Journal of Inherited Metabolic Disease最新文献

{"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":"https://doi.org/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":"Self-Reported Health-Related Quality of Life (HRQoL) in Adults With Urea Cycle Disorders","authors":"Curtis R. Coughlin II,&nbsp;John Barber,&nbsp;Chaya N. Murali,&nbsp;Members of the Urea Cycle Disorders Consortium (UCDC),&nbsp;Greta Wilkening","doi":"10.1002/jimd.70183","DOIUrl":"10.1002/jimd.70183","url":null,"abstract":"<p>Multiple studies have assessed Health-Related Quality of Life (HRQoL) in children with urea cycle disorders (UCDs); investigations in adults with the same disorders are rarer. Understanding the variables that modify self-reported HRQoL has become increasingly important as novel treatments are developed, with clinically meaningful endpoints required to assess efficacy. This was an ambispective study of participants enrolled in the Longitudinal Study of Urea Cycle Disorders (NCT00237315) conducted by the Urea Cycle Disorders Consortium (UCDC). Inclusion criteria included age ≥ 18 years and at least one completion of one of five HRQoL patient-reported outcome measures (PROMs). A total of 144 participants met inclusion criteria. Covariates included age at last assessment, sex at birth, specific UCD subtype, symptomatic status, treatments, and disease severity<i>.</i> The enrollees' self-reported HRQoL <i>T</i>-scores were not significantly different from the normative population. Whereas participants categorized as asymptomatic differed from those categorized as symptomatic in terms of disease severity, age at last HRQoL, and full-scale IQ, overall HRQoL did not differ. A model including age, sex, specific UCD subtype, symptomatic status, and disease severity revealed that perceived cognitive function was related to specific UCD subtype, while Anxiety and Emotional and Behavioral Dyscontrol were associated with sex at birth. When post-liver transplant participants were excluded, the pattern of associations was unchanged. Among adults with UCDs, responses on HRQoL measures revealed no significant differences in HRQoL when compared to normative populations. Cognitive reserve did not moderate the impact of diagnosis or treatment. Additional work in understanding and measuring HRQoL in this population is required.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639100","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":"Diagnostic Accuracy of Exchangeable Copper for Grading the Severity of Wilson Disease","authors":"Clément Desjardins,&nbsp;Nouzha Oussedik-Djebrani,&nbsp;Mickael Alexandre Obadia,&nbsp;Djamila Rahli,&nbsp;Chloé Le Cossec,&nbsp;France Woimant,&nbsp;Dominique Debray,&nbsp;Aurélia Poujois","doi":"10.1002/jimd.70178","DOIUrl":"10.1002/jimd.70178","url":null,"abstract":"<div>\u0000 \u0000 <p>Wilson disease (WD) diagnosis remains challenging due to variable biomarker performance across clinical presentations. Exchangeable copper (CuEXC) directly quantifies non-ceruloplasmin-bound copper (NCC), the pathogenic copper fraction. We assessed the diagnostic accuracy of CuEXC across WD phenotypes and its utility for evaluating disease severity. In this prospective study (NCT05231876) at the French National Reference Center for WD, we enrolled 158 treatment-naïve patients (48% female; mean age 20 ± 14 years; 44% ≤ 18 years) referred between 2009 and 2025. Clinical presentations included asymptomatic (<i>n</i> = 11), hepatic (<i>n</i> = 87), and neurologic (<i>n</i> = 60). CuEXC was measured at diagnosis and compared against ceruloplasmin, total copper, relative exchangeable copper (REC), and 24-h urinary copper using ROC analysis. Seven patients with hemolytic anemia uniformly associated with acute liver failure had extreme CuEXC elevations (median 11.0 μmol/L) and were excluded from ROC analyses. CuEXC increased stepwise across phenotypes (0.8, 1.6, and 2.9 μmol/L; <i>p</i> &lt; 0.001). CuEXC distinguished advanced from mild-to-moderate liver disease (AUC 0.86; 95% CI, 0.82–0.89; optimal threshold 1.8 μmol/L: sensitivity 83%, specificity 87%) and differentiated neurologic from hepatic presentations (AUC 0.87; 95% CI, 0.80–0.93; optimal threshold 2.07 μmol/L: sensitivity 88%, specificity 81%; pragmatic cutoff 2.0 μmol/L: sensitivity 91%, specificity 80%). Performance was consistent across age groups. CuEXC outperformed other biomarkers in head-to-head comparisons. After excluding hemolysis, CuEXC ≥ 1.8 μmol/L supports screening for advanced liver disease, even without clinical or laboratory liver abnormalities. CuEXC ≥ 2.0 μmol/L warrants expedited neurologic assessment and may help distinguish neuro Wilson from hepatic encephalopathy. CuEXC enhances early risk stratification for timely intervention in WD.