Chirurgie (Heidelb). 2023 Aug 14. doi: 10.1007/s00104-023-01937-3. Online ahead of print.

ABSTRACT

BACKGROUND: Pseudomyxoma peritonei syndrome (PMP) is an orphan disease. Surgery is the fundament of treatment.

METHOD: Short review summarizing the state of the art treatment.

RESULTS: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) form the foundations of treatment for PMP. The peritoneal cancer index should be preoperatively determined based on imaging and/or laparoscopy, intraoperatively validated and both should be documented. An extraperitoneal surgical preparation technique leads to effective en bloc resection of the peritoneum and the affected abdominal area. The HIPEC technique should be performed with mitomycin C for 60-90 min. Complete CRS (CC = 0, CC = 1) and the histological subtype are relevant for the prognosis. Structured educational programs and mentoring can optimize the learning curve. The aftercare should be performed at the surgical center. After follow-up imaging at 3 months after CRS, in the first 2 years a control should be carried out every 6 months. Thereafter, the intervals can be extended to 1 year.

CONCLUSION: Standardized surgical treatment and HIPEC, optimized specific surgical training and structured follow-up at the center lead to an excellent long-term prognosis for patients with PMP.

PMID:37578542 | DOI:10.1007/s00104-023-01937-3

Expert Rev Respir Med. 2023 Aug 14. doi: 10.1080/17476348.2023.2247989. Online ahead of print.

ABSTRACT

INTRODUCTION: Pulmonary veno-occlusive disease (PVOD) is an orphan disease and uncommon etiology of pulmonary arterial hypertension (PAH) characterized by substantial small pulmonary vein and capillary involvement.

AREAS COVERED: PVOD, also known as 'PAH with features of venous/capillary involvement' in the current ESC/ERS classification.

EXPERT OPINION: In recent years, particular risk factors for PVOD have been recognized, including genetic susceptibilities and environmental factors (such as exposure to occupational organic solvents, chemotherapy, and potentially tobacco). The discovery of biallelic mutations in the EIF2AK4 gene as the cause of heritable PVOD has been a breakthrough in understanding the molecular basis of PVOD. Venous and capillary involvement (PVOD-like) has also been reported to be relatively common in connective tissue disease-associated PAH (especially systemic sclerosis), and in rare pulmonary diseases like sarcoidosis and pulmonary Langerhans cell granulomatosis. Although PVOD and pulmonary arterial hypertension (PAH) exhibit similarities, including severe precapillary PH, it is essential to differentiate between them since PVOD has a worse prognosis and requires specific management. Indeed, PVOD patients are characterized by poor response to PAH-approved drugs, which can lead to pulmonary edema and clinical deterioration. Due to the lack of effective treatments, early referral to a lung transplantation center is crucial.

PMID:37578057 | DOI:10.1080/17476348.2023.2247989

J Biomed Inform. 2023 Sep;145:104474. doi: 10.1016/j.jbi.2023.104474. Epub 2023 Aug 10.

ABSTRACT

Inferring knowledge from known relationships between drugs, proteins, genes, and diseases has great potential for clinical impact, such as predicting which existing drugs could be repurposed to treat rare diseases. Incorporating key biological context such as cell type or tissue of action into representations of extracted biomedical knowledge is essential for principled pharmacological discovery. Existing global, literature-derived knowledge graphs of interactions between drugs, proteins, genes, and diseases lack this essential information. In this study, we frame the task of associating biological context with protein-protein interactions extracted from text as a classification task using syntactic, semantic, and novel meta-discourse features. We introduce the Insider corpora, which are automatically generated PubMed-scale corpora for training classifiers for the context association task. These corpora are created by searching for precise syntactic cues of cell type and tissue relevancy to extracted regulatory relations. We report F1 scores of 0.955 and 0.862 for identifying relevant cell types and tissues, respectively, for our identified relations. By classifying with this framework, we demonstrate that the problem of context association can be addressed using intuitive, interpretable features. We demonstrate the potential of this approach to enrich text-derived knowledge bases with biological detail by incorporating cell type context into a protein-protein network for dengue fever.

PMID:37572825 | DOI:10.1016/j.jbi.2023.104474

Orphanet J Rare Dis. 2023 Aug 11;18(1):242. doi: 10.1186/s13023-023-02837-9.

