Orphanet J Rare Dis. 2025 Jul 16;20(1):365. doi: 10.1186/s13023-025-03875-1.

ABSTRACT

BACKGROUND: Rare bone diseases (RBDs) are an important group of conditions characterized by abnormalities in bone and cartilage. Their large number, individual rarity, and heterogeneity make accurate and timely diagnosis challenging. Establishing correlations between genotype and phenotype (mainly via imaging) is critical for diagnosing RBDs. Image recognition artificial intelligence (AI) has the potential to significantly improve the diagnostic process by assisting healthcare providers to identify and differentiate imaging patterns associated with various RBDs. This survey study sought to assess the interest of various healthcare providers worldwide in utilizing an AI-based assistant tool for the differential diagnosis of RBDs.

METHOD: Survey data were collected from March to September 2024. The survey was performed online and the link was disseminated via direct email, newsletters, and flyers at scientific talks and conferences.

RESULTS: We received 103 completed surveys, representing respondents from 27 different countries covering most global regions, but mostly from Europe, the United States, and Canada. The majority of the participants are physicians (n = 92, 89%) and primarily work at academic medical centers (n = 84, 81%). While each participant could select multiple specialties, the most frequent clinician types were medical geneticists, pediatricians, and endocrinologists, accounting for 71 (69%) of the respondents. Ninety-four (91%) of the respondents find imaging to be very or extremely important, and the majority (n = 84, 81%) consider X-rays to be the most important imaging modality. Although around half of the participants (n = 45) have concerns about AI-related errors and consider the explainability of AI algorithms to be very (42/103) or extremely (9/103) important, 81% of the respondents report that they are somewhat (n = 39) or extremely (n = 45) likely to consider integrating image recognition AI into their current diagnostic workflow.

CONCLUSIONS: Most survey participants are open to integrating image recognition AI into their RBD diagnostic workflow. However, concerns about AI-related errors, privacy, and model interpretability highlight the importance of transparent collaboration between developers and healthcare professionals throughout the development process to ensure that such technologies are clinically trustworthy and practically adoptable.

PMID:40671115 | DOI:10.1186/s13023-025-03875-1

Brief Bioinform. 2025 Jul 2;26(4):bbaf329. doi: 10.1093/bib/bbaf329.

ABSTRACT

Precision medicine tailors medical procedures to individual genetic overviews and offers transformative solutions for rare genetic conditions. Machine learning (ML) has enhanced genome-based precision medicine (GBPM) by enabling accurate diagnoses, customized treatments, and risk assessments. ML tools, including deep learning and ensemble methods, process high-dimensional genomic data and reveal discoveries in rare diseases. This review analyzes the ML applications in GBPM, emphasizing its role in disease classification, therapeutic optimization, and biomarker discovery. Key challenges, such as computational complexity, data scarcity, and ethical concerns, are discussed alongside advancements such as hybrid ML models and real-time genomic analysis. Security issues, including data breaches and ethical challenges, are addressed. This review identifies future directions, emphasizing the need for comprehensible ML models, increasing data-sharing frameworks, and global collaborations. By integrating the current research, this study provides a comprehensive perspective on the use of ML for rare genetic disorders, paving the way for transformative advancements in precision medicine.

PMID:40668553 | DOI:10.1093/bib/bbaf329

Orphanet J Rare Dis. 2025 Jul 16;20(1):363. doi: 10.1186/s13023-025-03892-0.

ABSTRACT

Therapeutic development for rare diseases is difficult for pharmaceutical companies due to significant scientific challenges, extensive costs, and low financial returns. It is increasingly common for caregivers and patient advocacy groups to partner with biomedical professionals to finance and develop treatments for rare diseases. This case study illustrates the story of Terry Pirovolakis, a father who partnered with biomedical professionals to develop the novel gene therapy, Melpida, within 36 months of the diagnosis of his infant son. We identify the factors that led to the success of Melpida and analyze the business model of Elpida Therapeutics, a social purpose corporation founded by Pirovolakis to reproduce the success of Melpida for other rare diseases. We conclude with four lessons from Melpida to inform caregivers like Pirovolakis on developing novel gene therapies to save their loved ones.