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639094","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":"Caregiver Reports of Neurodevelopmental Functions in Pediatric Lysosomal Storage Disorders: A Scoping Review","authors":"Eileen M. Gillan,&nbsp;Beth Leiro,&nbsp;Amanda Nagy,&nbsp;Florian Eichler,&nbsp;Elise L. Townsend","doi":"10.1002/jimd.70179","DOIUrl":"10.1002/jimd.70179","url":null,"abstract":"<div>\u0000 \u0000 <p>Caregiver-reported outcome measures (CROMs) complement clinical assessments of neurodevelopmental functions (NDF) in pediatric rare disease trials. This scoping review summarizes use of CROMs of NDF across bodily function, activity, and participation domains of the International Classification of Functioning, Disability, and Health (ICF) model in pediatric lysosomal storage disorders (LSDs), characterizes assessed neurodevelopmental domains, and outlines considerations for CROM selection within a comprehensive functional assessment strategy. We applied JBI methodology and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Primary articles reporting CROM of NDF use in children with LSDs ≤ 12 years old were identified. Study characteristics, design, and CROMs utilized were extracted. CROMs were classified as condition-general or disease-specific. CROM content was mapped to neurodevelopmental domains (activities of daily living [ADL], cognition, communication, physical, social–emotional function). Ninety-eight articles published in the last 10 years reported on 38 distinct CROMs of NDF across &gt; 20 LSDs. Nearly all studies (93%) used ≥ 1 condition-general CROM of NDF, most commonly the Vineland Adaptive Behavioral Scales or the Pediatric Quality of Life Inventory. Eleven disease-specific CROMs were reported, typically alongside condition-general measures. Physical, ADL, and social–emotional domains were indexed most consistently. CROMs were endpoints in 32 LSD clinical trials. Findings illustrate the variety and common trends of CROMs of NDF used in pediatric LSD studies. This review informs selection of complementary caregiver-reported endpoints in LSD trials based on a well-defined, clinically meaningful construct; alignment with other endpoints and expert consensus; and operational practicality.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627926","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":"A Novel Multimodal LC–MS/MS Panel for the Comprehensive Diagnosis of Neurometabolic Disorders in CSF","authors":"Stine Christ,&nbsp;Julia Rossmann,&nbsp;Sylvia Richter,&nbsp;Sven Garbade,&nbsp;Glynis Klinke,&nbsp;Nenad Blau,&nbsp;Georg Friedrich Hoffmann,&nbsp;Jürgen Günther Okun,&nbsp;Thomas Opladen","doi":"10.1002/jimd.70167","DOIUrl":"10.1002/jimd.70167","url":null,"abstract":"<p>Metabolic testing of cerebrospinal fluid (CSF) is essential for early diagnosis of neurometabolic disorders. However, the large number of differential diagnoses, the phenotypic variance within a clinical picture, and the disease rarity complicate targeted metabolic diagnostics. To improve diagnosis the aim is to establish a liquid chromatography–tandem mass spectrometry (LC–MS/MS) based CSF panel (NeuroMetabolom) which enables a quick, reliable, extensive and cheap method requiring small amounts of analysis material replacing classical single platform analyses. The novel LC–MS/MS NeuroMetabolom method enables measuring all known standard metabolites in CSF, including purines/pyrimidines, sepiapterin, γ-Aminobutyric acid (GABA), and vitamin B₆ metabolites, with significantly reduced sample volume and measurement time. Due to their different biochemical interactions several runs with different sample preparation, running time and columns are necessary within the LC–MS/MS. Age-dependent reference values have been established. Positive controls with consistently detectable metabolite patterns were used to assess analytical reliability. The method has been implemented into routine diagnostics practice. The LC–MS/MS panel enables a simple, comprehensive, and rapid diagnostic approach, reducing time to diagnosis and facilitating early initiation of treatment. Instead of 650 μL, only 250 μL CSF is now required and the analysis time for all metabolites is reduced from 280 to 65.3 min excluding preparation and setup time. Furthermore, the panel is adaptable and can be regularly expanded to include additional clinically relevant metabolites. The novel LC–MS/MS panel, together with a neurometabolomic approach, offers a promising avenue to timely clinical diagnosis.