ABSTRACT

BACKGROUND: A rare disease (RD) diagnosis and therapy can affect the family's quality of life and mental health. A lack of information and missing care options lead to helplessness and psychological stress within families. This work aims to identify patients' and parents' experiences in daily life and with the health care system as well as their needs and current pathways to psychosocial care to develop implementation strategies adapted to the families' needs.

METHODS: The present analysis is part of the national multicenter study "Children Affected by Rare Disease and Their Families-Network (CARE-FAM-NET)." We conducted semi-structured telephone interviews with children, adolescents, and young adults with RD (aged 12 to 21 years) and parents of children with RD (aged 0 to 17 years). We analyzed the transcribed and anonymized interviews using the method of focused interview analyses to identify previous experiences with medical and psychosocial care and possible needs for improvement and support.

RESULTS: Seventy-four parents of children with RD and 15 children, adolescents, and young adults with RD participated. Five main themes emerged. Daily life with an RD: RD affects the everyday and social life of the respondents, negatively impacting mental well-being. Experiences with the health care system: The long diagnostic path is stressful for families. Professionals' lack of information/education leads to inadequate care for those affected. Psychosocial support: Families do not know about psychosocial care services. In some cases, the families take advantage of psychosocial support services (such as support groups or advocacy groups), which are predominantly very helpful. Difficulties and barriers: Time, socio-legal and organizational problems burden families and lead to advantages in using psychosocial services. Improvements for patient-oriented support: Those affected wished for timely, preventive support (especially in administrative and socio-legal matters) and education regarding psychosocial care services.

CONCLUSION: RD represent a great challenge for all family members - patients, parents, and siblings. The patients' and parents' previous experiences in daily life, medical and psychosocial care show a need for target-group specific support, including training of health care professionals and low-threshold access care services and practical help for all family members.

PMID:37568186 | PMC:PMC10422846 | DOI:10.1186/s13023-023-02837-9

Orphanet J Rare Dis. 2023 Aug 11;18(1):241. doi: 10.1186/s13023-023-02850-y.

ABSTRACT

BACKGROUND: A rare muscle disease, GNE myopathy is caused by mutations in the GNE gene involved in sialic acid biosynthesis. Our recent phase II/III study has indicated that oral administration of aceneuramic acid to patients slows disease progression.

METHODS: We conducted a phase III, randomized, placebo-controlled, double-blind, parallel-group, multicenter study. Participants were assigned to receive an extended-release formulation of aceneuramic acid (SA-ER) or placebo. Changes in muscle strength and function over 48 weeks were compared between treatment groups using change in the upper extremity composite (UEC) score from baseline to Week 48 as the primary endpoint and the investigator-assessed efficacy rate as the key secondary endpoint. For safety, adverse events, vital signs, body weight, electrocardiogram, and clinical laboratory results were monitored.

RESULTS: A total of 14 patients were enrolled and given SA-ER (n = 10) or placebo (n = 4) tablets orally. Decrease in least square mean (LSM) change in UEC score at Week 48 with SA-ER (- 0.115 kg) was numerically smaller as compared with placebo (- 2.625 kg), with LSM difference (95% confidence interval) of 2.510 (- 1.720 to 6.740) kg. In addition, efficacy was higher with SA-ER as compared with placebo. No clinically significant adverse events or other safety concerns were observed.

CONCLUSIONS: The present study reproducibly showed a trend towards slowing of loss of muscle strength and function with orally administered SA-ER, indicating supplementation with sialic acid might be a promising replacement therapy for GNE myopathy.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT04671472).

PMID:37568154 | DOI:10.1186/s13023-023-02850-y

Orphanet J Rare Dis. 2023 Aug 10;18(1):240. doi: 10.1186/s13023-023-02847-7.

ABSTRACT

BACKGROUND: Genetic testing can facilitate the diagnosis and subsequent therapeutic management of rare diseases. However, there is a lack of data on the use of genetic testing for rare diseases. This study aims to describe the utilization rate and troubles encountered by clinicians in treating rare diseases with genetic testing.

METHODS: A cross-sectional electronic questionnaire survey was conducted between June and October 2022 among the medical staff from the hospitals covering all provinces, municipalities, and autonomous regions of China. The survey on genetic testing focused on whether genetic testing was used in the diagnosis and treatment of rare diseases, the specific methods of genetic testing, and the problems encountered when using genetic testing.