PMID:40665386 | DOI:10.1186/s13023-025-03892-0

Neurol Genet. 2025 Jul 3;11(4):e200277. doi: 10.1212/NXG.0000000000200277. eCollection 2025 Aug.

ABSTRACT

BACKGROUND AND OBJECTIVES: Nemaline myopathy (NM) is a congenital myopathy with a wide severity spectrum, from severe, generalized muscle weakness and respiratory failure in the neonatal period to mild, distal weakness in young adulthood. Eleven genes have been definitively established to cause the condition. Although some recurrent variants have been identified, the overall correlation of genotype with clinical severity in NM remains poor. This poses challenges when counseling families about prognosis after a diagnosis of NM is made. Better clinical and molecular predictors of outcome are needed for clinical trial readiness.

METHODS: A retrospective cohort analysis of 275 patients with a histopathologic diagnosis of NM and/or pathogenic variants in NM-associated genes was performed to identify relationships between early clinical findings and long-term outcomes, including need for respiratory and feeding support.

RESULTS: Early clinical predictors of long-term outcomes were identified: patients with hypotonia at birth had increased odds of requiring gastrostomy tubes, and patients with respiratory distress at birth had increased odds of requiring both gastrostomy tubes and invasive ventilation. Individuals with ACTA1-NM were more likely to require feeding tubes and invasive ventilation in the first year of life compared with those with NEB-related NM, but the odds of requiring invasive ventilation were similar after the first year of age. Additional clinical information is presented by genotype and severity class.

DISCUSSION: Neonatal findings of individuals with NM are correlated with long-term clinical outcomes, and there are some relationships between genotype and disease severity. Prospective longitudinal studies are needed to confirm these findings and evaluate for additional early clinical predictors of prognosis.

PMID:40661861 | PMC:PMC12258819 | DOI:10.1212/NXG.0000000000200277

Neurosci Res. 2025 Jul 11:104940. doi: 10.1016/j.neures.2025.104940. Online ahead of print.

ABSTRACT

This study assessed whether asfotase alfa treatment in Akp2-/- mice (a model of hypophosphatasia) reversibly normalizes GABA and cystathionine in brain tissue to concentrations in wild-type mice. To do this metabolite concentrations were analyzed at postnatal days 10 and 48. The data showed that asfotase alfa treatment significantly increased GABA concentrations and significantly decreased cystathionine concentrations in Akp2-/- mice compared with vehicle-treated Akp2-/- mice (GABA: 1.28±0.03 vs 0.48±0.02 μmol/g [P<0.0001]; cystathionine: 0.06±0.00 vs 0.60±0.02 μmol/g [P<0.0001]). Concentrations post-treatment were similar to those in wild-type mice. Asfotase alfa withdrawal negated these effects. These analyses demonstrated that asfotase alfa restores GABA and cystathionine concentrations in a murine model of hypophosphatasia.

PMID:40653050 | DOI:10.1016/j.neures.2025.104940

Int J Mol Sci. 2025 Jun 26;26(13):6126. doi: 10.3390/ijms26136126.

ABSTRACT

Recent diagnostic advances reveal that lymphatic disease in Noonan syndrome (NS) and other NS-like RASopathies often stems from central conducting lymphatic anomalies (CCLAs). The RAS/MAPK-ERK pathway plays a central role in lymphangiogenesis. Targeting this pathway with MEK-inhibitor trametinib has emerged as a promising therapeutic strategy for managing CCLAs in patients with NS-like RASopathies. This case series assessed the clinical outcomes of trametinib therapy in eight patients with NS-like RASopathies and CCLA, each offering unique insights into the therapeutic efficacy of MEK inhibition. In infants, a lower dose of 0.01 mg/kg/day and earlier discontinuation of trametinib therapy effectively alleviated the symptoms of congenital chylothorax and rescued the lymphatic phenotype, compared to similar published cases. Moreover, four patients aged >11 y showed a slower response and did not achieve complete symptomatic recovery. In conclusion, it is advised to consider trametinib therapy for patients with severe, therapy-refractory CCLA in patients with NS-like RASopathies. However, individual responses to trametinib therapy may vary, with some patients demonstrating more favorable outcomes than others. Further investigation into potential enhancers and suppressors of the lymphatic phenotype is necessary for more accurate treatment predictions. While these factors are likely genetic, we cannot rule out other intrinsic or physiological factors.