</p><p><b>Trial Registration:</b> German Clinical Trials Register: DRKS00007878</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13053135/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627964","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":"Metabolism Controls the Timing of Human Brain Development and Maturation","authors":"Valentina Rava,&nbsp;Erica Cannone,&nbsp;Maura Francolini,&nbsp;Elena Taverna","doi":"10.1002/jimd.70180","DOIUrl":"10.1002/jimd.70180","url":null,"abstract":"<p>Among primates the human brain is the largest in size, exhibiting a higher neuronal density and connectivity. The prolonged expansion and subsequent connectome reorganization of the human brain have been suggested to promote higher cognitive and behavioral abilities. The notable variations in cognitive functions between human and nonhuman primates do not exclusively reside in neuronal abundance and connectivity but are also linked to a higher complexity in glial cells' morphology and functions at earlier time points, during embryonic brain development. Here we discuss two features of the human brain and their reciprocal connection. One feature is the high metabolic need of the developing and adult human brain. The other is its prolonged maturation, also known as neoteny. Even though the human brain occupies only a small percentage of the body mass, it is the highest consumer of glucose and oxygen. Among all brain cells, neurons have a great energy demand. Comparative studies suggest that increased glucose consumption and energy metabolism are positively correlated with higher cognitive abilities in humans. In line with the essential role of metabolism as a regulator of brain functions, recent breakthrough works have uncovered the correlation between metabolism and the timing of brain and neuron maturation during evolution. In this review, we specifically focus on the role of time in the evolution of the human brain and its synapses, focusing on the involvement of tissue, cellular, and subcellular metabolism.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13033476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574336","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":"Heritability of Long-Term Complications in Classic Galactosemia","authors":"Olivia S. Garrett,&nbsp;Nicole H. Smith,&nbsp;David J. Cutler,&nbsp;Yuhan Wu,&nbsp;Ina Knerr,&nbsp;Doireann Pereira,&nbsp;M. Estela Rubio-Gozalbo,&nbsp;E. Naomi Vos,&nbsp;Megan Harrison,&nbsp;Kara Pappas,&nbsp;David Coman,&nbsp;Karolina M. Stepien,&nbsp;Daniela Karall,&nbsp;Julian Margreitter,&nbsp;Sabine Scholl-Bürgi,&nbsp;Madison A. Heisler,&nbsp;Christina Lam,&nbsp;Maria R. Mills,&nbsp;Emilia Bélanger,&nbsp;Andrea C. Yu,&nbsp;Judith L. Fridovich-Keil","doi":"10.1002/jimd.70181","DOIUrl":"10.1002/jimd.70181","url":null,"abstract":"<div>\u0000 \u0000 <p>As a group, patients with classic galactosemia (CG) demonstrate a high prevalence of long-term complications despite early detection and life-long dietary restriction of galactose, which is the current standard of care. Individual outcomes, however, vary widely. For decades, research teams have sought to identify potential environmental, metabolic, and/or galactose-1-phosphate uridylyltransferase (<i>GALT</i>) allelic differences that might explain this variability—with limited success. Among large cohorts, only severe brain-related disease in infancy has been associated with increased prevalence of complications, and only the presence of predicted or detected residual GALT activity has been associated with decreased prevalence. While significant, these factors fail to account for the majority of long-term outcome variability in CG. Here, we tested whether genetic factors, both inside and outside the <i>GALT</i> locus, might contribute to variability in speech/voice/language, cognitive, and/or motor outcomes among patients. Specifically, we compared outcomes among 66 sets of affected siblings who share both <i>GALT</i> genotype and genetic background, 54 unrelated CG patients who share <i>GALT</i> genotype (p.Gln188Arg/p.Gln188Arg) but not genetic background, and 52 unrelated CG patients who share neither <i>GALT</i> genotype nor genetic background. Heritability estimates for all three complications demonstrate substantial genetic contributions, with point estimates of 100% heritability for all three. Less than 8% of this heritability appears due to residual GALT activity from hypomorphic <i>GALT</i> alleles. Combined with prior data demonstrating clustering of all three outcomes, these results offer compelling evidence for the existence of genetic modifiers of developmental outcomes in CG beyond the <i>GALT</i> locus.