Journal of Inherited Metabolic Disease最新文献

{"title":"Current Understanding of Pathogenic Mechanisms and Disease Models of Citrin Deficiency","authors":"Denis Lacabanne,&nbsp;Alice P. Sowton,&nbsp;Bosco Jose,&nbsp;Edmund R. S. Kunji,&nbsp;Sotiria Tavoulari","doi":"10.1002/jimd.70021","DOIUrl":"https://doi.org/10.1002/jimd.70021","url":null,"abstract":"<p>Citrin deficiency (CD) is a complex mitochondrial disease with three different age-related stages: neonatal intrahepatic cholestasis caused by CD (NICCD), failure to thrive and dyslipidemia caused by CD (FTTDCD), and type II citrullinemia (CTLN2), recently renamed adolescent and adult CD (AACD). While highly prevalent in the Asian population, CD is pan-ethnic and remains severely underdiagnosed. The disease is caused by the dysfunction or absence of the mitochondrial aspartate/glutamate carrier 2 (AGC2/SLC25A13), also known as citrin. Citrin deficiency results in a direct impairment of the malate–aspartate shuttle and the urea cycle, with expected knock-on effects on a multitude of other metabolic pathways, leading to a complicated pathophysiology. Here, we discuss our current knowledge of the molecular mechanism of substrate transport by citrin, including recent advances  suggesting against its calcium regulation. We also discuss the different types of pathogenic variants found in CD patients and new insights into their pathogenic mechanisms. Additionally, we provide a summary and assessment of the efforts to develop preclinical models as well as treatments for the disease.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707374","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":"Increased Survival in Patients With Molybdenum Cofactor Deficiency Type A Treated With Cyclic Pyranopterin Monophosphate","authors":"Guenter Schwarz,&nbsp;Donald G. Basel,&nbsp;Bernd C. Schwahn,&nbsp;Ronen Spiegel,&nbsp;Flora Y. Wong,&nbsp;Robin Bliss,&nbsp;Liza Squires","doi":"10.1002/jimd.70000","DOIUrl":"https://doi.org/10.1002/jimd.70000","url":null,"abstract":"<p>Molybdenum cofactor deficiency (MoCD) Type A is an ultrarare disorder causing neurodegeneration and early death. Cyclic pyranopterin monophosphate (cPMP), a molybdenum cofactor precursor, is a therapeutic option for patients with MoCD Type A. In this study, efficacy in patients with MoCD Type A treated with recombinant cPMP (rcPMP) and/or fosdenopterin, a synthetic form of cPMP, from one retrospective and two prospective open-label studies (<i>N</i> = 14), was compared with a retrospective/prospective natural history study (untreated; <i>N</i> = 37). Safety was evaluated in treated patients. Patients treated with fosdenopterin/rcPMP had significantly reduced risk of premature/early death versus untreated patients (Cox proportional hazards 5.1; 95% CI 1.32–19.36; <i>p</i> = 0.01). MoCD disease biomarkers of urinary S-sulfocysteine and xanthine returned to near-normal from baseline to last visit in treated patients but remained abnormal in untreated patients. At 12 months, in treated patients, 43% could sit unassisted, 44% were ambulatory, and 57% could feed orally. Initiating fosdenopterin/rcPMP treatment ≤ 14 days after birth appeared to result in better clinical outcomes than initiating &gt; 14 days after birth. Most patients (13/14) had a treatment-emergent adverse event; most were unrelated to fosdenopterin/rcPMP, were mild to moderate in severity, and none led to treatment discontinuation. These results demonstrate that patients with MoCD Type A who received fosdenopterin/rcPMP versus untreated patients were more likely to survive. Some treated patients were able to feed orally and achieve developmental milestones including walking. Fosdenopterin/rcPMP was generally well-tolerated. Improved outcomes in patients treated early support the importance of identifying MoCD in neonates and initiating treatment as soon as possible.