral parameters are assayed, with the therapy consistently and persistently rescuing a number of hallmarks of disease while being safe and well-tolerated. Together, the results show great promise for translation of the therapy into the clinic, prompting the launch of a first-in-human clinical trial. Read the full article here.
Acquired haemophilia A is a rare disease with an annual incidence of 1.48 per million. Based on clinical observations, in this article a higher incidence in southern Switzerland is suspected, and its aim is to provide local epidemiological data, and clinical information regarding diagnosis, treatment and outcome in this region. All adult patients with acquired haemophilia A treated between 2013 and 2019 in a medical establishment in southern Switzerland are included in the present retrospective analysis.
11 patients with acquired haemophilia A between 2013 and 2019 are treated, resulting in an annual incidence of 4.5 per million. Median delay from first symptoms to diagnosis was 4.5 days, and the median age at diagnosis is 79 years. Possible causative conditions were: pregnancy, polyarteritis nodosa, myelodysplastic syndrome, chronic human immunodeficiency virus (HIV), and HIV postexposure prophylaxis. In five patients no underlying or associated condition was identified. All patients had bleeding symptoms, 5/10 patients had major bleedings, and 7/10 patients were treated with bypassing agents. All patients received corticosteroids; 7/10 patients received immunosuppressive combination therapy.
Acquired haemophilia A is a rare disease, but manageable despite the advanced patient age and comorbidities. Its incidence in Southern Switzerland is higher than previously suspected. Read the full article here.
For the 14th year in a row, the National Conference on Rare Diseases and Orphan Drugs, organized by the Institute for Rare Diseases, is about to be held. The event is an annual forum that brings together all stakeholders – medical professionals, patients, medical students, industry representatives and health authorities – to present and discuss the latest developments in the diagnosis, treatment and follow-up of rare diseases, the development of European reference networks and access to innovation.
Place: Hotel “Imperial” – Plovdiv
Early bird registration deadline: August 1, 2023
Late registration deadline: September 15, 2023
Deadline for submission of abstracts: September 1, 2023
To contact the organizing committee: congress@raredis.org
Additional information can be found at XIV NATIONAL CONFERENCE ON RARE DISEASES AND ORPHAN DRUGS – Virtual Congress Center (raredis.org)
This document provides a comprehensive summary of evidence on the current situation of rare diseases (RDs) globally and regionally, including conditions, practices, policies, and regulations, as well as the challenges and barriers faced by RD patients, their families, and caregivers. The document builds on a review of academic literature and policies and a process of validation and feedback by a group of seven experts from across the globe. The document is divided into five main sections: methodology and objective; background and context; overview of the current situation and key challenges related to RDs covering six dimensions: burden of disease, patient journey, social impact, disease management, RD-related policies, and research and development; recommendations; and conclusions. The recommendations are derived from the discussion undertaken by the experts on the findings of this review and provide a set of actionable solutions to the challenges and barriers to improving access to RD diagnosis and treatment around the world. The recommendations can support critical decision-making, guiding efforts by a broad range of RDs stakeholders, including governments, international organizations, manufacturers, researchers, and patient advocacy groups. Read the full article here.
The manifestations of Phelan-McDermid syndrome (PMS) are complex, warranting expert and multidisciplinary care in all life stages. In this report consensus recommendations on the organization of care for individuals with PMS are proposed. It is indicated that care should consider all life domains, which can be done within the framework of the International Classification of Functioning, Disability and Health (ICF). This framework assesses disability and functioning as the outcome of the individual’s interactions with other factors. The different roles within care, such as performed by a centre of expertise, by regional health care providers and by a coordinating physician are addressed. A surveillance scheme and emergency card is provided and disciplines participating in a multidisciplinary team for PMS are described. Additionally, recommendations are provided for transition from paediatric to adult care. This care proposition may also be useful for individuals with other rare genetic neurodevelopmental disorders. Read the full article here.
Sweet syndrome (SS) is a rare disease described as a febrile neutrophilic dermatosis with acute onset, the pathogenesis of which has not yet been elucidated. The syndrome is characterized by the sudden onset of erythematous infiltrated papules or plaques located on the upper body and is associated with fever, leukocytosis and neutrophilia. The lesions show a dense dermal infiltration with mature neutrophils. The condition is responsive to systemic steroids. The central nervous system, bones, muscles, eyes, ears, mouth, heart, lung, liver, kidneys, intestines, and spleen may be affected by SS as extracutaneous manifestations. Up to 80% of SS cases are associated with hematological diseases, predominantly myelodysplastic syndrome (MDS). Myelodysplastic syndrome is a clonal disease of the bone marrow characterized by inefficient hematopoiesis, dysplasia of the bone marrow and peripheral cytopenias. After analyzing later studies and current practical aspects regarding MDS-related SS, in this report an algorithm for evaluating these patients is suggested. Read the full article here.
Idiopathic systemic capillary leak syndrome (ISCLS) is a rare disease characterized by recurrent episodes of acute life-threatening attacks of shock, hemoconcentration, and hypoalbuminemia. Increase in capillary permeability results in reversible plasma movement into the interstitial spaces followed by appearance of related symptoms or complications, including renal failure. This condition can be potentially life-threatening; however, it is easily misdiagnosed.
A 47-year-old man with no previous medical history presented to the emergency department after experiencing general weakness and abdominal pain. He develops hypovolemic shock within 3 h of presentation and initial laboratory tests showed hemoconcentration, hypoalbuminemia and acute kidney injury. Following vigorous fluid therapy and supportive care, the patient recovers, but a similar episode recurrs after 4 months without any specific trigger. Based on the combined clinical manifestations and laboratory findings of both the attacks, he is diagnosed with ISCLS. Symptomatic relief is achieved via oxygen supplementation and massive volume replacement using normal saline and the patient is prescribed bambuterol 10 mg and theophylline 400 mg once-a-day. He is discharged from the hospital on day 5 of hospitalization. Thereafter, the patient is being followed for 5 years without any symptoms or recurrence of ISCLS even in the situation of COVID-19 infection.
ISCLS is an extremely infrequent and commonly misdiagnosed disease. However, early diagnosis, treatment and prophylaxis through accumulated clinical data can prevent ISCLS recurrence and the development of related fatal complications. Therefore, clinicians need to be well aware of the variety of clinical characteristics and treatment options of this disease. Read the full article here.
Advances in the study of ultra-rare genetic conditions are leading to the development of targeted interventions developed for single or very small numbers of patients. Due to the experimental but also highly individualized nature of these interventions, they are difficult to classify cleanly as either research or clinical care. The goal of this report is to understand how parents, IRB members, and clinical geneticists familiar with individualized genetic interventions conceptualize these activities and their implications for the relationship between research and clinical care.
In this report, qualitative, semi-structured interviews with 28 parents, IRB members, and clinical geneticists are conducted, and themes from those interviews through content analysis are derived.
Individualized interventions aimed at one or few patients reveal the limitations of a binary framing of research and clinical care. As a hybrid set of activities, individualized interventions suggest the need for flexibility and new frameworks that acknowledge these activities across the spectrum of research and clinical care. Read the full article here.