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 3","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574371","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":"Dietary Protein Modulation, Gut Microbiota, and Metabolic Control in Methylmalonic Acidemia: A Prospective Longitudinal Study","authors":"Engin Köse,&nbsp;Berkay Yekta Ekren,&nbsp;Neslihan Doğulu,&nbsp;Furkan Yolcu,&nbsp;Cemil Can Eylem,&nbsp;Emirhan Nemutlu,&nbsp;Uğur Sezerman,&nbsp;Fatma Tuba Eminoğlu","doi":"10.1002/jimd.70172","DOIUrl":"10.1002/jimd.70172","url":null,"abstract":"<div>\u0000 \u0000 <p>Methylmalonic acidemia (MMA) is a rare inherited metabolic disorder caused by defective conversion of methylmalonyl-CoA to succinyl-CoA. Emerging evidence suggests that both dietary protein composition and intestinal microbiota influence metabolic stability and clinical outcomes. This study aimed to evaluate the effects of stepwise dietary modification and short-term metronidazole therapy on systemic and gut-derived metabolic profiles in MMA. In this prospective, longitudinal, single-center study, eight genetically confirmed MMA patients underwent four sequential phases: baseline mixed-protein diet (50% intact protein/50% medical formula), protein restriction, intact protein enrichment (80% intact protein/20% medical formula), and adjunctive metronidazole therapy (20 mg/kg/day, 10 days/month for 3 months). Plasma amino acids, urinary metabolites, stool microbiota (16S rRNA long-read sequencing), and untargeted/tandem metabolomic profiles were analyzed at each phase. Transition to an intact protein-enriched diet significantly reduced plasma leucine levels (<i>p</i> = 0.008) without affecting isoleucine or valine. Urinary methylmalonic acid, 3-hydroxypropionate, lactate, and pyruvate decreased, indicating improved propionyl-CoA clearance. Microbiota diversity progressively declined, accompanied by reductions in butyrate-producing genera (Novisyntrophococcus, Lacrimispora, Hespellia). Metronidazole further lowered urinary methylmalonic acid and 3-hydroxypropionate (<i>p</i> = 0.017 and <i>p</i> = 0.028), with parallel decreases in fecal 3-indolelactic acid and phytosphingosine, suggesting suppression of gut-derived propionate and tryptophan metabolism. Despite antibiotic-induced dysbiosis with expansion of Trabulsiella (Proteobacteria), systemic propiogenic burden decreased. A phased dietary regimen emphasizing intact protein, combined with intermittent metronidazole therapy, favorably modulated biochemical and microbial parameters in MMA. These findings support microbiome-informed dietary strategies and selective gut-targeted interventions to optimize metabolic control in organic acidemias.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433242","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":"Advances in Therapeutics—Enzyme Replacement Therapy: Long-Term Evaluation and New Approaches","authors":"Robin Lachmann","doi":"10.1002/jimd.70166","DOIUrl":"10.1002/jimd.70166","url":null,"abstract":"<div>\u0000 \u0000 <p>The first enzyme replacement therapy (ERT) for a lysosomal storage disorder was marketed more than 30 years ago. We now have licensed products for 12 different conditions, and for a number of conditions, up to three different preparations are commercially available. These products were licensed on the basis of their ability to achieve pre-defined endpoints in clinical trials, but many have now been in clinical use for decades, and large amounts of real-world evidence have been generated. This has shown that not all treatments are equally effective and that there is still much unmet need, even for patients who have been treated for many years. Second-generation enzyme therapies are now being designed that will hopefully lead to improved clearance from currently hard-to-access cells and tissues, hence improving long-term clinical outcomes.</p>\u0000 </div>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432963","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":"Organoids for Metabolic Disease Modeling","authors":"Arif Ibrahim Ardisasmita,&nbsp;Edward Eelco Salomon Nieuwenhuis,&nbsp;Sabine Annemijn Fuchs","doi":"10.1002/jimd.70164","DOIUrl":"10.1002/jimd.70164","url":null,"abstract":"<p>Inherited metabolic diseases (IMDs) are a diverse group of rare genetic disorders that disrupt metabolic pathways, leading to severe clinical manifestations. Disease models ranging from complex animal models to simple in vitro systems have provided insights into IMDs, but each has limitations. Organoids, three-dimensional in vitro models, bridge this gap by replicating key metabolic functions that are absent in most simple 2D cell models. While organoids do not fully mimic organ complexity, they effectively model disease-specific metabolic defects, as seen in methylmalonic acidemia, Wilson's disease, and cystic fibrosis. Recognizing that function is more critical than organ resemblance, we propose focusing on the specific function of interest rather than selecting a model solely based on its derivation from the most affected organ. Focusing on specific biological processes enables precise, disease-relevant studies that drive novel therapeutic strategies and personalized medicine.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"49 2","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12974558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147433278","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}