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70000","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698979","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 “Clinical Outcomes in Patients Switching From Agalsidase Beta to Migalastat: A Fabry Registry Analysis”","authors":"","doi":"10.1002/jimd.70023","DOIUrl":"https://doi.org/10.1002/jimd.70023","url":null,"abstract":"<p>A. Pisani, K. M. Wilson, J. L. Batista, et al., “Clinical Outcomes in Patients Switching from Agalsidase Beta to Migalastat: A Fabry Registry Analysis,” <i>Journal of Inherited Metabolic Disease</i> 47, no. 5 (2024): 1080–1095, https://doi.org/10.1002/jimd.12773.</p><p><i>Note:</i> For each outcome, the model includes patients with at least 1 record in each of the pre- and post-switch periods; sample sizes are the same as those shown for Classic and Late-onset patients in Table 2. Each model includes interaction terms to allow slopes to vary by time period (pre/post switch) and phenotype, is adjusted for age at switch date (continuous) and sex, and includes random intercepts. To visually display estimated trajectories over time for each phenotype, estimated values are shown for a male, aged 50 years at the switch date. The slopes of the lines indicate the estimated annual change in the outcome during each time period. Estimated slopes are the same regardless of sex or age.</p><p>We apologize for this error.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698980","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":"Never-Treated, Non Splenectomised Patients With Gaucher Disease (The French GANT Study): The Prospective Follow-Up","authors":"Alberto Nasce,&nbsp;Yann Nguyen,&nbsp;Nadia Belmatoug,&nbsp;Karima Yousfi,&nbsp;Fabrice Camou,&nbsp;Magali Pettazzoni,&nbsp;Florence Dalbies,&nbsp;Bérengère Cador,&nbsp;Anaïs Brassier,&nbsp;Samia Pichard,&nbsp;Bénédicte Hivert,&nbsp;Laure Swiader,&nbsp;Ivan Bertchansky,&nbsp;Vanessa Leguy Seguin,&nbsp;Wladimir Mauhin,&nbsp;Leonardo Astudillo,&nbsp;Isabelle Hau Rainsard,&nbsp;Sébastien Humbert,&nbsp;Celia Hoebeke,&nbsp;Dalil Hamroun,&nbsp;Agathe Masseau,&nbsp;Marc G. Berger,&nbsp;Jérôme Stirnemann,&nbsp;Christine Serratrice,&nbsp;Comité d'Evaluation et de Traitement de la maladie de Gaucher (CETG)","doi":"10.1002/jimd.70026","DOIUrl":"10.1002/jimd.70026","url":null,"abstract":"<div>\u0000 \u0000 <p>Treatment options for Type 1 Gaucher Disease (GD1) include enzyme replacement therapy and oral substrate reduction therapy. The criteria for treatment initiation vary across regions. Recent retrospective studies have highlighted the natural progression of never-treated GD1, suggesting that some patients remain asymptomatic or stable for extended periods. However, there is no data on long-term prospective follow-up. We conducted a prospective study following a cross-sectional analysis of 36 never-treated, non-splenectomised GD1 patients from the French Gaucher Disease Registry (FGDR). The objective was to describe the natural disease progression, tracking clinical, radiological, and biological characteristics over time. Thirty-six non-splenectomised and never-treated patients (19 women and 17 men) diagnosed with Gaucher Disease were prospectively followed for an additional median duration of 6.5 (5–8.3) years. Of the cohort, 17 remained untreated, 10 initiated treatment, and 7 were lost to follow-up. Although never-treated patients tended to be older at the time of first symptoms, diagnosis, and last follow-up compared to those who received treatment, the difference was not significant in this small cohort. At last follow-up, never-treated patients had no worsening of most of their symptoms. No significant changes were observed in platelets, chitotriosidase, and lyso-Gb1. In this prospective cohort, we highlight that patients with mild GD can remain untreated with no disease progression, offering insights into cost-effective management strategies. Identifying such patients is still challenging.