Orphanet J Rare Dis. 2025 May 28;20(1):258. doi: 10.1186/s13023-025-03754-9.

ABSTRACT

INTRODUCTION: In Thailand, obtaining medicines for rare diseases presents significant challenges, with limited evidence highlighting these issues.

OBJECTIVES: To evaluate the accessibility of medicines and the extent of health insurance coverage for treatments of rare diseases in Thailand.

METHOD: This study utilized a thorough review of current health policies, drug registration database, and insurance coverage conditions. Additionally, procurement data from the Ministry of Finance was analyzed to verify the acquisition of medicines intended for the treatment of rare diseases.

RESULTS: A review of the availability and procurement of medicines for rare diseases in Thailand revealed considerable limitations in both registration and accessibility. According to the International Rare Diseases Research Consortium, only 46.80% of their recommended medicines were registered in Thailand, and of these, just 22.93% were included in the national essential medicines list. Additionally, a review of the state's pharmaceutical procurement dataset over the past 5 years showed that merely 31.70% of these registered drugs had been purchased from suppliers for use in hospitals.

CONCLUSION: To address these issues, the study recommended accelerating the approval process for rare disease medicines, expanding health insurance coverage, establishing financial support for patients, and creating a specific pricing policy for orphan drugs. Collaborative efforts among stakeholders were emphasized as crucial for improving access to essential medicines and enhancing treatment outcomes for patients with rare diseases in Thailand.

PMID:40437602 | DOI:10.1186/s13023-025-03754-9

Genes (Basel). 2025 Apr 29;16(5):522. doi: 10.3390/genes16050522.

ABSTRACT

BACKGROUND/OBJECTIVES: Genodermatoses are genetic conditions with clinical symptoms manifesting in the skin and adjoining tissues, individually rare but comprising a large and heterogeneous group of disorders that represents 15% of genetic diseases. This article discusses the results of individuals with genodermatoses from a reference center for rare diseases studied through whole genome sequencing conducted by the Brazilian Rare Genomes Project between 2021 and 2023.

METHODS: A retrospective case series with data comprising sex, age at first assessment in the hospital, family history, clinical findings, and molecular results.

RESULTS: Excluding neurofibromatosis type 1, Ehlers-Danlos syndrome and RASopathies are discussed elsewhere. Diagnoses in this work comprised ectodermal dysplasias (n = 6), ichthyosis (n = 4), albinism (n = 4), tuberous sclerosis complex (n = 4), and incontinentia pigmenti (n = 3), in addition to 11 others with individual rare conditions. The sex ratio was 17:16 (M:F), consanguinity was present in 6/33 (18%), and the age at the first evaluation ranged from neonatal to 26 years (median 13.65 years). Negative results were 3/33 (9%), novel variants were 17/41 (41.4%), and 7/30 (23%) presented initially with a double molecular diagnosis, three confirming composed phenotypes.

CONCLUSIONS: Besides reporting 17 novel variants in 14 genes (BLM, CACNA1B, EDA, ELN, ENG, ERC6, EVC2, PNPLA1, PITCH1, PORCN, SIN3A, TP63, TYR, and WNT10B), the study also identified three atypical clinical presentations due to dual diagnoses, and the c.454C>T variant in the SDR9C7 gene, previously reported only in dogs, was, for the first time, confirmed as causative for ichthyosis in humans.

PMID:40428344 | DOI:10.3390/genes16050522

Genes (Basel). 2025 Apr 25;16(5):490. doi: 10.3390/genes16050490.

ABSTRACT

Background: Dyggve-Melchior-Clausen syndrome (DMC) is a rare autosomal recessive skeletal dysplasia characterized by dwarfism, coarse facial features, and intellectual disability. Caused by loss-of-function variants in the DYM gene, which encodes dymeclin, DMC is predominantly reported in consanguineous populations but remains poorly studied in South America. Methods: We report a 21-year-old Ecuadorian male with clinical features suggestive of DMC. Comprehensive clinical, radiological, and genetic evaluations were conducted, including clinical exome sequencing and Sanger sequencing, followed by an in silico analysis to assess the structural and functional consequences of the identified variant. Results: Exome sequencing identified a homozygous c.1878delA (p.Lys626fs) frameshift variant in the DYM gene, which was confirmed by Sanger sequencing as inherited from heterozygous parents. Variants of uncertain significance were detected in other skeletal dysplasia-related genes but did not correlate with the phenotype. A comprehensive review of reported DYM variants was also conducted. Conclusions: This report documents the first case of DMC in Ecuador and the second in South America, expanding the global understanding of DMC's genetic diversity. It underscores the value of next-generation sequencing in rare disease diagnostics and highlights the critical need for inclusive genomic research in underrepresented populations to improve the understanding of genetic heterogeneity and rare disease epidemiology.