PMID:40649904 | DOI:10.3390/ijms26136126

Int J Mol Sci. 2025 Jun 24;26(13):6069. doi: 10.3390/ijms26136069.

ABSTRACT

Zebrafish is a well-recognized model for studying human genetic disorders. Recently, we proposed the homozygous cdkl5sa21938 mutant zebrafish as a model of CDKL5 deficiency disorder (CDD), a developmental epileptic encephalopathy with diverse symptoms. This study aimed to explore Cdkl5-associated molecular mechanisms in zebrafish and assess their similarity to those in mammals. We conducted RNA sequencing on whole cdkl5-/- zebrafish and wild-type siblings at 5 and 35 days post-fertilization (dpf) to compare their gene expression profiles. Most significant differentially expressed genes (DEGs) were related to muscle, neuronal, and visual systems which are affected in CDD. Gene Ontology analysis revealed downregulated DEGs enriched in muscle development, extracellular matrix, and actin cytoskeleton functions at both stages, while upregulated DEGs were enriched in eye development functions at 35 dpf. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed enrichment of downregulated DEGs in focal adhesion and extracellular matrix (ECM)-receptor interaction pathways at both stages. Neuronal development DEGs were mainly downregulated at both stages, while synaptic signaling DEGs were upregulated at 35 dpf. Crossing cdkl5-/- mutants with the Hb9:GFP transgenic line showed fewer motor neuron cells with shorter axons compared to the wild type, which may explain the impaired motor phenotype observed in zebrafish and CDD patients. Moreover, we identified key downregulated DEGs related to cartilage development at both stages and bone development at 35 dpf, potentially explaining the skeletal defects seen in zebrafish and CDD individuals. In conclusion, Cdkl5 loss in zebrafish leads to dysregulation of genes involved in CDKL5-associated functions in mammals, providing new insights into its less studied functions and phenotypes.

PMID:40649845 | DOI:10.3390/ijms26136069

Int J Mol Sci. 2025 Jun 23;26(13):6024. doi: 10.3390/ijms26136024.

ABSTRACT

Rare genetic movement disorders usually manifest early in life with dystonia, parkinsonism, chorea, or a combination thereof. These are often associated with neurodevelopmental delay, intellectual disability, speech problems, retinal abnormalities, seizures, ataxia, spasticity, or systemic features. Due to their vast number and pheno-genotypic heterogeneity, the diagnosis of these disorders can be challenging. However, recognising their core motor phenomenology as well as clinical, laboratory, and neuroradiological clues can expedite appropriate diagnostic workup, molecular diagnosis, and adequate treatment. In this review, we outline diagnostic clues to rare movement disorders (RMDs), focusing on those that present mainly with dystonia, parkinsonism, or paroxysmal dyskinesia due to genetic causes. Additionally, we provide a decision tree approach linking clinical, genetic, and imaging testing. Finally, we highlight selected RMDs that should not be missed, as they possess established treatments that can hinder their progression, prevent irreversible or life-threatening sequelae and, in certain cases, lead to complete symptom remission.

PMID:40649801 | DOI:10.3390/ijms26136024

Sci Rep. 2025 Jul 8;15(1):24442. doi: 10.1038/s41598-025-09744-y.

ABSTRACT

Following a confirmed genetic diagnosis, rare disease patients and their families encounter significant challenges in accessing diagnostic information and support. Patients and non-specialists are increasingly expected to interpret and share test results; however, existing standards are primarily designed for specialists. These standards fail to address the needs of resource-limited populations where low genomic literacy hampers accurate dissemination of genetic results. This research introduces RareInsight, an open-source, interactive dashboard designed to enhance the accessibility, comprehension, and collaboration of genetic data among patients, caregivers, clinicians, and researchers. Developed using shinydashboard, RareInsight was evaluated using whole exome sequencing data from skeletal dysplasia patients. It allows users to input and view Variant Call Format files and includes a searchable ClinVar variant table with filtering options, providing access to multiple resources based on search terms. RareInsight aims to simplify the dissemination of complex genetic information beyond the clinical setting. This dashboard serves as a pilot study demonstrating the potential of patient-centered interactive dashboards for the rare disease community.