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663656","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":"Glycerophospholipids: Roles in Cell Trafficking and Associated Inborn Errors","authors":"Foudil Lamari,&nbsp;Francis Rossignol,&nbsp;Grant A. Mitchell","doi":"10.1002/jimd.70019","DOIUrl":"https://doi.org/10.1002/jimd.70019","url":null,"abstract":"<p>Glycerophospholipids (GPLs) are the main lipid components of cellular membranes. They are implicated in membrane structure, vesicle trafficking, neurotransmission, and cell signalling. GPL molecules are amphiphilic, organized around the three carbons of glycerol. Positions <i>sn-1</i> and <i>sn-2</i> are each esterified to a fatty acid (FA). At position <i>sn-3</i>, a phosphate group is linked, which in turn can bind a polar head group, the most prevalent classes being phosphatidic acid (PA, phosphate alone as head group), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylinositol (PI), and cardiolipin (CL). Pathways of GPL biosynthesis span several cell compartments (endoplasmic reticulum (ER), Golgi mitochondria). Particularly important are mitochondria-associated membranes (MAMs), where the ER and mitochondrial outer membrane are in proximity. After synthesis, GPLs continuously undergo remodelling by FA hydrolysis and re-esterification. Esterification with different FAs alters membrane properties. Many steps in GPL synthesis and remodelling can be mediated by more than one enzyme, suggesting complexity that requires further exploration. The 38 known GPL-related inborn errors are clinically diverse. 23 (61%) have neurologic features, sometimes progressive and severe, particularly developmental delay/encephalopathy in 16 (42%) and spastic paraplegia in 12 (32%). Photoreceptor/neuroretinal disease occurs in 14 (37%). Three present skeletal dysplasias (8%). Most GPL inborn errors have been diagnosed by broad molecular testing. Lipidomics holds promise for diagnostic testing and for the discovery of functionally relevant metabolite profiles for monitoring natural history and treatment response.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70019","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645778","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 “Comparative Analysis of Gene and Disease Selection in Genomic Newborn Screening Studies”","authors":"","doi":"10.1002/jimd.70022","DOIUrl":"https://doi.org/10.1002/jimd.70022","url":null,"abstract":"<p>I. R. Betzler, M. Hempel, U. Mütze, et al., “Comparative Analysis of Gene and Disease Selection in Genomic Newborn Screening Studies,” <i>Journal of Inherited Metabolic Disease</i> 47, no. 5 (2024): 945–970, https://doi.org/10.1002/jimd.12750.</p><p>It has come to our attention that our original article contained errors in the mapping of ClinGen's Gene-Disease Validity data to gene lists from genomic newborn screening studies. Specifically, Table 2 mistakenly included the genes <i>MAGT1</i>, <i>CACNA1C</i>, <i>GJA1</i>, <i>KCNJ5</i>, <i>NOTCH3</i>, and <i>RASA1</i>, which were assigned to phenotypes primarily listed in ClinGen rather than those considered in the gNBS panels.</p><p>These corrections do not alter the overall conclusions of our study but clarify the challenges involved in defining target diseases for gNBS. We sincerely appreciate the constructive feedback from our colleagues and apologize for this error. We remain committed to transparency and accuracy in genomic newborn screening research.