RESULTS: A total of 20,132 physicians who had treated rare diseases were included, of whom 35.5% were from the central region, 36.7% were from the eastern region, and 27.8% were from the western region. The total utilization rate of genetic testing for rare diseases was 76.0% (95%CI: 75.4-76.6). The use of genetic testing was highest in the Eastern region (79.2% [95% CI: 78.3-80.1]), followed by the Central (75.9% [95% CI: 74.9-76.9]) and Western regions (71.9% [95% CI: 70.7-73.1]). More than 90% (94.1% [95%CI: 93.4-94.8]) of pediatricians had used genetic testing to treat rare diseases, with surgeons having the lowest use of genetic testing (58.3% [95% CI: 56.6-60.0]). Physicians' departments and education levels affect the use of genetic testing. Most physicians have used a variety of genetic tests in the management of rare diseases, the most popular methods were "Whole-exome sequencing (Proband)" and "Whole-exome sequencing (families of three or more)". Doctors have encountered many problems with the use of genetic testing in the diagnosis and treatment of rare diseases, among which the high price was the main concern of medical workers.

CONCLUSION: Three-quarters of physicians used genetic testing in rare disease practice, and there were regional differences in the use of genetic testing. Recognition of the utilization of genetic testing can help identify patterns of resource utilization in different regions and provide a more comprehensive picture of the epidemiology of rare diseases in jurisdictions.

PMID:37563631 | PMC:PMC10416371 | DOI:10.1186/s13023-023-02847-7

Pediatr Ann. 2023 Aug;52(8):e282. doi: 10.3928/19382359-20230613-03. Epub 2023 Aug 1.

NO ABSTRACT

PMID:37561829 | DOI:10.3928/19382359-20230613-03

PLoS One. 2023 Aug 10;18(8):e0289921. doi: 10.1371/journal.pone.0289921. eCollection 2023.

ABSTRACT

BACKGROUND: Statistical analyses of clinical data are a cornerstone in understanding pathomechanisms of disorders. In rare disorders, cross-sectional datasets of sufficient size are usually not available. Taking AA amyloidosis as an example of a life-threatening rare disorder resulting from of uncontrolled chronic inflammation, we propose techniques from time series analysis to predict organ response to treatment. The advantage of time-series analysis is that it solely relies on temporal variation and therefore allows analyzing organ response to treatment even when the cross-sectional dimension is small.

METHODS: The joint temporal interdependence of inflammatory activity and organ response was modelled multivariately using vector autoregression (VAR) based on a unique 4.5 year spanning data set of routine laboratory, imaging data (e.g., 18F-Florbetaben-PET/CT) and functional investigations of a 68-year-old patient with multi-organ involvement of AA amyloidosis due to ongoing inflammatory activity of a malignant paraganglioma in stable disease for >20 years and excellent response to tocilizumab).

RESULTS: VAR analysis showed that alterations in inflammatory activity forecasted alkaline phosphatase (AP). AP levels, but not inflammatory activity at the previous measurement time point predicted proteinuria.

CONCLUSION: We demonstrate the feasibility and value of time series analysis for obtaining clinically reliable information when the rarity of a disease prevents conventional prognostic modelling approaches. We illustrate the comparative utility of blood, functional and imaging markers to monitor the development and regression of AA amyloidosis.

PMID:37561769 | PMC:PMC10414553 | DOI:10.1371/journal.pone.0289921

J Inherit Metab Dis. 2023 Sep;46(5):824-838. doi: 10.1002/jimd.12663.

ABSTRACT

Over the past decade high-throughput DNA sequencing approaches, namely whole exome and whole genome sequencing became a standard procedure in Mendelian disease diagnostics. Implementation of these technologies greatly facilitated diagnostics and shifted the analysis paradigm from variant identification to prioritisation and evaluation. The diagnostic rates vary widely depending on the cohort size, heterogeneity and disease and range from around 30% to 50% leaving the majority of patients undiagnosed. Advances in omics technologies and computational analysis provide an opportunity to increase these unfavourable rates by providing evidence for disease-causing variant validation and prioritisation. This review aims to provide an overview of the current application of several omics technologies including RNA-sequencing, proteomics, metabolomics and DNA-methylation profiling for diagnostics of rare genetic diseases in general and inborn errors of metabolism in particular.

