Journal of Inherited Metabolic Disease最新文献

{"title":"Long-Term Outcomes of Chenodeoxycholic Acid Therapy for Cerebrotendinous Xanthomatosis: A Nationwide Study on Prognostic Factors and Treatment Response","authors":"Tanyel Zubarioglu,&nbsp;Banu Kadıoğlu-Yılmaz,&nbsp;Engin Köse,&nbsp;Pelin Teke-Kısa,&nbsp;Mehmet Cihan Balcı,&nbsp;Havva Yazıcı,&nbsp;Burcu Özturk-Hişmi,&nbsp;Abdurrahman Akgün,&nbsp;Deniz Kor,&nbsp;Sevil Yıldız,&nbsp;Gonca Kılıç-Yıldırım,&nbsp;Erdoğan Soyuçen,&nbsp;Aylin Akçalı,&nbsp;Yılmaz Yıldız,&nbsp;Aslı Durmuş,&nbsp;Dilek Güneş,&nbsp;Pembe Soylu-Üstkoyuncu,&nbsp;Çiğdem Seher Kasapkara,&nbsp;Şahin Erdöl,&nbsp;Emine Göksoy,&nbsp;Halil Tuna Akar,&nbsp;Haluk Gümüş,&nbsp;Ahmet Hakan Ekmekçi,&nbsp;Fatma Tuba Eminoğlu,&nbsp;Nur Arslan,&nbsp;Haşmet Ayhan Hanağası,&nbsp;Ebru Canda,&nbsp;Emine Genç,&nbsp;Işıl Özer,&nbsp;Ayşegül Gündüz,&nbsp;Ertuğrul Kıykım,&nbsp;Çiğdem Aktuğlu-Zeybek","doi":"10.1002/jimd.70069","DOIUrl":"https://doi.org/10.1002/jimd.70069","url":null,"abstract":"<div>\u0000 \u0000 <p>Cerebrotendinous xanthomatosis (CTX) is a treatable neurometabolic disorder. Chenodeoxycholic acid (CDCA) is the first-line treatment and can potentially halt disease progression if initiated before neurologic symptoms appear. This nationwide, multicenter study evaluates the long-term effects of treatment in 86 genetically confirmed patients with CTX receiving CDCA for ≥ 6 months, focusing on neurologic and extraneurologic outcomes, prognostic factors, and biochemical response. Clinical and biochemical parameters were recorded at baseline and follow-up, and neurological outcomes were assessed using neurological disability scores. Our results indicate a critical age of 28 years for the start of treatment. Patients diagnosed before 28 years showed 100% neurological stabilization or improvement, whereas patients diagnosed later had a higher rate of disease progression (<i>p</i> &lt; 0.05). CDCA effectively stabilized or improved pyramidal and cerebellar symptoms, although myoclonus and parkinsonism remained less responsive. Psychiatric symptoms showed a lower treatment response, with psychosis being the most refractory finding. CDCA resulted in a strong and sustained reduction in cholestanol levels, although biochemical response did not always correlate with clinical improvement. Longer diagnostic delay and presence of anxiety and pyramidal/cerebellar symptoms were associated with poorer outcomes. Notably, a cholestatic child, for whom liver transplantation had initially been considered, recovered completely under CDCA therapy. Our results show that early diagnosis and initiation of CDCA therapy significantly improve neurological outcomes in CTX. However, even in late-diagnosed patients, treatment continues to be beneficial, demonstrating that it is never too late to start therapy. Biochemical response does not always predict clinical improvement; multidisciplinary follow-up is essential.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial Comment to Regulatory News","authors":"Carla E. M. Hollak,&nbsp;Natalja Bouwhuis","doi":"10.1002/jimd.70071","DOIUrl":"https://doi.org/10.1002/jimd.70071","url":null,"abstract":"&lt;p&gt;Access to affordable chenodeoxycholic acid (CDCA) is essential for patients with cerebrotendinous xanthomatosis (CTX), a rare, inherited metabolic disorder that is likely to require lifelong treatment. CDCA was discovered in the 1970s as a treatment to prevent neurological decline and improve the quality of life of CTX patients. It is therefore essential that it is available at a reasonable price.&lt;/p&gt;&lt;p&gt;In 2021, the Dutch Authority for Consumers and Markets (ACM) fined Leadiant Biosciences nearly €20 million for abusing its dominant market position. After acquiring the rights to CDCA in 2008, Leadiant increased the price from €46 to over €14 000 per 100 capsules by 2017—despite the drug having been available and used off label for decades. The ACM concluded that these price hikes were not justified by innovation or new research and amounted to unfair exploitation of market exclusivity. Leadiant appealed the ruling, but in February 2025, the District Court concluded that ACM's decision was right [&lt;span&gt;1&lt;/span&gt;]. Additional fines by other EU member states were imposed on Leadiant. Because the pricing jeopardized access in the Netherlands, a magistral (compound) preparation of CDCA was used by patients instead.