Journal of Inherited Metabolic Disease最新文献

{"title":"How Much AI Can Scientific Publishing Tolerate?","authors":"Verena Peters, Matthias Baumgartner, Nicola Brunetti-Pierri, Shamima Rahman, Johannes Zschocke, D Sean Froese","doi":"10.1002/jimd.70197","DOIUrl":"10.1002/jimd.70197","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":"e70197"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147874409","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":"Effectiveness of Riboflavin in Inherited Metabolic Diseases: A Systematic Review.","authors":"Bregje Jaeger, Nina N Stolwijk, Femke Aaldering, Charlotte A Ruys, Marije Smits, Nicole I Wolf, Carla E M Hollak, Annet M Bosch","doi":"10.1002/jimd.70190","DOIUrl":"10.1002/jimd.70190","url":null,"abstract":"<p><p>Riboflavin (RF, vitamin B2) is an essential vitamin of which the co-factors are critical to numerous cellular processes. RF is used as a treatment for inherited metabolic diseases (IMDs), although its effectiveness in many disorders has not been established. We aim to summarize all available data on the efficacy and safety of RF in the management of IMDs. A systematic literature search was conducted for articles reporting the effectiveness of RF in IMDs. RF therapy was considered \"effective\" in an IMD if more than 75% of patients showed a positive response, \"uncertain\" in case of a positive response in fewer than 75% of patients, and \"not effective\" if patients deteriorated or died following RF therapy. RF therapy was reported in 381 articles addressing 33 separate IMDs. A positive effect was established in MADD type 3 (n=536, 93.1% responsive), RTD 2,3 (n = 94, 90.4% responsive), ACAD 9 (n = 29, 75.9% responsive), and FAD transporter deficiency (n = 5, 100% responsive). The effect was uncertain in complex I and II deficiency, ethylmalonic encephalopathy, FAD synthase deficiency, glutaric aciduria type 1, L2 hydroxyglutaric aciduria, and MADD type 2. RF was not effective in MADD type 1. Adverse effects were infrequent and mild. RF therapy in MADD type 3, RTD 2 and 3, ACAD9, and FAD transporter deficiency is safe and effective. Access to RF for these patients is crucial. For a substantial group of IMDs, the effect of RF remains uncertain. In these conditions, a trial of RF therapy with clearly defined outcome criteria might be considered.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":"e70190"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13122134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773941","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":"Short-Term Oral Spermidine Supplementation Modifies Aspects of Neurodegenerative Disease in Flies and Mice With MPS III.","authors":"Helen Beard, Sonia Dayan, Karissa Barthelson, Laura Hewson, Louise V O'Keefe, Kim M Hemsley","doi":"10.1002/jimd.70195","DOIUrl":"10.1002/jimd.70195","url":null,"abstract":"<p><p>Mucopolysaccharidosis type III (MPS III) is a group of autosomal recessive neurodegenerative lysosomal storage disorders that causes progressive cognitive and physical impairment, predominantly in child/early adulthood. The median age of death is 17 years as there is no safe, effective treatment approved. Using faithful Drosophila and murine models of MPS III, we have characterised the MPS IIIA and MPS IIIC fly metabolome, explored the ability of oral spermidine supplementation to ameliorate clinical disease in the fly models and explored its mechanism of action in MPS IIIA mice. Spermidine is a polyamine naturally synthesised by the body. Its manufacture decreases with age. Supplementation has been reported to stimulate autophagy, reduce cell senescence and increase health/lifespan. The metabolomic evaluation confirmed that whole MPS IIIA and MPS IIIC flies exhibit a progressively deranged metabolome. Significantly up-regulated metabolites were those involved in nucleotide and purine metabolism. The most significantly down-regulated metabolites were those involved in ascorbate and aldarate metabolism. Further, spermidine levels decreased significantly in all fly genotypes with age. In short-term studies, food enriched with 5 mM spermidine improved overall fly activity and climbing ability. A 4-week study in pre-symptomatic MPS IIIA mice (3- or 6-mM spermidine, supplemented in drinking water) revealed no improvement in microgliosis or lysosomal compartment size; however, we observed a significant reduction in the astroglial response in the brain, which is believed to drive disease progression. Longer-term confirmatory studies in larger cohorts of MPS III animals are now warranted to determine whether spermidine supplementation is of benefit in preventing or slowing clinical disease in this and other childhood dementias.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":"e70195"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13125739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773891","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":"Natural History of Morquio A Syndrome.","authors":"Shunji Tomatsu, Kimberly Klipner, Marie Sahou, Jacky M Guerrero-Vargas, Stuart Mackenzie, Lauren Averill, Heidi Kecskemethy, Yasuhiko Ago, Shaukat Khan, Chris Church, Melissa A Alderfer, Thomas H Shaffer, Tariq Rahman, Abraham Oommen, Claude Beaty, Emi H Caywood, Ayaka Silverman, Takeshi Tsuda, Jobayer Hossain, Lan He","doi":"10.1002/jimd.70199","DOIUrl":"10.1002/jimd.70199","url":null,"abstract":"<p><p>Mucopolysaccharidosis IVA (Morquio A) is a progressive lysosomal disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase, resulting in the accumulation of glycosaminoglycans, primarily in cartilage and bone. The condition leads to skeletal dysplasia, impaired ossification, and growth imbalance, causing cervical compression, tracheal obstruction, hip dysplasia, and cardiopulmonary complications. Although existing natural history studies have clarified several aspects of disease progression, objective methods to quantify skeletal pathology and its functional impact remain limited. Standard endurance-based assessments, including the 6-min walk test, 3-min stair climb, and spirometry, are variable and infeasible for young children, wheelchair-dependent individuals, or patients with respiratory or postoperative limitations. Their dependence on motivation, training, and site-specific differences restricts their value as reliable