PMID:37553850 | DOI:10.1002/jimd.12663

Orphanet J Rare Dis. 2023 Aug 9;18(1):236. doi: 10.1186/s13023-023-02839-7.

ABSTRACT

BACKGROUND: Rare diseases have become a major public health concern worldwide. However, detailed epidemiological data are lacking. With the development of the Internet, search queries have played an important role in disease surveillance. In this study, we explored a new method for the epidemiological research on rare diseases, using large-scale online search queries and reported case data. We distilled search logs related to rare diseases nationwide from 2016 to 2019. The case data were obtained from China's national database of rare diseases during the same period.

RESULTS: A total of 120 rare diseases were included in this study. From 2016 to 2019, the number of patients with rare diseases estimated using search data and those obtained from the case database showed an increasing trend. Rare diseases can be ranked by the number of search estimated patients and reported patients, and the rankings of each disease in both search and reported case data were generally stable. Furthermore, the disease rankings in the search data were relatively consistent with the reported case data in each year, with more than 50% of rare diseases having a ranking difference of -20 to 20 between the two systems. In addition, the relationship between the disease rankings in the two systems was generally stable over time. Based on the relationship between the disease rankings in the search and reported case data, rare diseases can be classified into two categories.

CONCLUSION: Online search queries may provide an important new resource for detecting rare diseases. Rare diseases can be classified into two categories to guide different epidemiological research strategies.

PMID:37559136 | PMC:PMC10411025 | DOI:10.1186/s13023-023-02839-7

G3 (Bethesda). 2023 Aug 9;13(8):jkad144. doi: 10.1093/g3journal/jkad144.

NO ABSTRACT

PMID:37556359 | PMC:PMC10411584 | DOI:10.1093/g3journal/jkad144

Genetics. 2023 Aug 9;224(4):iyad121. doi: 10.1093/genetics/iyad121.

NO ABSTRACT

PMID:37556311 | PMC:PMC10411596 | DOI:10.1093/genetics/iyad121

Hematology. 2023 Dec;28(1):2241226. doi: 10.1080/16078454.2023.2241226.

ABSTRACT

BACKGROUND: In China, conventional genetic testing methods can only detect common thalassemia variants. Accurate detection of rare thalassemia is crucial for clinical diagnosis, especially for children that need long-term blood transfusion. This study aims to explore the application value of third-generation sequencing (TGS) in the diagnosis of rare thalassemia in children with anemia.

METHODS: We enrolled 20 children with anemia, excluding from iron deficiency anemia (IDA). TGS was employed to identify both known and novel thalassemia genotypes, while sanger sequencing was used to confirm the novel mutation detected.

RESULTS: Among the 20 samples, we identified 5 cases of rare thalassemia. These included β-4.9 (hg38,Chr11:5226187-5231089) at HBB gene, α-91(HBA2:c.*91delT), αCD30(HBA2:c.91-93delGAG), Chinese Gγ+(Aγδβ)0(NG_000007.3: g .48795-127698 del 78904) and delta - 77(T > C)(HBD:c.-127T>C). Notably, the -SEA/α-91α genotype associated with severe non-deletional hemoglobin H disease (HbH disease) has not been previously reported. Patients with genotypes β654/β-4.9 and -SEA/α-91α necessitate long-term blood transfusions, and those with the -SEA/αCD30α, Chinese Gγ+(Aγδβ)0 and delta thalassemia demonstrate mild anemia.

CONCLUSIONS: TGS demonstrates promising potential as a diagnostic tool for suspected cases of rare thalassemia in children, especially those suspected to have transfusion-dependent thalassemia (TDT).

PMID:37548329 | DOI:10.1080/16078454.2023.2241226

Front Endocrinol (Lausanne). 2023 Jul 20;14:1211426. doi: 10.3389/fendo.2023.1211426. eCollection 2023.