&lt;/p&gt;&lt;p&gt;Following the registration of CDCA for treatment of CTX in the EU, it is important that CDCA (chenodiol, brand name Ctexli) is now also approved in the United States, marketed by Mirum Pharmaceuticals [&lt;span&gt;2&lt;/span&gt;]. This offers hope for wider access to this crucial treatment. Of interest is that CDCA was historically used to treat gallstones but has already been used for decades to treat CTX, with many reports showing its well-established use. In the EU, retrospective data were sufficient to approve the product. However, in the US, a double-blind study was requested in a small group of patients, which showed that the treatment, not surprisingly, was effective in reducing the characteristic bile acid accumulations in plasma and urine [&lt;span&gt;2&lt;/span&gt;]. Long-term clinical outcomes were considered unachievable, as the treatment is, indeed, standard of care. While it is important to support approval with high-quality data, it is interesting to investigate whether the investment in this small-scale study will support the argument for the price of the drug in the US. A recent publication mentions a list price of US$60487 per 100 tablets [&lt;span&gt;3&lt;/span&gt;]. This equates to an annual cost for an adult patient of over US$660000. That's even four times higher than in the EU. For the marketing of this type of drug, whose value has in fact long been established, a cost-based price would be more socially justifiable. As healthcare professionals and patients, we want to emphasize that regulatory approval must be followed by ethical pricing to ensure that all patients—regardless of geographic location or socioeconomic status—receive the medicines they need.&lt;/p&gt;&lt;p&gt;This case underscores the crucial role of oversight and advocacy in protecting patien","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144688013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Brief History of Inherited Metabolic Diseases: A Personal 60 Years Clinical Flashback","authors":"Jean-Marie Saudubray,&nbsp;Manuel Schiff","doi":"10.1002/jimd.70063","DOIUrl":"https://doi.org/10.1002/jimd.70063","url":null,"abstract":"<p>The concept of IMDs has evolved over a century from rare deficits in amino acid catabolism diagnosed by the accumulation of biochemical markers such as phenylketonuria (PKU) to diseases affecting organelle metabolism, synthesis of complex molecules, and cellular trafficking. Small-molecule accumulation disorders form the major group of treatable IMDs. Do not miss these metabolic emergencies! IMDs currently number over 1800 and include all medical specialties. The specificity of true “molecular internists,” metabolic specialists, lies in the in-depth knowledge of metabolic pathways and the understanding of the pathophysiology of the deficits underlying the treatments (“precision medicine”). Neurology is massively impacted, but cerebral metabolism remains largely misunderstood. Genetic analyses are becoming increasingly important for diagnosis but must be complemented by biochemical investigations, which sometimes have greater diagnostic specificity and provide functional information at the phenotype level. Biochemical analyses remain essential for monitoring treatment or even for diagnosis. Finally, contrary to early expectations, newborn screening such as that for phenylketonuria, leading to preventive therapy, could be extended to a significant though limited number of IMDs. Currently, there are numerous initiatives that include genetic screening combined with biochemical testing or that extend screening to lysosomal diseases potentially treatable by enzyme or gene therapy.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144681424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to “Outcome of Haemopoietic Stem Cell Transplantation in 21 Patients With Alpha-Mannosidosis”","authors":"","doi":"10.1002/jimd.70068","DOIUrl":"https://doi.org/10.1002/jimd.70068","url":null,"abstract":"<p>R. Šáhó, R. Formánková, J. B. Eisengart, et al., “Outcome of Haemopoietic Stem Cell Transplantation in 21 Patients With Alpha-Mannosidosis,” <i>Journal of Inherited Metabolic Disease</i> 48, no. 4 (2025): e70047, https://doi.org/10.1002/jimd.70047.</p><p>The authors have added Dr. Chiara Monachesi as a co-author to the paper.