Journal of Inherited Metabolic Disease最新文献

{"title":"Personalized Genotype-Based Approach for Treatment of Phenylketonuria","authors":"Polina Gundorova,&nbsp;Behnam Yousefi,&nbsp;Mathias Woidy,&nbsp;Malcolm Summer Rose-Heine,&nbsp;Robin Khatri,&nbsp;Viviane Kasten,&nbsp;Stefan Bonn,&nbsp;Ania Carolina Muntau,&nbsp;Soeren Waldemar Gersting","doi":"10.1002/jimd.70067","DOIUrl":"https://doi.org/10.1002/jimd.70067","url":null,"abstract":"<p>Extensive studies have examined the clinical manifestations, pathogenic mechanisms, and genetic variations of phenylketonuria (PKU) across different populations, resulting in a substantial collection of molecular genetic data on the phenylalanine hydroxylase (<i>PAH</i>) gene and its variants. However, many genotypes are associated with a range of clinical phenotypes, as well as variable responsiveness to sapropterin, presenting ongoing challenges for effective treatment. To address this, we enhanced the PAH activity landscapes method by incorporating high-throughput techniques, including automated pipetting, integrated data processing via Gaussian modeling of 3D surfaces, and bioinformatics analyses with robust quality control. Using PAH activity landscapes, we visualized PAH enzymatic function across 99 common <i>PAH</i> genotypes under varying metabolic and therapeutic conditions. This deep functional phenotyping approach enabled us to identify distinct genotype subpopulations by using consensus clustering, correlate them with clinical phenotypes, and propose subpopulation-specific treatment protocols. Our findings suggest that clinical phenotypes can be predicted and treatment regimens can be adjusted based on residual PAH function profiles. To further support personalized treatment strategies, we revised our publicly accessible <i>PAH genotype &amp; activity landscapes database</i> to share the latest insights into PAH function and patient phenotypes—namely residual enzyme activity and responsiveness to sapropterin as conveyed by two alleles. This resource underscores the translational significance of functional research in PKU and offers a practical tool to support personalized treatment in clinical settings.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725598","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":"Myopathic Symptoms and Exercise Tolerance in Adolescent Patients With Long-Chain Fatty Acid Oxidation Disorders","authors":"Marit Schwantje,&nbsp;Marco van Brussel,&nbsp;Tim Takken,&nbsp;Monique G. M. de Sain-van der Velden,&nbsp;Mirjam Langeveld,&nbsp;Gepke Visser,&nbsp;Sabine A. Fuchs","doi":"10.1002/jimd.70070","DOIUrl":"https://doi.org/10.1002/jimd.70070","url":null,"abstract":"<p>Long-chain fatty acid oxidation disorders are characterized by rhabdomyolysis, often provoked by physical exercise. For the newborn screening (NBS) cohort, it remains uncertain to what extent they will develop the myopathic phenotype. This study assesses physiological responses to exercise, muscle symptoms, and activity levels in 14 adolescent lcFAOD patients (VLCADD (<i>n</i> = 8), LCHADD (<i>n</i> = 4), CPT2D (<i>n</i> = 1) and LCKATD (<i>n</i> = 1); ages 9.9–17.8 years). Analyses of incremental and prolonged cardiopulmonary exercise tests, a symptom-based questionnaire, and the Short Questionnaire to Assess Health-enhancing physical activity were performed. The results revealed a decreased ventilatory anaerobic threshold compared to control data (z-score − 0.5 (0.8) [median (interquartile range (IQR))], <i>p</i> = 0.001) and, on average, a decreased relative peak oxygen uptake (z-score − 1.3 (2.8), <i>p</i> = 0.005) and relative peak work rate (z-score − 0.7 (1.3), <i>p</i> = 0.03). There were no adverse events during and following prolonged exercise under well-fed circumstances (based on symptoms and post-exercise creatine kinase). The symptom-based questionnaire revealed that the presence of provoking factors (e.g., infection, inadequate intake) increased the risk of rhabdomyolysis during/after exercise. Screening (<i>n</i> = 11) and symptomatically (<i>n</i> = 3) diagnosed patients showed normal levels of physical activity (medians: 3.5 h per week) compared to their healthy peers (3.2 h), despite debilitating muscle pain in 46% of the by screening and all of the symptomatically diagnosed patients. In conclusion, patients with seemingly normal exercise patterns reported debilitating muscle symptoms and rhabdomyolysis, especially when additional provoking factors were present. Exercise tests may provide a valuable tool to monitor and guide exercise potential in these new NBS cohorts.