ABSTRACT

X-linked hypophosphatemia (XLH) is a rare, progressive, genetic disease with multisystem impact that typically begins to manifest in early childhood. Two treatment options exist: oral phosphate in combination with active vitamin D ("conventional therapy") and a fully human monoclonal anti-FGF23 antibody, burosumab. The clinical benefit of conventional therapy in adults is limited, and poor tolerance and complications are common. Burosumab was first approved as a treatment for XLH in 2018 and its disease-modifying benefits in clinical trials in children suggest burosumab treatment could also alter the disease course in adults. Without long-term clinical data on multiple XLH-related sequelae available, the results of an elicitation exercise are reported, in which eight global experts in XLH posited how long-term treatment with burosumab is anticipated to impact the life course of clinical sequelae in adults with XLH. Based on their clinical experiences, the available evidence and their disease understanding, the experts agreed that some long-term benefits of using burosumab are likely in adults with XLH even if they have a misaligned skeleton from childhood. Burosumab treatment is anticipated to reduce the incidence of fractures and halt the progression of clinical sequelae associated with conventional therapy. While the trajectories for established dental abscesses are not expected to improve with burosumab treatment, dental abscess development may be prevented. Starting treatment with burosumab in childhood to increase the likelihood of an aligned skeleton and continuation into and throughout adulthood to maintain euphosphatemia may optimize patient outcomes, although future real-world investigation is required to support this hypothesis.

PMID:37547321 | PMC:PMC10400326 | DOI:10.3389/fendo.2023.1211426

J Allergy Clin Immunol Pract. 2023 Aug 4:S2213-2198(23)00815-2. doi: 10.1016/j.jaip.2023.07.042. Online ahead of print.

ABSTRACT

BACKGROUND: Debates on the allocation of medical resources during the COVID-19 pandemic revealed the need for a better understanding of immunologic risk. Studies highlighted variable clinical outcomes of SARS-CoV-2 infections in individuals with defects in both adaptive and innate immunity, suggesting additional contributions from other factors. Notably, none of these studies controlled for variables linked with social determinants of health.

OBJECTIVE: To determine the contributions of determinants of health to risk of hospitalization for SARS-CoV-2 infection among individuals with inborn errors of immunodeficiencies.

METHODS: This is a retrospective, single-center cohort study of 166 individuals with inborn errors of immunity, aged two months through 69 years, who developed SARS-CoV-2 infections from March 1, 2020 through March 31, 2022. Risks of hospitalization was assessed using a multivariable logistic regression analysis.

RESULTS: The risk of SARS-CoV-2-related hospitalization was associated with underrepresented racial and ethnic populations (odds ratio [OR] 4.50; confidence interval [CI], 1.57 - 13.4), a diagnosis of any genetically-defined immunodeficiency (OR 3.32; CI, 1.24 - 9.43), obesity (OR 4.24; CI, 1.38 - 13.3), and neurologic disease (OR 4.47; CI, 1.44 - 14.3. COVID-19 vaccination was associated with reduced hospitalization risk (OR 0.52; CI, 0.31 - 0.81). Defects in T cell and innate immune function, immune-mediated organ dysfunction, and social vulnerability were not associated with increased risk of hospitalization after controlling for covariates.

CONCLUSIONS: The associations between race, ethnicity, and obesity with increased risk of hospitalization for SARS-CoV-2 infection indicate the importance of variables linked with social determinants of health as immunologic risk factors for individuals with inborn errors of immunity.

PMID:37544429 | DOI:10.1016/j.jaip.2023.07.042

Am J Hum Genet. 2023 Aug 3;110(8):1229-1248. doi: 10.1016/j.ajhg.2023.06.009.

ABSTRACT

Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. Newer tests, such as short-read genome or RNA sequencing, can be challenging to order, and emerging technologies, such as optical genome mapping and long-read DNA sequencing, are not available clinically. Furthermore, there is no clear guidance on the next best steps after inconclusive evaluation. Here, we review why a clinical genetic evaluation may be negative, discuss questions to be asked in this setting, and provide a framework for further investigation, including the advantages and disadvantages of new approaches that are nascent in the clinical sphere. We present a guide for the next best steps after inconclusive molecular testing based upon phenotype and prior evaluation, including when to consider referral to research consortia focused on elucidating the underlying cause of rare unsolved genetic disorders.

PMID:37541186 | DOI:10.1016/j.ajhg.2023.06.009

J Glob Health. 2023 Aug 4;13:04030. doi: 10.7189/jogh.13.04030.