PMID:40428312 | DOI:10.3390/genes16050490

Orphanet J Rare Dis. 2025 May 27;20(1):256. doi: 10.1186/s13023-025-03740-1.

ABSTRACT

Mechanistic target of rapamycin (mTOR) is a highly conserved serine/threonine kinase that regulates key cellular processes including cell growth, autophagy and metabolism. Hyperactivation of the mTOR pathway causes a group of rare and ultrarare genetic diseases. mTOR pathway diseases have diverse clinical manifestations that are managed by distinct medical disciplines but share a common underlying molecular basis. There is a now a deep understanding of the molecular underpinning that regulates the mTOR pathway but effective treatments for most mTOR pathway diseases are lacking. Translating scientific knowledge into clinical applications to benefit the unmet clinical needs of patients is a major challenge common to many rare diseases. In this article we expound how mTOR pathway diseases provide an opportunity to coordinate basic and translational disease research across the group, together with industry, medical research foundations, charities and patient groups, by pooling expertise and driving progress to benefit patients. We outline the germline and somatic mutations in the mTOR pathway that cause rare diseases and summarise the prevalence, genetic basis, clinical manifestations, pathophysiology and current treatments for each disease in this group. We describe the challenges and opportunities for progress in elucidating the underlying mechanisms, improving diagnosis and prognosis, as well as the development and approval of new therapies for mTOR pathway diseases. We illustrate the crucial role of patient public involvement and engagement in rare disease and mTOR pathway disease research. Finally, we explain how the mTOR Pathway Diseases node, part of the Research Disease Research UK Platform, will address these challenges to improve the understanding, diagnosis and treatment of mTOR pathway diseases.

PMID:40426219 | DOI:10.1186/s13023-025-03740-1

Infection. 2025 May 27. doi: 10.1007/s15010-025-02559-z. Online ahead of print.

ABSTRACT

Hemophagocytic lymphohistiocytosis (HLH) is an orphan disease characterized by excessive inflammation and poor outcome. We sought to further characterize clinical features, courses, and risk factors of secondary HLH (sHLH) triggered by infection (iHLH). 28 (43.1%) of 65 adult sHLH cases treated at our hospital from 2012-2024 were infection-associated. iHLH patients were mostly male (71.4%). Infectious agents most frequently detected were EBV (57.1%) and leishmania (14.3%). The median time to diagnosis was 13 [6.0;24.8] days. iHLH patients had a mortality rate of 39.3% (median follow-up time: 735 [336;1140] days), worse survival than patients with autoimmune-triggered (hazard ratio: 3.33 (1.01-11.10), p = 0.049), and better survival than patients with paraneoplastic HLH (hazard ratio: 0.19 (0.10-0.84), p = 0.002). Elevated levels of soluble interleukin-2 receptor (sIL2R; > 6,000 I/U), low thrombocyte counts (< 40 G/l), and a history of malignant disease were associated with adverse outcomes. Protracted time to diagnosis was associated with severe disease courses and with leishmaniosis. Further, sIL2R levels correlated positively with prolonged aPTT and thrombocytopenia, and hypertriglyceridemia with elevated INRs. Patients with an elevated sIL2R:ferritin ratio were more likely to have a history of malignant comorbidities. Taken together, sIL2R, thrombocytopenia, and a history of malignant disease are important prognostic factors of iHLH. Patients with high sIL2R levels or hypertriglyceridemia may be at higher risk of bleeding, and patients with elevated sIL2R:ferritin ratios should be assessed for possible malignant comorbidities. Lastly, increased awareness of the disease and newly emerging pathogens (i.e. leishmania) may shorten the time to diagnosis, and thus reduce severe courses of iHLH.

PMID:40425997 | DOI:10.1007/s15010-025-02559-z

Hum Mol Genet. 2025 May 27:ddaf082. doi: 10.1093/hmg/ddaf082. Online ahead of print.