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143645779","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":"Performance of Relative Exchangeable Copper for the Diagnosis of Wilson Disease in Acute Liver Failure","authors":"Daniela Spirea,&nbsp;Claire Vanlemmens,&nbsp;François Parant,&nbsp;Teresa Antonini,&nbsp;Muriel Bost,&nbsp;Alain Lachaux,&nbsp;Abdelouahed Belmalih,&nbsp;Olivier Guillaud,&nbsp;Jerome Dumortier,&nbsp;Eduardo Couchonnal","doi":"10.1002/jimd.70024","DOIUrl":"https://doi.org/10.1002/jimd.70024","url":null,"abstract":"<p>Acute liver failure (ALF) can be one of the manifestations of Wilson disease (WD), and due to its severity, prompt diagnosis is essential. A ratio &gt; 15% of the exchangeable copper to total serum copper, known as relative exchangeable copper (REC), has been shown to have a 100% sensitivity and specificity for the diagnosis of WD but this has not yet been studied in an ALF setting. Patients diagnosed with ALF from 1 November 2011 to 31 December 2023, with available REC determination during the acute event, were included. Thirty-three patients were included (11 with WD and 22 without WD). The median age [IQR] at ALF was 12.9 [8.9–20.2] years, range: 0.6–71.0 years. Serum ceruloplasmin (Cp) &lt; 0.20 g/L and 24 h urinary copper excretion &gt; 1.6 μmol/L had both a sensitivity (Se) and specificity (Sp) for the diagnosis of WD of 100% and 72.7%, respectively. A ROC analysis of REC determined that the best cut-off point was 14.4% (AUC 1, <i>p</i> &lt; 0.01). All the WD patients had REC values &gt; 14.4%, yielding a sensitivity and specificity of 100. Relative exchangeable copper has 100% sensitivity and specificity for diagnosing Wilson disease in acute liver failure. Relative exchangeable copper has excellent performance in diagnosing Wilson disease in acute liver failure.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639064","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":"Safety and Efficacy of DTX401, an AAV8-Mediated Liver-Directed Gene Therapy, in Adults With Glycogen Storage Disease Type I a (GSDIa)","authors":"David A. Weinstein,&nbsp;Terry G. Derks,&nbsp;David F. Rodriguez-Buritica,&nbsp;Ayesha Ahmad,&nbsp;María-Luz Couce,&nbsp;John J. Mitchell,&nbsp;Rebecca Riba-Wolman,&nbsp;Malaya Mount,&nbsp;Julieta Bonvin Sallago,&nbsp;Katalin M. Ross,&nbsp;Melanie M. van der Klauw,&nbsp;Foekje de Boer,&nbsp;Caroline van der Schaaf,&nbsp;Heather Saavedra,&nbsp;Miguel Martínez-Olmos,&nbsp;Elvis Atanga,&nbsp;Asad Hosseini,&nbsp;Deepali Mitragotri,&nbsp;Eric Crombez","doi":"10.1002/jimd.70014","DOIUrl":"https://doi.org/10.1002/jimd.70014","url":null,"abstract":"<p>Glycogen storage disease type Ia (GSDIa) is a rare, life-threatening, inherited carbohydrate metabolism disorder caused by glucose-6-phosphatase (G6Pase) deficiency, which is essential for glycogenolysis and gluconeogenesis. GSDIa management includes a strict medically prescribed diet that typically includes daily uncooked cornstarch doses, including overnight, to maintain euglycemia. DTX401 is an investigational adeno-associated virus serotype 8 vector expressing the human <i>G6PC1</i> gene that encodes G6Pase. This open-label, phase 1/2, dose-escalation, 52-week gene therapy trial evaluated the safety and efficacy of a single DTX401 infusion in 12 adults with GSDIa (ClinicalTrials.gov Identifier: NCT03517085). Three participants in Cohort 1 received DTX401 2.0 × 10¹² genome copies (GC)/kg, and three participants each in Cohorts 2, 3, and 4 received 6.0 × 10¹² GC/kg. Corticosteroids were administered to mitigate vector‑induced inflammatory response. All participants experienced a treatment-emergent adverse event (TEAE) and a related TEAE. No participant experienced a dose-limiting toxicity, TEAE leading to study discontinuation, TEAE leading to death, or serious treatment-related TEAE. Mean (SD) time to hypoglycemia in minutes/gram of carbohydrate during a controlled fasting challenge was 5.0 (1.6) at baseline and 6.9 (2.7) at Week 52, a mean (SD) increase of 46% (72%). Mean total daily cornstarch intake was 284 g at baseline and 85 g at Week 52 in the 10 participants with available values at both time points, a mean (SD) total daily cornstarch intake reduction of 68% (20%); <i>p</i> &lt; 0.001. DTX401 showed a favorable safety and efficacy profile at Week 52. Participants in all cohorts showed significant cornstarch need reductions from baseline to Week 52.