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70070","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725597","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":"Exploring Exhaled Breath Analysis in Adults With Chronic Visceral Acid Sphingomyelinase Deficiency to Identify Potential Biomarkers of Pulmonary Involvement","authors":"Eline C. B. Eskes,&nbsp;Bauke V. Schomakers,&nbsp;Michel van Weeghel,&nbsp;Suzanne W. J. Terheggen-Lagro,&nbsp;Lilian J. Meijboom,&nbsp;Carla E. M. Hollak,&nbsp;Paul Brinkman,&nbsp;Barbara Sjouke","doi":"10.1002/jimd.70039","DOIUrl":"https://doi.org/10.1002/jimd.70039","url":null,"abstract":"<p>Acid sphingomyelinase deficiency (ASMD) is a rare lysosomal storage disease. The most commonly affected organs are the spleen, the liver, and the lungs. Pulmonary involvement resembles interstitial lung disease and often leads to decreased diffusion capacity of the lungs for carbon monoxide (DLCO). An emerging technique in pulmonary research is the analysis of exhaled breath. The aim of this study was to investigate potential markers of pulmonary involvement in the exhaled breath of adult chronic visceral ASMD patients and to quantify findings on high-resolution computed tomography (HRCT) of the lungs in order to be able to correlate HRCT findings with (the potential) markers for pulmonary involvement. Fifteen adult, chronic visceral ASMD patients and 34 age-, sex-, and smoking habit-matched healthy controls were recruited and provided two different types of exhaled breath samples: exhaled air and exhaled condensate. Additionally, pulmonary function testing was performed for both patients and healthy controls, and HRCT of the lungs and biochemical markers were available for patients. Exhaled breath samples were analyzed using gas and liquid chromatography-mass spectrometry (GC–MS and LC–MS respectively). Fifteen compounds of interest were identified based on significant differences between ASMD patients and healthy controls, of which the most promising were 2-hydroperoxyhexane, 6-heptyn-2-one, and 4-pentenyl acetate. Other compounds have been described in the context of systemic sclerosis (i.e., acetophenone) or lung cancer (i.e., benzaldehyde and dodecane). Some markers were associated with the pathophysiological process of lipid peroxidation (i.e., decane, dodecane and 2-methylnonane). SPLSDA and AUROCC analyses showed that the model was better able to distinguish the patients with pulmonary involvement from their matched controls than all patients from all controls. Lastly, a quantitative HRCT score was performed and correlated with patients' DLCO (R = −0.74, <i>p</i> = 0.006). The most promising markers based on our analyses (i.e., 2-hydroperoxyhexane, 6-heptyn-2-one and 4-pentenyl acetate) have not been described in previous studies in the pulmonary field and might be ASMD-specific.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144714865","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":"Long-Term Efficacy and Tolerability of Pegzilarginase in Arginase 1 Deficiency: Results of Two International Multicentre Open-Label Extension Studies","authors":"Markey McNutt,&nbsp;Frank Rutsch,&nbsp;Rossana Sanchez Russo,&nbsp;Serena Gasperini,&nbsp;Spyros Batzios,&nbsp;Elisa Leão Teles,&nbsp;Anaïs Brassier,&nbsp;Jaya Ganesh,&nbsp;Andreas Schulze,&nbsp;Gregory M. Enns,&nbsp;Mattias Rudebeck","doi":"10.1002/jimd.70066","DOIUrl":"https://doi.org/10.1002/jimd.70066","url":null,"abstract":"<p>Arginase 1 deficiency (ARG1-D) is an autosomal recessive urea cycle disorder characterised by chronic hyperargininaemia, progressive spasticity, loss of mobility, and cognitive dysfunction. Standard of care (SOC), based on dietary protein restriction, rarely prevents progression. Pegzilarginase, a recombinant human enzyme, is the first approved disease-modifying therapy. We report outcomes from Study 102A (<i>n</i> = 14; up to 5 years) and the PEACE long-term extension (LTE) (<i>n</i> = 31; up to 3 years). Weekly pegzilarginase was administered with SOC. Outcomes included functional mobility (2-/6-minute walk tests [2MWT/6MWT], Gross Motor Function Measure [GMFM] D/E), spasticity (Modified Ashworth Scale [MAS]), plasma arginine, guanidino compounds, and safety. In