ABSTRACT

Rare variants affecting the epigenetic regulator KDM2B cause a recently delineated neurodevelopmental disorder. Interestingly, we previously identified both a general KDM2B-associated episignature and a subsignature specific to variants in the DNA-binding CxxC domain. In light of the existence of a distinct subsignature, we set out to determine if KDM2B CxxC variants are associated with a unique phenotype and disease mechanism. We recruited individuals with heterozygous CxxC variants and assessed the variants' effect on protein expression and DNA-binding ability. We analyzed clinical data from 19 individuals, including ten previously undescribed individuals with seven novel CxxC variants. The core phenotype of the KDM2B-CxxC cohort is more extensive as compared to that of individuals with KDM2B haploinsufficiency. All individuals with CxxC variants presented with developmental delay, mainly in the speech and motor domain, in addition to variable intellectual disability and mild facial dysmorphism. Congenital heart defects were observed in up to 78% of individuals, with additional common findings including musculoskeletal, ophthalmological, and urogenital anomalies, as well as behavioral challenges and feeding difficulties. Functional assays revealed that while mutant KDM2B protein with CxxC variants can be expressed in vitro, its DNA-binding ability is significantly reduced compared to wildtype. This study shows that KDM2B CxxC variants cause a distinct neurodevelopmental syndrome, possibly through a molecular mechanism different from haploinsufficiency.

PMID:40420380 | DOI:10.1093/hmg/ddaf082

Lancet Rheumatol. 2025 Jul;7(7):e505-e518. doi: 10.1016/S2665-9913(25)00063-3. Epub 2025 May 23.

ABSTRACT

Existing guidelines for systemic lupus erythematosus (SLE) predominantly focus on common and major organ involvements. An international taskforce involving experts from three SLE expert groups (ie, the European Reference Network on Rare and Complex Connective Tissue and Musculoskeletal Diseases, the Systemic Lupus Erythematosus International Collaborating Clinics group, and the European Lupus Society) was established. A total of 119 participants contributed to the development of consensus therapeutic strategies for 24 rare SLE manifestations, using a multistep process. For SLE enteritis and pancreatitis, experts recommended hydroxychloroquine, glucocorticoids, and cyclophosphamide or mycophenolate mofetil. Rare lung conditions such as pneumonitis were also managed with cyclophosphamide if severe or with mycophenolate mofetil if not severe. SLE for myocarditis with hydroxychloroquine, glucocorticoids, and cyclophosphamide or mycophenolate mofetil, are recommended based on severity. For CNS manifestations, hydroxychloroquine, glucocorticoids, and cyclophosphamide or mycophenolate mofetil were common choices for treatment. For rare skin manifestations, the preferred strategy was a combination of hydroxychloroquine and glucocorticoids with anifrolumab or mycophenolate mofetil. This expert-based consensus provides a valuable framework for guiding therapeutic decisions where the available recommendations might be insufficient or inapplicable.

PMID:40418946 | DOI:10.1016/S2665-9913(25)00063-3

Genome Med. 2025 May 26;17(1):61. doi: 10.1186/s13073-025-01491-z.

ABSTRACT

Many people with rare diseases cannot access personalized therapies because they do not have a confirmed genetic diagnosis. Promising technologies including proteomics are underutilized in routine diagnostic practice. It is time to incorporate proteomics into the diagnostic workflow to shorten time to diagnosis and expand treatment options for rare disease.

PMID:40420250 | DOI:10.1186/s13073-025-01491-z

J Transl Med. 2025 May 26;23(1):586. doi: 10.1186/s12967-025-06609-w.

ABSTRACT

BACKGROUND: Approximately 60% of rare disease cases remain unsolved after exome and genome sequencing (ES/GS). Blood RNA sequencing (RNA-seq) complements DNA-level diagnosis by revealing the functional impact of variants on gene expression and splicing, but to what extent RNA-driven approaches offer diagnostic benefits across different scenarios-with and without pre-existing candidate variants-remains uncertain.