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595247","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":"Elevated Cerebrospinal Fluid Total Tau in Niemann-Pick Disease Type C1: Correlation With Clinical Severity and Response to Therapeutic Interventions","authors":"Niamh X. Cawley,&nbsp;Ruyu Zhou,&nbsp;Nicole M. Farhat,&nbsp;James Iben,&nbsp;Derek M. Alexander,&nbsp;Rachel A. Luke,&nbsp;Cameron J. Padilla,&nbsp;Hibaaq O. Mohamed,&nbsp;Orsolya K. Albert,&nbsp;Kendall P. Robbins,&nbsp;Samar Rahhal,&nbsp;An Dang Do,&nbsp;Elizabeth Berry-Kravis,&nbsp;Stephanie M. Cologna,&nbsp;Fang Liu,&nbsp;Forbes D. Porter","doi":"10.1002/jimd.70016","DOIUrl":"https://doi.org/10.1002/jimd.70016","url":null,"abstract":"<p>Niemann-Pick disease, type C1 (NPC1) is an inborn error of intracellular cholesterol transport. Impaired function of NPC1 leads to endolysosomal accumulation of unesterified cholesterol, which results in progressive neurodegeneration. Although the age of onset is variable, classical NPC1 is a pediatric disease. Identification of biomarkers that correlate with clinical phenotype and respond to therapeutic interventions will be essential for developing effective therapeutic interventions. Aβ peptides and Tau protein are primary components of amyloid plaques and neurofibrillary tangles, respectively, which are major pathological features in neurodegenerative disorders. Cerebrospinal fluid (CSF) levels of total Tau, a biomarker of axonal damage, were elevated ~3-fold (<i>p</i> &lt; 0.0001) in 106 individuals with Niemann-Pick disease, type C1, relative to age-appropriate comparison samples. Baseline CSF total Tau levels correlated with clinical measures of disease severity. Specifically, CSF total Tau levels decreased with increased age of neurological onset (<i>r</i>_<i>s</i> = −0.42, FDR adj. <i>p</i> &lt; 0.0001) and increased with increased Annual Severity Increment Score (<i>r</i>_<i>s</i> = 0.52, FDR adj. <i>p</i> &lt; 0.0001). Baseline CSF total Tau levels were decreased 40% (<i>p</i> = 0.0066) in individuals being treated with miglustat, and longitudinal analysis substantiated this observation with a 40% decrease (<i>p</i> &lt; 0.0001, 95% CI 32%–47.4%). Longitudinal analysis also showed a significant (<i>p</i> = 0.004) decrease of 19% (95% CI 7%–30%) in total Tau levels associated with intrathecal 2-hydroxypropyl-β-cyclodextrin therapy. These data show that CSF total Tau levels are significantly increased in individuals with NPC1, positively correlated with increased disease severity, and respond to therapeutic interventions.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595055","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":"The Therapeutic Future for Congenital Disorders of Glycosylation","authors":"I. J. J. Muffels,&nbsp;T. Kozicz,&nbsp;E. O. Perlstein,&nbsp;E. Morava","doi":"10.1002/jimd.70011","DOIUrl":"https://doi.org/10.1002/jimd.70011","url":null,"abstract":"<div>\u0000 \u0000 <p>The past decade, novel treatment options for congenital disorders of glycosylation (CDG) have advanced rapidly. Innovative therapies, targeting both the root cause, the affected metabolic pathways, and resulting manifestations, have transitioned from the research stage to practical applications. However, with novel therapeutic abilities, novel challenges await, specifically when it concerns the large number of clinical trials that need to be performed in order to treat all 190 genetic defects that cause CDG known to date. The present paper aims to provide an overview of how the CDG field can keep advancing its therapeutic strategies over the coming years with these challenges in mind. We focus on three important pillars that may shape the future of CDG: the use of disease models, clinical trial readiness, and the possibility to make individualized treatments scalable to the entire CDG cohort.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 2","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595053","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}