</p><p>Chiara Monachesi</p><p>Division of Pediatrics, Department of Clinical Sciences, Azienda Ospedaliero Universitaria delle Marche, Presidio Salesi, Ancona, Italy</p><p>Dr. Monachesi has no conflict of interest.</p><p>Dr. Monachesi's contribution: As the majority of co-authors, she was the treating physician and transplant physician performing the HSCT, examinations, and follow-up in the patients.</p><p>There are no other changes in the author list or affiliations.</p><p>We apologize for this error.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70068","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144646844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced Pluripotent Stem Cells for the Treatment of Lysosomal Storage Disorders","authors":"Maryann Lorino,&nbsp;Bei Qiu,&nbsp;Brian Bigger","doi":"10.1002/jimd.70064","DOIUrl":"https://doi.org/10.1002/jimd.70064","url":null,"abstract":"<p>Lysosomal disorders (LSDs) are a group of rare metabolic disorders, with an overall incidence of 1:4800 to 1:8000 live births. LSDs are primarily caused by dysfunctional lysosomal enzymes, which typically lead to the progressive accumulation of substrates within cellular lysosomes. As a result, patients experience a wide array of somatic symptoms such as visceromegaly, cardiopulmonary abnormalities, and respiratory and urinary infections. Additionally, over two-thirds of LSD subtypes have a neurological component, and without treatment, patients experience neurodegeneration, cognitive decline, and life expectancies spanning infancy to adulthood. At present, there is no therapy that rescues the degenerative neuropathology of LSDs, and current developments, such as brain-targeted enzyme replacement therapy, hematopoietic stem cell transplantation, and even gene therapy, can only prevent further neurodegeneration. However, recent advancements involving induced pluripotent stem cells (iPSCs) have demonstrated that stem cells may harbor the potential to both recapitulate the phenotype of neuropathic LSDs in vitro, as well as serve as a vector for regeneration in vivo, by replacing cells and neurons damaged by disease progression. This review reports the current state of iPSC technology in LSD research, and the pathway by which iPSCs are translated from disease modeling to serving as a regenerative therapeutic for neuropathic LSDs in the clinic.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70064","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness and Safety of Personalized Cholic Acid Treatment in Patients With Bile Acid Synthesis Defects","authors":"Yasmin Polak,&nbsp;Elles Marleen Kemper,&nbsp;Marc Engelen,&nbsp;Femke C. C. Klouwer,&nbsp;Kevin Berendse,&nbsp;Frédéric M. Vaz,&nbsp;Bart G. P. Koot,&nbsp;Eleonora (Noortje) L. Swart,&nbsp;Carla E. M. Hollak","doi":"10.1002/jimd.70062","DOIUrl":"https://doi.org/10.1002/jimd.70062","url":null,"abstract":"<p>Bile acid synthesis defects (BASDs) comprise a group of rare, often severe, metabolic disorders. Bile acid replacement therapy decreases toxic bile acid intermediates production and improves biochemical profiles, potentially delaying or stabilizing disease progression. An open label, non-randomized trial with cholic acid (CA) supplementation included six patients with α-methylacyl-CoA racemase (AMACR) deficiency and one patient with 3β-hydroxy-Δ⁵-C₂₇-steroid oxidoreductase deficiency. Patients received up to 20 mg/kg/day CA for 3.5 years, adjusted for biochemical response, side effects, and clinical evaluation. Bile acid metabolites, liver enzymes, liver stiffness, and neurological symptoms were evaluated at baseline and during follow-up. CA was well tolerated in children (<i>n</i> = 3), allowing for higher doses. Adults (<i>n</i> = 4) experienced more side effects, primarily diarrhea and other gastrointestinal symptoms. Children's transaminase levels normalized during treatment, while adults' levels remained normal throughout. Elevated C₂₇-bile acid intermediates, C₂₉-dicarboxylic acid, and pristanic acid were observed in all AMACR patients. C₂₇-bile acids and C₂₉-dicarboxylic acid decreased with treatment, while pristanic acid fluctuated and remained elevated. No clinically relevant changes were observed in liver elasticity, fat-soluble vitamin levels, neurological assessment, or growth (in children). One adult developed hepatocellular carcinoma during treatment. CA treatment is generally safe, with acceptable tolerance and a marked biochemical response observed in children, although biomarker levels remained markedly elevated. In adults, however, the balance shifts negatively, with side effects outweighing the (biochemical) benefits. A longer study is necessary to evaluate the impact of CA treatment on the clinical relevance of the observed biochemical response.