METHODS: 128 unrelated probands with suspected Mendelian disorders who had previously undergone ES/GS were recruited. A validation cohort (n = 7, with variants expected to alter RNA) and a test cohort (n = 121, including 10 with variants of uncertain significance (VUS) and 111 with no previously identified candidate variants) were analyzed. Blood RNA-seq was performed, and aberrant splicing (AS) and aberrant expression (AE) were detected using the DROP pipeline. SpliceAI predictions were compared with RNA-seq results for splicing-related VUS variants, and pathogenicity was re-evaluated. AS/AE outliers were evaluated for diagnostic potential in cases without candidate variants. The feasibility of an RNA-driven approach was assessed by ranking causal variant-associated aberrant events.

RESULTS: The pipeline correctly identified all expected AS/AE events in the validation cohort. In the test cohort with candidate VUS, RNA-seq provided a 60% (6/10) diagnostic uplift. Notably, SpliceAI predictions matched RNA-seq observations perfectly only in 40% of these VUS. A 2.7% (3/111) diagnostic uplift was achieved in the test cohort with no prior candidates. Overall, target AS and AE events ranked among the top eight in 14 of the 16 diagnosed cases using a purely RNA-driven approach; however, two cases would have been missed without prior candidate identification from DNA sequencing.

CONCLUSION: Blood RNA-seq is highly effective in refining the interpretation of splicing VUS, frequently leading to reclassification and diagnosis. Meanwhile, RNA-driven identification of causal variants shows a more modest yield in cases without prior candidates. This study supports an RNA-complementary approach as the preferred strategy for clinical utility.

PMID:40420094 | DOI:10.1186/s12967-025-06609-w

JMIR Infodemiology. 2025 May 26;5:e69040. doi: 10.2196/69040.

ABSTRACT

BACKGROUND: Eosinophilia and hypereosinophilic syndrome (HES) are rare disorders grouped under the term hypereosinophilic disorders. They are diagnosed based on an increased number of eosinophils. They can also cause serious symptoms, including skin, lung, and gastrointestinal problems. These disorders are very rarely recognized due to their rarity and misdiagnosis.

OBJECTIVE: This study analyzes public interest in hypereosinophilic disorders using data on internet search volume in Germany between 2020 and 2023. Objectives include identifying frequently searched terms, evaluating temporal trends, analyzing seasonal patterns, evaluating geographic differences in search behavior, and identifying unmet information needs and frequently searched risk factors.

METHODS: A retrospective analysis using Google Ads Keyword Planner gathered monthly search volume data for 12 German terms related to hypereosinophilic disorders. These terms were selected based on their medical relevance and common usage identified from medical literature. Data were analyzed descriptively, with trends, seasonal variations, and geographical distributions examined. Chi-square tests and correlation analysis assessed statistical significance.

RESULTS: A total of 178 keywords were identified, resulting in a search volume of 1,745,540 queries. The top keyword was "eosophile," a misspelling, followed by "eosinophilia" and "HES." The main categories included "Eosinophilia," "Eosinophils," and "Churg-Strauss syndrome." Temporal analysis showed seasonal growth in search volumes, peaking in January 2023, with higher interest during winter. Geographical analysis showed regional variations.

CONCLUSIONS: This research shows a growing public interest in eosinophilic diseases, reflected by a steadily increasing search volume over time. This is particularly evident in searches for basic definitions and diagnostic criteria, such as "eosinophils" or "symptoms of eosinophilic diseases." This increase in search volume, which peaked in January 2023, indicates an increased interest in accurate and readily available information for rare conditions.

PMID:40418815 | DOI:10.2196/69040

AMIA Annu Symp Proc. 2025 May 22;2024:1275-1283. eCollection 2024.

ABSTRACT

Large language models (LLMs) have shown great promise in clinical medicine, but their adoption in real-world settings has been limited by their tendency to generate incorrect and sometimes even toxic statements. This study presents a reliable rare disease intelligent agent called RDguru, which incorporates authoritative and reliable knowledge sources and tools into the reasoning and response of LLMs. In addition to answering questions about rare diseases more accurately, RDguru can conduct medical consultations to provide differential diagnosis decision support for clinical users. The DQN-based multi-source fusion diagnostic model integrates three diagnostic recommendation strategies, GPT-4, PheLR, and phenotype matching. Testing on 238 real rare disease cases showed that RDguru's top 10 list of recommended diagnoses was able to recall 69.1% of real diagnoses, the top 5 recommended diagnoses were able to recall 63.6% of real diagnoses, and the top ranked diagnosis was able to achieve an accuracy rate of 41.9%.