ABSTRACT

BACKGROUND: Individuals with rare diseases (RD) have been historically understudied. Previous publications reported that existing primary health care (PHC) workforces and associated infrastructure had been shown to improve their access and health-related outcomes in low- and middle-income countries (LMICs). As current evidence about the impact of PHC on patients diagnosed with RD is yet highly dispersed, this scoping review aimed to collate available evidence of the impact of PHC on patients with RD and summarize published information from multiple stakeholders about the perceived usefulness and barriers to effective use of the PHC system.

METHODS: We searched Embase, Health System Evidence, PubMed, LILACS / BVS, and The Cochrane Library, from inception to September 1, 2022, for publications providing clear expert- or experience-based insights or data from patients living with RD at the PHC level of care. We included publications highlighting barriers to integrated care of patients with RD, reported by multiple social actors involved in caring for patients with RD. Two investigators screened publications, extracted data, and clustered information among records deemed eligible for inclusion. Data synthesis was performed using narrative and thematic-based analysis. Major findings identified and coded through a semantic-driven analysis were processed in vosViewer software and reported using descriptive statistics.

FINDINGS: Eighty publications were included in this review. Quali-quantitative analyses evidenced that the PHC level is essential for approaching patients with RD, mainly due to its longitudinal, multidisciplinary, and coordinated care delivery. In addition, several publications highlighted that the medical curriculum is inappropriate for preparing health care providers to deal with patients presenting unusual signs and symptoms and being diagnosed with RD. PHC teams are essential in orienting patients and families on emergency events. Technology-related concepts were reported in 19 publications, emphasizing their effectiveness on early diagnosis, optimal treatment definition, improvement of quality of life, and long-lasting follow-up.

CONCLUSIONS: We provided valuable information on the effectiveness of the PHC in fostering a creative, integrative, and supportive environment for patients living with RD. Our results can be helpful to several stakeholders in deciding what actions are still pending to achieve a solid and positive experience for patients with RD in the PHC.

REGISTRATION: PROSPERO (CRD42022332347).

PMID:37539555 | PMC:PMC10401310 | DOI:10.7189/jogh.13.04030

Orphanet J Rare Dis. 2023 Aug 3;18(1):229. doi: 10.1186/s13023-023-02845-9.

ABSTRACT

Drug development is a complex, resource intensive and long process in any disease area, and developing medicines to treat rare diseases presents even more challenges due to the small patient populations, often limited disease knowledge, heterogeneous clinical manifestations, and disease progression. However, common to all drug development programs is the need to gather as much information as possible on both the disease and the patients' needs ahead of the development path definition. Here, we propose a checklist named START, a tool that provides an overview of the key pillars to be considered when starting an orphan drug development: STakeholder mapping, Available information on the disease, Resources, and Target patient value profile. This tool helps to build solid foundations of a successful patient-centered medicines development program and guides different types of developers through a set of questions to ask for guidance through the starting phase of a rare disease therapeutic pathway.

PMID:37537670 | PMC:PMC10398909 | DOI:10.1186/s13023-023-02845-9

Seizure. 2023 Jul 30;111:56-57. doi: 10.1016/j.seizure.2023.07.023. Online ahead of print.

NO ABSTRACT

PMID:37536151 | DOI:10.1016/j.seizure.2023.07.023

Orphanet J Rare Dis. 2023 Aug 2;18(1):224. doi: 10.1186/s13023-023-02813-3.

ABSTRACT

Developing drugs for rare diseases is challenging, and the precision and objectivity of outcome measures is critical to this process. In recent years, a number of technologies have increasingly been used for remote monitoring of patient health. We report a systematic literature review that aims to summarize the current state of progress with regard to the use of digital outcome measures for real-life motor function assessment of patients with rare neurological diseases. Our search of published literature identified 3826 records, of which 139 were included across 27 different diseases. This review shows that use of digital outcome measures for motor function outside a clinical setting is feasible and employed in a broad range of diseases, although we found few outcome measures that have been robustly validated and adopted as endpoints in clinical trials. Future research should focus on validation of devices, variables, and algorithms to allow for regulatory qualification and widespread adoption.

PMID:37533072 | PMC:PMC10398976 | DOI:10.1186/s13023-023-02813-3