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70062","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144598276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramolecular Epistatic Interactions in Genetic Diseases","authors":"Tomás Oliveira-Madureira,&nbsp;Mariana Santos-Pereira,&nbsp;Luísa Azevedo","doi":"10.1002/jimd.70059","DOIUrl":"https://doi.org/10.1002/jimd.70059","url":null,"abstract":"<div>\u0000 \u0000 <p>A key factor influencing the structural and functional impact of amino acid substitutions in disease-associated genes involves the background genetic variation. Epistatic interactions between co-evolving positions in the same gene result in the interdependence of each site with its interacting partners. Evidence supporting the role of these interactions is exemplified in the occurrence of human disease-associated alleles in the genome of non-human species. Although several explanations can contribute to this phenomenon, one possibility is the occurrence of compensatory interacting sites that can fully, or partially, restore the pathogenic effect, contributing to the maintenance of protein structure and proper function. These interactions create genetic contexts that are revisited here through the analysis of literature data for specific proteins, with a particular focus on proteins involved in inborn errors of metabolism.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589591","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Metabolomics, Lipidomics, and Acylcarnitines Are Associated With Vision and Genotype but Not With Dietary Intake in Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHADD)","authors":"Hak Chung,&nbsp;Dongseok Choi,&nbsp;Ashley Gregor,&nbsp;Elaine Sim,&nbsp;Alison Lau,&nbsp;Danielle Black,&nbsp;Hannah L. Scanga,&nbsp;Angela Linshinski,&nbsp;Mark E. Pennesi,&nbsp;Jose-Alain Sahel,&nbsp;Ken K. Nischal,&nbsp;Paul Yang,&nbsp;Lesley Everett,&nbsp;Jerry Vockley,&nbsp;Dietrich Matern,&nbsp;Cary O. Harding,&nbsp;Melanie B. Gillingham","doi":"10.1002/jimd.70060","DOIUrl":"https://doi.org/10.1002/jimd.70060","url":null,"abstract":"<div>\u0000 \u0000 <p>3-hydroxy acylcarnitines (3-OH-ACs) are key biomarkers for screening of long-chain 3-hydroxyacyl-CoA dehydrogenase and trifunctional protein deficiencies (LCHADD/TFPD). The utility of this biomarker for disease monitoring in identified patients remains debated, and recent suggestions have highlighted the potential use of lipidomics for diagnosis, monitoring, prognosis, and/or identification of new biomarkers. We evaluated the use of omics in LCHADD/TFPD patients by analyzing plasma acylcarnitine profiles, metabolomics, and lipidomics, combined with genotype, visual assessments, and dietary records. Fasting plasma from 39 participants with LCHADD/TFPD and 32 control subjects were analyzed through untargeted metabolomic and lipidomic analyses. In LCHADD/TFPD participants, acylcarnitine profiling, visual and retinal function assessments were performed, and 3-day diet records were collected. Relationships between acylcarnitines, metabolomics, lipidomics, along with visual outcomes and dietary intake were investigated. Plasma of LCHADD/TFPD participants exhibited elevated 3-OH-ACs, which correlated with genotype and visual outcomes. Metabolomics successfully distinguished LCHADD/TFPD from controls, and the biggest divergence was observed in lipid pathways. Metabolomic profiles tightly correlated with 3-OH-ACs, genotype, and visual outcomes. Lower concentrations of total lipids and some individual lipid species such as phosphoethanolamines (PE) were detected in LCHADD/TFPD, except for elevations in several certain triglycerides. LCHADD/TFPD participants followed a diet low in long-chain fat (LCFA) as recommended. LCFA intake did not correlate with either plasma 3-OH-ACs or metabolomics. 3-OH-ACs are strong consistent biomarkers of LCHADD/TFPD that are associated with clinical parameters of vision and genotype. We did not observe a relationship between dietary LCFA intake and 3-OH-ACs.