PMID:40417483 | PMC:PMC12099370

Drug Des Devel Ther. 2025 May 20;19:4201-4220. doi: 10.2147/DDDT.S506112. eCollection 2025.

ABSTRACT

OBJECTIVE: This study analyzes the current research landscape and trends in orphan drug development, providing insights for future advancements in the field.

METHODS: Gathering pertinent material from the China National Knowledge Infrastructure (CNKI) and Web of Science databases. Microsoft Office Excel 2017, VOSview 1.6.20, and CiteSpace 6.3R2 were utilised to summarise the present research state and offer insights into research hotspots in the domain of orphan drugs.

RESULTS: A total of 3598 research papers were included, with Chinese research showing a continuous upward trend, while international research has entered a slow development stage. The field of orphan drug research has formed a sizable research team, and cooperation between international institutions is relatively mature. Meanwhile, the United States and the United Kingdom have strong influence in this research field, while China lacks international cooperation. The research focus in this field mainly involves the development and clinical application of orphan drugs, and domestic and foreign research also has its own emphasis. Maintain consistency in clinical trials and medication support for orphan drugs both domestically and internationally; And foreign research has obvious advantages in the development of orphan drugs. Keyword emergence research indicates that the clinical accessibility and regulatory approval of orphan drugs have become a prominent issue of interest both nationally and globally.

CONCLUSION: This study systematically summarises and examines the current research status and emerging trends in the global orphan drug sector by analysing relevant literature from 2000 to 2024 through bibliometric methods. It further delineates the similarities and differences in orphan drug research domestically and internationally, offering valuable references for future investigations in this domain.

PMID:40416799 | PMC:PMC12103199 | DOI:10.2147/DDDT.S506112

Genome Med. 2025 May 22;17(1):58. doi: 10.1186/s13073-025-01467-z.

ABSTRACT

BACKGROUND: Only half of individuals with suspected rare diseases receive a genetic diagnosis following genomic testing. A genetic diagnosis allows access to appropriate care, restores reproductive confidence and reduces the number of potentially unnecessary interventions. A major barrier is the lack of disease agnostic functional tests suitable for implementation in routine diagnostics that can provide evidence supporting pathogenicity of novel variants, especially those refractory to RNA sequencing.

METHODS: Focusing on mitochondrial disease, we describe an untargeted mass-spectrometry based proteomics pipeline that can quantify proteins encoded by > 50% of Mendelian disease genes and > 80% of known mitochondrial disease genes in clinically relevant sample types, including peripheral blood mononuclear cells (PBMCs). In total we profiled > 90 individuals including undiagnosed individuals suspected of mitochondrial disease and a supporting cohort of disease controls harbouring pathogenic variants in nuclear and mitochondrial genes. Proteomics data were benchmarked against pathology accredited respiratory chain enzymology to assess the performance of proteomics as a functional test. Proteomics testing was subsequently applied to individuals with suspected mitochondrial disease, including a critically ill infant with a view toward rapid interpretation of variants identified in ultra-rapid genome sequencing.

RESULTS: Proteomics testing provided evidence to support variant pathogenicity in 83% of individuals in a cohort with confirmed mitochondrial disease, outperforming clinical respiratory chain enzymology. Freely available bioinformatic tools and criteria developed for this study ( https://rdms.app/ ) allow mitochondrial dysfunction to be identified in proteomics data with high confidence. Application of proteomics to undiagnosed individuals led to 6 additional diagnoses, including a mitochondrial phenocopy disorder, highlighting the disease agnostic nature of proteomics. Use of PBMCs as a sample type allowed rapid return of proteomics data supporting pathogenicity of novel variants identified through ultra-rapid genome sequencing in as little as 54 h.

CONCLUSIONS: This study provides a framework to support the integration of a single untargeted proteomics test into routine diagnostic practice for the diagnosis of mitochondrial and potentially other rare genetic disorders in clinically actionable timelines, offering a paradigm shift for the functional validation of genetic variants.

PMID:40400026 | DOI:10.1186/s13073-025-01467-z

Curr Rheumatol Rep. 2025 May 21;27(1):24. doi: 10.1007/s11926-025-01189-6.