PMID:40628872 | DOI:10.1038/s41598-025-09744-y

Orphanet J Rare Dis. 2025 Jul 7;20(1):344. doi: 10.1186/s13023-025-03879-x.

ABSTRACT

BACKGROUND: The cumulative economic burden of rare diseases surpasses that of common conditions, yet patterns of healthcare resource utilization (HRU) across rare diseases remain poorly characterized. This study leverages multimodal data collected during clinical care and through surveys to provide an in-depth evaluation of HRU across the disease journey of individuals with rare genetic diseases. Individuals with a confirmed diagnosis of Kleefstra syndrome (KS; n = 40) or SLC6A1 epileptic encephalopathy (SLC6A1; n = 30) were recruited. Structured and unstructured data were abstracted from participants' medical records. Encounters per person-year of follow-up were calculated and compared pre- and post-diagnosis. Parents/guardians completed surveys assessing the impact of the participant's diagnosis on their care.

RESULTS: Records were available for a median of 6.4 years of follow-up from 268 unique healthcare facilities (median per patient = 4.5 facilities). Numbers of healthcare encounters were not significantly different 1 year pre- and post-diagnosis for either condition; however, the proportion of specialty encounters pre- and post-diagnosis varied significantly. Genetics encounters decreased for both conditions post-diagnosis. Cardiology, sleep medicine, and radiology encounters increased in KS post-diagnosis; conversely, audiology encounters decreased in KS post-diagnosis, and radiology encounters decreased in SLC6A1 post-diagnosis. Among specialty encounter types assessed, general practitioner (e.g. primary care, including pediatrics) encounters were the most common type for KS participants and the second-most common for SLC6A1 participants (after neurology encounters) both 1 year pre- and post-diagnosis. The number of both echocardiograms and electrocardiograms (ECG) significantly increased in KS 1 year post-diagnosis. 68% of survey respondents indicated that the participant's care changed post-diagnosis.

CONCLUSIONS: Though there was no significant difference in the number of encounters pre- and post-diagnosis, significant changes in types of HRU suggest that diagnosis leads to more appropriate care and treatment. Advocacy organizations, researchers, drug developers, payors, and policymakers should consider the value of an early diagnosis to improve long-term outcomes and quality of life for patients and invest in measures that will shorten the time to diagnosis accordingly.

PMID:40624551 | DOI:10.1186/s13023-025-03879-x

Cir Cir. 2025 Jul 4. doi: 10.24875/CIRU.24000236. Online ahead of print.

ABSTRACT

OBJECTIVE: Skeletal muscle ion channelopathies are a rare genetically inherited orphan disease. Due to the unique characteristics of the symptoms of the disease, misdiagnosis of patients leads to irreversible losses. This study aims to raise awareness on this issue.

METHODS: 35 patients with a definitive diagnosis of skeletal muscle ion channelopathy were included in the study. The diagnoses of all patients were confirmed by gene analysis. Demographic and clinical characteristics of the patients were examined. After a definitive diagnosis was made, mimic symptoms and misdiagnoses were evaluated separately.

RESULTS: It was determined that 30 of the patients included in the study had multiple different diagnoses until they got the correct diagnosis. It is thought that due to delayed diagnosis or misdiagnosis, patients experience physical and mental loss, are exposed to ineffective drugs, and their daily lives are adversely affected, as well as serious cost losses.

CONCLUSIONS: It is stated that the names of misdiagnoses for imitation symptoms have changed with aging, and drug treatments are applied for each diagnosis. It is stated that health authorities should pay attention to this situation to reduce this.

PMID:40614251 | DOI:10.24875/CIRU.24000236

Echocardiography. 2025 Jul;42(7):e70225. doi: 10.1111/echo.70225.

ABSTRACT

We present a case of a primary cardiac synovial sarcoma, surrounding the right coronary artery and leaded to accelerate the blood flow of the tricuspid valve orifice.

PMID:40614057 | DOI:10.1111/echo.70225

BMC Nephrol. 2025 Jul 3;26(1):346. doi: 10.1186/s12882-025-04271-4.