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene Dosage Sensitivity and Human Genetic Diseases","authors":"Reiner A. Veitia,&nbsp;Johannes Zschocke,&nbsp;James A. Birchler","doi":"10.1002/jimd.70058","DOIUrl":"https://doi.org/10.1002/jimd.70058","url":null,"abstract":"<p>Here we review the historical background and contemporary insights into genetic dominance, focusing on haploinsufficiency (HI), that is, when the function of only one allele of a gene is not enough to ensure a normal phenotype in a diploid organism. A related phenomenon is triplosensitivity, that is, pathogenic effects when there are three instead of two copies of some 'genes'. The importance of gene dosage issues was realized in humans when whole chromosomal abnormalities (aneuploidy) could be linked to clinical phenotypes such as Down, Edwards, and Patau syndromes. Subsequently, subtler chromosomal deletions and duplications have been shown to be responsible for many developmental syndromes. In several cases, a dosage-sensitive gene mapping to the relevant regions has been implicated as causal. We delve into the mechanisms of HI, especially due to direct protein insufficiency and subunit imbalances in the context of multi-subunit complexes. We show how the nonlinearity inherent to the relationship between genotype and phenotype is responsible for the dominance of the underlying genetic variants. We also explore why increased gene dosage can lead to abnormal phenotypes. Examples include trisomy or segmental genomic duplications in humans and oncogene amplification in cancers. Finally, we examine a few cases of genetic synergy, where the combined effect of two or more variants amplifies their individual effects, underlying a distinguishable phenotype. Further research is required to elucidate the dynamics of multicomponent interactions to unravel the mechanistic complexities of genetic dominance, inter-gene interactions, and their implications for disease.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144589569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression Profiles of Exosomal miRNAs in Gaucher Patients and Their Association With Severity of Bone Involvement","authors":"Irene Serrano-Gonzalo,&nbsp;Laura López de Frutos,&nbsp;Maria Sancho-Albero,&nbsp;Mercedes Roca-Espiau,&nbsp;Ralf Köhler,&nbsp;Pilar Giraldo","doi":"10.1002/jimd.70061","DOIUrl":"https://doi.org/10.1002/jimd.70061","url":null,"abstract":"<p>Bone manifestations are one of the most prevalent complications in patients with Gaucher disease (GD). Bone involvement is evaluated by using imaging methods, and there are different scores to assess its severity. However, there are no biomarkers that allow us to predict these manifestations. In recent years, several miRNAs have been associated with bone involvement and postulated as excellent bioavailable biomarkers. This study aims to identify a miRNA expression profile from plasma exosomes and to associate it with the severity of bone involvement in patients with GD. This study included 60 untreated patients with GD with bone involvement, who were classified according to the S-MRI score into three groups: mild disease (MiBD; S-MRI &lt; 5), moderate disease (MoBD; S-MRI: 5–11), or severe disease (SBD; S-MRI &gt; 11). Plasma exosomes were purified, and miRNAs were extracted and identified by next-generation sequencing (NGS) technology. Differentially expressed miRNAs were validated by droplet digital PCR (ddPCR). In the patients' groups classified by S-MRI, the median ages (Q1–Q3) were: MiBD 19.0 (4.00–40.00), MoBD 40.5 (28.25–56.00), and SBD 37.5 (31.25–47.00) years. When comparing groups, we found 12 differentially expressed exosomal miRNAs. After validation, four miRNAs were identified as differentially expressed: hsa-miR-127-3p, hsa-miR-184, hsa-miR-197-3p, and hsa-miR-660-5p. Notably, hsa-miR-127-3p, hsa-miR-660-5p, and hsa-miR-184 were correlated with the presence of infarcts, necrosis, and the degree of infiltration into the spine, pelvis, and femur. These three miRNAs could serve as bioavailable biomarkers to assess bone disease in GD, and further revalidation with a higher number of patients.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144573483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}