ABSTRACT

PURPOSE OF THIS REVIEW: Rare diseases, although individually infrequent, collectively impact a substantial number of people. Collaborative translational research using biospecimens is essential for advancing our understanding of the diverse characteristics and pathophysiology of rare diseases. Biobanks play a pivotal role in this endeavor by collecting, processing, transporting, and storing biospecimens, thereby serving as invaluable resources for medical research. In this review, we explore currently available biobanks, with a specific focus on those dedicated to rare rheumatic diseases. We also examine accessible best practice guidelines for establishing and maintaining high-quality biobanks, discuss the limitations and propose future directions for enhancing biobanking efforts in rare disease research.

RECENT FINDINGS: Advances in molecular and genomic technologies have expanded the role of biobanks, enhancing biomarker discovery and precision medicine. However, despite growth in biobanking capabilities, key challenges persist concerning ethics, interoperability, and biospecimen exchange, prompting active responses by various regulatory and governing bodies. Biobanking has transformed rare disease research. Strengthening national and international collaborations is essential for driving progress in this field and accelerating the development of novel therapeutic and precision medicine approaches.

PMID:40397074 | DOI:10.1007/s11926-025-01189-6

Dtsch Med Wochenschr. 2025 Jun;150(12):703-712. doi: 10.1055/a-2145-7495. Epub 2025 May 19.

ABSTRACT

Bronchiectasis is a worldwide inflammatory disease with different epidemiology and heterogenous etiology. The disease burden is high for patients and economic costs can be immense. So far there are no special disease modifying drugs available for patients with bronchiectasis other than cystic fibrosis. With rising numbers of newly diagnosed patients (prevalence 120/100000 in Germany) due to different reasons (idiopathic, postinfectious, genetic, asthma, COPD etc.) the awareness for this once called orphan disease should rise - not only among pulmonologists but also among general care practitioners. This article focuses on diagnostic algorithms and multimodal treatment options based on the latest studies and the recently published German bronchiectasis guideline from May 2024. It outlines what general care practitioners can do for their patients, what they should consider when treating an exacerbation and that special surveillance of these patients is needed in centers with expertise in this disease due to its complexity. With upcoming treatment options just as disease modifying drugs like DDP-1 inhibitors or inhaled antibiotics one can expect a change in disease treatment and outcome. Therefore, it is more and more important to raise awareness for bronchiectasis starting at the very basis when patients present at their general care practitioner with recurring productive cough, exacerbations, and further cardinal symptoms of bronchiectasis disease.

PMID:40388981 | DOI:10.1055/a-2145-7495

Am J Manag Care. 2025 May;31(5):240-244. doi: 10.37765/ajmc.2025.89673.

ABSTRACT

OBJECTIVES: To quantify the magnitude of altruism value as applied to a hypothetical new treatment for a rare, severe pediatric disease: Duchenne muscular dystrophy (DMD).

STUDY DESIGN: Prospective survey of individuals not planning to have children in the future.

METHODS: A survey was administered to US adults (aged ≥ 21 years) not intending to have a child in the future to elicit willingness to pay (WTP) for government insurance coverage for a new hypothetical DMD treatment that improves mortality and morbidity relative to the current standard of care. A multiple random staircase design was used to identify an indifference point between status quo government insurance coverage and coverage with additional cost in taxes that would cover the treatment if unrelated individuals had a child with DMD. Altruism value was calculated as respondents' mean WTP.

RESULTS: Among 215 respondents, 54.9% (n = 118) were aged 25 to 44 years and 80.0% (n = 172) were women. Mean WTP for insurance coverage of the hypothetical DMD treatment for others was $80.01 (95% CI, $41.64-$118.37) annually, or $6.67 monthly, after adjustment to account for disease probability overestimation. The adjusted altruism value was higher than the ex ante per-person value using traditional cost-effectiveness approaches ($45.30/year). Without adjusting, individuals were willing to pay $799.11 annually ($66.59 monthly).

CONCLUSIONS: Despite no possibility of accruing health benefits directly for themselves or their children, individuals had a high WTP for government insurance coverage of a novel treatment for this rare, severe pediatric disease.

PMID:40387711 | DOI:10.37765/ajmc.2025.89673

Biotechnol Lett. 2025 May 17;47(3):56. doi: 10.1007/s10529-025-03596-2.