ABSTRACT

BACKGROUND: Estimating disease epidemiology using health insurance claims data is challenging due to the lack of specific diagnostic codes. This study demonstrates an approach to estimate the epidemiology of primary immunoglobulin A nephropathy (IgAN) using German Statutory Health Insurance (SHI) claims data.

METHODS: A retrospective observational study was conducted using data from January 1st, 2015 to December 31st, 2022. Two coding algorithms - one restrictive and one inclusive - were developed to identify primary IgAN cases based on ICD-10-GM codes. The restrictive algorithm identified cases based on histologically confirmed diagnoses, while the inclusive algorithm included a broader range of related diagnoses. Annual incidence and prevalence rates were calculated and extrapolated to the German population.

RESULTS: The mean prevalence rate from 2017-2022 ranged from 4.5 (restrictive codes) to 38.3 (inclusive codes) cases per 100,000 individuals, demonstrating the orphan nature of primary IgAN. Mean incidence rates ranged from 0.2 to 0.6 cases per 100,000 individuals. In 2022, this corresponded to an estimated 4,043 to 32,229 prevalent cases and 164 to 538 incident cases in Germany.

CONCLUSION: This study presents an approach for estimating disease epidemiology in the absence of specific diagnostic codes, using primary IgAN as an example. While our dual-algorithm method provides valuable insights into the incidence and prevalence of primary IgAN in Germany, it also highlights the need for consistent coding practices and specific diagnostic codes for accurate epidemiological assessments.

PMID:40610969 | DOI:10.1186/s12882-025-04271-4

Sci Rep. 2025 Jul 3;15(1):23780. doi: 10.1038/s41598-025-04428-z.

ABSTRACT

In the time of advancing medical technology, there is a critical issue concerning the misdiagnosis of diseases. The aim of this research is to significantly reduce the occurrence of misdiagnoses in medical practice by leveraging hypergraphs and genomic data to improve diagnostic accuracy. We have designed and implemented a sophisticated computational framework for phenotype-driven disease prediction that leverages hypergraphs and genomic data to enhance the accuracy of disease identification, leading to more precise and timely treatments for patients. The study employed robust ranking algorithms, on a sample of 2130 diseases, 4655 genes and 9541 phenotypes collected from reliable sources of Orphanet and Human Phenotype Ontology (HPO) database to achieve highly favorable outcomes. The proposed method outperforms existing state-of-the-art tools such as Phenomizer and GCN, in terms of both prediction accuracy and processing speed. Notably, it captures 50% of causal genes within the top 10 predictions and 85% within the top 100 predictions and the algorithm maintains a high accuracy rate of 98.09% for the top-ranked gene. In conclusion, our study demonstrated the effectiveness of robust ranking algorithms and hypergraph framework in achieving accurate and reliable results for disease diagnosis. While the study provides valuable insights, it is important to note its limitations, such as the sample size and scope of diseases considered. Future research could explore the integration of additional data sources and refinement of algorithms to further enhance diagnostic capabilities. Overall, this study underscores the potential of algorithmic hypergraph based approaches in advancing medical diagnostics and improving healthcare delivery.

PMID:40610497 | DOI:10.1038/s41598-025-04428-z

Epidemiol Prev. 2025 Mar-Jun;49(2-3):181-189. doi: 10.19191/EP25.2-3.A776.025.

ABSTRACT

OBJECTIVES: to provide the epidemiological framework of those affected by rare diseases resident in the Campania Region (Southern Italy), using the data entered in the Campania Region Rare Disease Registry, acquiring information potentially useful for regional planning.

DESIGN: observational retrospective cohort study on patients with rare diseases included in the Regione Campania Rare Disease Registry from 01.01.2022 to 31.12.2022.

SETTING AND PARTICIPANTS: population included in the Rare Disease Registry and resident in the Campania Region as at 31.12.2022.

MAIN OUTCOME MEASURES: using the data entered in the Regione Campania Rare Disease Registry, the cumulative incidence (I) of patients with rare diseases resident in Campania was calculated, stratified by age group and rare disease group with the respective 95% confidence intervals (IC95%). Standardised cumulative provincial incidences were also calculated. These are reported using a multiplication factor of 100,000.