PEACE, LTE arms were named according to initial 24-week double-blind treatment: placebo–pegzilarginase or pegzilarginase–pegzilarginase. Of 39 evaluable participants, 37 (95%) met composite response or achieved maximum score in ≥ 1 motor function domain. In 102A, mean 6MWT improved to 68.2 m (+19%; <i>n</i> = 12); GMFM-D/E increased by 2.7/3.7. In PEACE (pegzilarginase–pegzilarginase; placebo–pegzilarginase), 2MWT improved to 16.5 m (+25%; <i>n</i> = 6) and 13.5 m (+16%; <i>n</i> = 2); GMFM-D/E improved by 4.3/6.0 (<i>n</i> = 6) and 5.3/11.3 (<i>n</i> = 3). Spasticity improved in 21/25 (84%), with 12 reaching MAS 0 (no spasticity). Pegzilarginase sustained plasma arginine control: in 102A, means were 118 μmol/L at Week 192 (<i>n</i> = 9); in PEACE, &lt; 115 μmol/L through Week 96 (<i>n</i> = 11). Guanidinoacetic acid normalised; N-acetylarginine approached normal; argininic acid and α-keto-δ-guanidinovaleric acid declined by &gt; 50%. Most adverse events were mild/moderate; no treatment-related discontinuations or persistent antibodies occurred. Pegzilarginase produced sustained improvements in mobility, spasticity and biochemical control, supporting early intervention, long-term use and disease modification in ARG1-D.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70066","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705609","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":"Therapies for Mitochondrial Disease: Past, Present, and Future","authors":"Megan Ball,&nbsp;Nicole J. van Bergen,&nbsp;Alison G. Compton,&nbsp;David R. Thorburn,&nbsp;Shamima Rahman,&nbsp;John Christodoulou","doi":"10.1002/jimd.70065","DOIUrl":"https://doi.org/10.1002/jimd.70065","url":null,"abstract":"<p>Mitochondrial disease is a diverse group of clinically and genetically complex disorders caused by pathogenic variants in nuclear or mitochondrial DNA-encoded genes that disrupt mitochondrial energy production or other important mitochondrial pathways. Mitochondrial disease can present with a wide spectrum of clinical features and can often be difficult to recognize. These conditions can be devastating; however, for the majority, there is no targeted treatment. In the last 60 years, mitochondrial medicine has experienced significant evolution, moving from the pre-molecular era to the Age of Genomics in which considerable gene discovery and advancement in our understanding of the pathophysiology of mitochondrial disease have been made. In the last decade, in response to the urgent need for effective treatments, a wide range of emerging therapies have been developed, driven by innovative approaches addressing both the genetic and cellular mechanisms underpinning the diseases. Emerging therapies include dietary intervention, small molecule therapies aimed to restore mitochondrial function, stem cell or liver transplantation, and gene or RNA-based therapies. However, despite these advances, translation to clinical practice is complicated by the sheer genetic and clinical complexity of mitochondrial disease, difficulty in efficient and precise delivery of therapies to affected tissues, rarity of individual genetic conditions, lack of reliable biomarkers and clinically relevant outcome measures, and the dearth of natural history data. This review examines the latest developments in the pursuit to identify effective treatments for mitochondrial disease and discusses the barriers impeding their success in translation to clinical practice. While treatment for mitochondrial disease may be on the horizon, many challenges must be addressed before it can become a reality.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 4","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70065","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705608","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":"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":"<p>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.</p><p>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 [<span>1</span>]. 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.</p><p>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 [<span>2</span>]. 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 [<span>2</span>]. 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 [<span>3</span>]. 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.</p><p>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}