ABSTRACT

Orphan diseases comprise a range of disorders that individually affect a small percentage of people, but collectively impact millions of people worldwide. Patients with this disorder often face significant challenges in diagnosis, treatment, and access to care due to their rare nature and limited understanding and treatment options. In recent years, significant advancements have been made in the global healthcare in addressing the accessibility of essential treatments and medicines, but still challenges persist particularly related to orphan drugs (to treat rare diseases) in the developing world. The accessibility of orphan drugs remains a major challenge, where patients face barriers such as high costs, limited availability, and inadequate healthcare infrastructure. The high cost associated with orphan drugs presents a barrier to affordability for both patients and healthcare systems, causing disparities in access to life-saving treatments. The molecular farming approach utilizing plant-based production systems for recombinant protein production offers a hope for overcoming barriers to orphan drug access in resource-constrained settings. Molecular farming has the potential to produce a wide range of therapeutic proteins and biologics for the treatment of various rare diseases. The FDA approval of plant-derived proteins for the treatment of Gaucher disease (Elelyso) and Fabry disease (Elfabrio) highlights the potential of plant-based expression systems for the development of suitable drugs targeting niche and orphan diseases. This review examines the potential of the plant system in producing orphan drugs and also highlights the opportunities and challenges related to orphan drug manufacturing.

PMID:40381123 | DOI:10.1007/s10529-025-03596-2

Stud Health Technol Inform. 2025 May 15;327:1270-1274. doi: 10.3233/SHTI250602.

ABSTRACT

Electronic Health Records (EHRs) provide valuable longitudinal data for tracking disease progression, especially in rare diseases like ciliopathies which often involve chronic renal decline. While important biomarkers are available in structured databases, crucial information such as external lab tests and detailed disease history may only be found in clinical narratives. This study aims to enrich structured datasets with unstructured clinical text and assess its impact on estimating chronic kidney disease progression in ciliopathy patients. Our results demonstrate that data enrichment increased the number of eligible patients for longitudinal analysis by 73.5%, expanded available measurements by 189%, and significantly extended the median follow-up duration from 3.2 to 6.6 years. Using linear mixed regression to model individual estimated glomerular filtration (eGFR) rate trajectories over age, we found that data enrichment reduced standard errors by 30%, indicating a substantial increase in precision and reliability. These findings underscore the value of EHR data enrichment for longitudinal analysis in rare disease research.

PMID:40380706 | DOI:10.3233/SHTI250602

Stud Health Technol Inform. 2025 May 15;327:123-127. doi: 10.3233/SHTI250286.

ABSTRACT

Rare diseases, while individually rare, cumulatively affect a large population, and patients often undergo long and arduous diagnostic odysseys. Toward the goal of supporting earlier diagnosis of rare diseases, we developed generalizable methods of extracting rare diseases and phenotypes from structured electronic health records and clinical notes. We analyzed the distributions of the age of onset of phenotypes per disease to identify disease-phenotype associations, producing a dataset with over 500 thousand associations covering 2300 rare diseases. Disease-phenotype associations are characterized by disease prevalence and mean age of onset of the phenotype to aid phenotype selection according to the priorities of the clinical decision support task.

PMID:40380398 | DOI:10.3233/SHTI250286

Stud Health Technol Inform. 2025 May 15;327:32-36. doi: 10.3233/SHTI250268.

ABSTRACT

Rare diseases are challenging to diagnose and collectively affect a large fraction of the population. This work sought to develop an approach to generate models for probabilistic reasoning focused on the presence of a specified phenotypic abnormality. The approach generates a Bayesian network, a graphical AI model that uses probability to reason under uncertainty, that includes all diseases that can cause the specified abnormality as well as all phenotypic abnormalities caused by those diseases. The approach efficiently computes the probabilities of the possible diagnoses and evaluates the impact of additional evidence. One can use the model to identify the observations that yield the greatest information to reduce uncertainty. An example model for diagnosis of a finding of enlarged kidney is presented to demonstrate the feasibility and advantages of the approach. Further work includes incorporation of age of onset and inheritance pattern of the diseases, hierarchical relationships among diseases and phenotypic abnormalities to allow diagnosis based on information at varying levels of granularity, and user interfaces to simplify interaction with the models.

PMID:40380380 | DOI:10.3233/SHTI250268