RESULTS: the incidence of patients with rare diseases in the Campania Region is 50.0 (IC95% 49.4-50.6) per 100,000 inhabitants in the year 2022. Furthermore, the rare disease groups with the highest incidence per 100,000 inhabitants are diseases of the central and peripheral nervous system (I: 8.32 per 100,000 inhabitants) and congenital malformations, chromosomopathies and genetic syndromes (I: 8.52 per 100,000 inhabitants). Moreover, the age groups in which the incidence is highest are in the paediatric age group.

CONCLUSIONS: an epidemiological framework of the Campania Region on rare diseases such as this one for the year 2022 is fundamental for national and regional planning in order to improve the care and quality of life of people affected by rare diseases, who often feel neglected by society. Sharing this type of information also draws attention to the need for faster diagnosis and the specialisation of new centres.

PMID:40605728 | DOI:10.19191/EP25.2-3.A776.025

Nature. 2025 Jul;643(8070):47-59. doi: 10.1038/s41586-025-09096-7. Epub 2025 Jul 2.

ABSTRACT

From fertilization onwards, the cells of the human body acquire variations in their DNA sequence, known as somatic mutations. These postzygotic mutations arise from intrinsic errors in DNA replication and repair, as well as from exposure to mutagens. Somatic mutations have been implicated in some diseases, but a fundamental understanding of the frequency, type and patterns of mutations across healthy human tissues has been limited. This is primarily due to the small proportion of cells harbouring specific somatic variants within an individual, making them more challenging to detect than inherited variants. Here we describe the Somatic Mosaicism across Human Tissues Network, which aims to create a reference catalogue of somatic mutations and their clonal patterns across 19 different tissue sites from 150 non-diseased donors and develop new technologies and computational tools to detect somatic mutations and assess their phenotypic consequences, including clonal expansions. This strategy enables a comprehensive examination of the mutational landscape across the human body, and provides a comparison baseline for somatic mutation in diseases. This will lead to a deep understanding of somatic mutations and clonal expansions across the lifespan, as well as their roles in health, in ageing and, by comparison, in diseases.

PMID:40604182 | DOI:10.1038/s41586-025-09096-7

ACS Nano. 2025 Jul 2. doi: 10.1021/acsnano.5c05498. Online ahead of print.

ABSTRACT

Globoid cell leukodystrophy (GLD) is a rare hereditary inborn error of metabolism due to recessive mutations that cause loss of function of the enzyme galactosylceramidase (GALC). This results in the accumulation of the sphingolipids galactosylceramide (GalCer) and galactosylsphingosine (GalSph) in the lysosomes of neuronal cells. The accumulated GalCer and GalSph in cerebral macrophages of GLD patients are neurotoxic to oligodendrocytes and Schwann cells, leading to demyelination in the nervous system. The disease typically presents with infantile onset in the first six months of life and death by age 2. Here, we identified a supramolecular structure of GalCer and GalSph that may contribute to GLD pathology. Using biophysical assays commonly used for studying proteinaceous amyloids, e.g., amyloid-specific dyes, microscopical imaging, and a series of analytical methods (FTIR, PXRD, and SAXS), we demonstrate that both GalCer and GalSph can self-assemble in vitro into highly organized fibrils reminiscent of fibrils of amyloidogenic proteins. These fibrils exhibit significant cytotoxicity to both neuronal and oligodendroglial cells. Using an inhibitor of the GALC enzyme in cell culture to mimic the GLD pathophysiology, we could detect the accumulation of these fibrils in cells. We also observed that small molecules, which are bona fide inhibitors of proteinaceous amyloids, effectively mitigated the formation of the GalCer and GalSph fibrillar structures in vitro. Finally, the small molecule ameliorated the cytotoxic effects of the sphingolipid fibrils in SH-SY5Y cells, suggesting a potential avenue for therapeutic intervention in GLD orphan disease.

PMID:40603002 | DOI:10.1021/acsnano.5c05498

Am J Hematol. 2025 Jul 2. doi: 10.1002/ajh.27739. Online ahead of print.

NO ABSTRACT

PMID:40600615 | DOI:10.1002/ajh.27739

Orphanet J Rare Dis. 2025 Jul 1;20(1):321. doi: 10.1186/s13023-025-03838-6.