endpoints. Significant gaps persist in the objective evaluation of skeletal dysplasia progression and its functional impact. There remains an unmet need for non-invasive, quantitative tools that capture multisystem involvement across the full phenotypic spectrum. Objective tools exist as we reported but have not been widely implemented or standardized, and data supporting their use as regulatory endpoints remain limited. Emerging longitudinal, multidisciplinary evaluations and surrogate biochemical biomarkers show potential to define disease severity, support prognosis, and serve as validated endpoints for therapeutic monitoring and surgical risk stratification. In conclusion, to address the limitations of prior studies, we propose a novel natural history program of innovative, non-invasive assessments based on our compiled data. Such approaches may contribute to more consistent longitudinal data and help inform the development of clinical endpoints for emerging therapies.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":"e70199"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367501/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147964045","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":"Real-Life Application of a Point-of-Care Biosensor for Phenylalanine in Patients With Phenylketonuria.","authors":"Corentin Gondrand, Anna T Reischl-Hajiabadi, Estelle Bonedeau, Nicolas Weiß, Gerd Schneider, Maurice Fahn, Frederic Myers, Philipp Minel Städle, Kathrin Jeltsch, Georg F Hoffmann, Jürgen G Okun, Dorothea Haas, Sven F Garbade, Kai Johnsson, Thomas Opladen","doi":"10.1002/jimd.70187","DOIUrl":"10.1002/jimd.70187","url":null,"abstract":"<p><p>Phenylketonuria (PKU) is a rare metabolic disorder causing elevated phenylalanine (PHE) levels requiring lifelong dietary or pharmacological management and regular monitoring. Current PHE monitoring methods, such as tandem mass spectrometry (FIA-MS/MS), are laboratory and sample transport-dependent, leading to delays in obtaining results. This highlights the need for accessible point-of-care (PoC) solutions. Building on a previously developed bioluminescence-based PHE quantification method, we created a PoC PHE sensor integrated with a smartphone app (phenyx app) for real-time monitoring and data sharing. In a clinical study with PKU patients, we evaluated the reliability of the sensor and the app by comparing at-home PHE measurements with dried blood samples (DBS) analyzed using the gold standard FIA-MS/MS. We also assessed time differences between sampling and results, sensor practicality, and user experience. Forty-seven PKU patients (median age 10.0 years, range 0.7-53.4) performed one supervised and four at-home measurements using the PHE sensor, alongside DBS sampling for FIA-MS/MS. The sensor showed higher PHE values than FIA-MS/MS, with a mean difference of 84.8 μmol/L (p = 0.0017). Variability was influenced by test supervision (clinic vs. home) and test kit age (greater difference in older batches, p = 0.001). Usability of the PHE sensor and phenyx app was rated favorably; all patients preferred the PHE sensor over laboratory testing. PoC measurement using the PHE sensor and phenyx app is feasible, reliable, and provides rapid results comparable to FIA-MS/MS, representing a key step toward patient self-testing. Trial Registration: NCT05998109, NCT06940193, DRKS00031972.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":"e70187"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698918","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":"Aminoacyl-tRNA Synthetases: Variant Classification, Functional Assays, and Emerging Therapeutic Strategies.","authors":"M I Mendes, D E Smith, V Spek, A M Bosch, W E Corpeleijn, M Engelen, S A Fuchs, A Hadchouel, I U Heinemann, R H Houtkooper, E M M Hoytema van Konijnenburg, S Kemp, M Langeveld, C D M Karnebeek, A Pop, V M Siu, N I Wolf, G S Salomons","doi":"10.1002/jimd.70184","DOIUrl":"10.1002/jimd.70184","url":null,"abstract":"<p><p>Aminoacyl-tRNA synthetases (aaRS) are essential enzymes that charge tRNAs with their corresponding amino acids, playing a critical role in protein synthesis. All 37 nuclear-encoded ARS genes, comprising both cytosolic (ARS1) and mitochondrial (ARS2) isoforms, have now been linked to human disease. Pathogenic variants in these genes cause a wide range of phenotypes, from dominant peripheral neuropathies to recessive multisystemic disorders. Despite the high number of ARS variants identified, functional validation remains difficult, with over 80% of missense variants classified as VUS in public databases. Additionally, the role of non-canonical aaRS functions in disease remains an area requiring further exploration. Our laboratory developed a high-throughput LC-MS/MS-based aminoacylation assay to measure aaRS activity in patient-derived fibroblasts, aiding in variant classification. This functional approach has contributed to the diagnosis of nearly 200 patients and has uncovered complex variant effects, including thermolabile and splicing-defective forms. Therapeutically, amino acid supplementation and dietary interventions have shown effect in select cases, while gene therapy is being explored for dominant ARS-related neuropathies. Amenability to targeted interventions further underlines the need for correct interpretation of genetic variants, which are increasingly recognized as genetic testing is progressively used in the diagnostic work-up and functional assays. Additionally, natural history studies are essential to improve diagnosis, understand disease mechanisms, and guide and evaluate personalized treatment. This review underscores the critical need for integrated genomic and functional approaches to advance variant interpretation and therapeutic development in the era of NGS.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":"e70184"},"PeriodicalIF":3.8,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13107504/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147773771","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148094863","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148094864","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093947","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":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148093945","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}