ABSTRACT

BACKGROUND: Rare diseases affect small populations but present unique challenges in access to healthcare and social support. The needs of patients and their caregivers extend beyond medical treatments, impacting various aspects of their lives. This study provides a narrative overview of these diverse needs experienced by patients and caregivers.

METHODS: A rapid literature review was conducted in PubMed and Embase, including studies assessing needs in rare diseases. Following Cochrane guidelines, two researchers screened 1.419 articles (74%) double-blinded, followed by a single researcher screening the remaining 509 articles (26%). Two researchers collaboratively extracted data into an extraction table. To validate and complement these findings, two stakeholder consultations were held with representatives from patient organisations, healthcare providers, the pharmaceutical industry, and policymakers.

RESULTS: A total of 272 articles were included in the review, and respectively 25 and 33 participants participated in the consultations. The identified needs were categorized into two levels: (i) patient needs, and (ii) caregiver needs, along with one overarching transversal need: (iii) information needs. Patient needs spanned health, healthcare, and social dimensions. Psychological, mental, and emotional health were frequently highlighted, but also autonomy emerged as a significant need. Healthcare needs included gaps in timely and accurate diagnoses, underscoring the need for more awareness among healthcare providers and appropriate diagnostic tools. Coordinated multidisciplinary care and accessibility to care and treatments were also identified as essential, yet lacking. Socially, patients experienced unmet needs in support networks, workplace inclusion, education, and financial stability. Caregivers' needs were related to physical and mental health, social connection, and financial support. Information needs, affecting both levels and even extending to healthcare providers, underscored the demand for more comprehensive, accessible information on rare diseases, treatment options, healthcare services, and available social support.

CONCLUSION: This study underscores the complex needs of persons living with rare diseases and their caregivers, advocating for a holistic approach in healthcare policy. Beyond medical interventions, addressing timely diagnosis, coordinated care, and psychological support are essential. Policymakers must consider these multifaceted needs to enhance patient outcomes and foster an inclusive, patient-centred healthcare framework.

PMID:40598354 | DOI:10.1186/s13023-025-03838-6

Orphanet J Rare Dis. 2025 Jul 1;20(1):331. doi: 10.1186/s13023-025-03862-6.

ABSTRACT

BACKGROUND: Melorheostosis is a rare skeletal and connective tissue disorder with the estimated prevalence of 1/1,100,000. Low prevalence of rare diseases (RDs) can lead to suboptimal knowledge and expertise among clinicians.

METHODS: The European Registries for Rare Endocrine and Bone Conditions (EuRREB) facilitates collection of a set of Core Data Elements and a specific dataset within the 'condition specific module' of the Core Registry platform. The Rare Bone Disease Action Group of the European Calcified Tissue Society (ECTS) collaborated with ERN BOND to develop a specific dataset for Melorheostosis.

RESULTS: An initial dataset was shortened to 44 unique variables. In January 2023, the Melorheostosis condition specific module was published and now consists of 18 patients from 2 countries. The median age of patients was 49 years old (range 23-82) and female to male ratio was 15:3 (83.3%). Family history of Melorheostosis was negative for all patients. The most affected bones were lower limbs in 12 cases (66.7%). Specifically, spine, feet and ribs were involved each in 2 cases (11%), skull and pelvis-in one patient each (5.5%). Two patients (11%) suffered from more than 1 lesion. Hyperostosis was present in 3 patients (16.7%), skeletal deformity-in 6 (33%), joint stiffness - in 11 (61%), asymmetry-in 16 (88.9%), joint limitation-in 12 (66.7%) patients. Swelling and muscle atrophy were reported in 1 case each (5.5%), vascular abnormalities-in 2 cases (11%), skin abnormality in 1 case (5.5%). Pain was present in 14 from 18 patients (77.8%). Genetic testing was performed in 5 patients (27.7%).

CONCLUSION: A condition specific module, for Melorheostosis, within an established registry has been developed. This will serve a useful resource to inform clinicians about this rare disease, and can support several healthcare initiatives such as guidelines creation and healthcare improvement strategies.

PMID:40598201 | DOI:10.1186/s13023-025-03862-6