Journal of Inherited Metabolic Disease最新文献

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Potential therapeutic uses of L-citrulline beyond genetic urea cycle disorders 除遗传性尿素循环障碍外,L-瓜氨酸的潜在治疗用途
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-24 DOI: 10.1002/jimd.12810
Marshall Summar
{"title":"Potential therapeutic uses of L-citrulline beyond genetic urea cycle disorders","authors":"Marshall Summar","doi":"10.1002/jimd.12810","DOIUrl":"https://doi.org/10.1002/jimd.12810","url":null,"abstract":"<p>L-citrulline (referred to hereafter as citrulline), a non-essential amino acid and an intermediate in the urea cycle, is widely recognized for its role in managing genetic urea cycle disorders (UCDs). Recent studies, however, suggest that citrulline's therapeutic potential extends beyond UCDs, particularly in conditions associated with nitric oxide (NO) deficiency, endothelial dysfunction, and oxidative stress. This review explores citrulline's emerging applications in sickle cell disease (SCD), post-operative pulmonary hypertension (PH), hepatic veno-occlusive disease (HVOD), and bronchopulmonary dysplasia (BPD), as well as its speculative use in asthma and acute respiratory distress syndrome (ARDS). In SCD, citrulline may restore NO bioavailability, potentially reducing the incidence and severity of vaso-occlusive crises and preventing complications like pulmonary hypertension. In the context of post-operative PH, citrulline's capacity to enhance NO production can improve pulmonary vascular resistance, decrease right ventricular strain, and reduce the need for mechanical ventilation. Citrulline's protective effects on endothelial function and its ability to mitigate oxidative stress offer promising adjunctive therapy for HVOD, particularly in patients undergoing bone marrow transplantation. In BPD, citrulline could promote alveolar development, reduce inflammation, and improve long-term respiratory outcomes. Despite these promising findings, further research is necessary to determine optimal dosing strategies and to evaluate long-term efficacy and safety. The potential role of citrulline in modulating NO production in conditions like asthma and ARDS also warrants further investigation. This review underscores the versatile therapeutic potential of citrulline and highlights the need for continued research into its applications across various conditions associated with NO deficiency and endothelial dysfunction.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"47 6","pages":"1260-1268"},"PeriodicalIF":4.2,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142707988","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}
引用次数: 0
Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria 人类乙醛酸代谢再探:多器官参与的新发现,对基于 siRNA 的原发性高草酸尿症疗法的影响。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-24 DOI: 10.1002/jimd.12817
Ronald J. A. Wanders, Jaap W. Groothoff, Lisa J. Deesker, Eduardo Salido, Sander F. Garrelfs
{"title":"Human glyoxylate metabolism revisited: New insights pointing to multi-organ involvement with implications for siRNA-based therapies in primary hyperoxaluria","authors":"Ronald J. A. Wanders,&nbsp;Jaap W. Groothoff,&nbsp;Lisa J. Deesker,&nbsp;Eduardo Salido,&nbsp;Sander F. Garrelfs","doi":"10.1002/jimd.12817","DOIUrl":"10.1002/jimd.12817","url":null,"abstract":"<p>Glyoxylate is a toxic metabolite because of its rapid conversion into oxalate, as catalyzed by the ubiquitous enzyme lactate dehydrogenase. This requires the presence of efficient glyoxylate detoxification systems in multiple subcellular compartments, as glyoxylate is produced in peroxisomes, mitochondria, and the cytosol. Alanine glyoxylate aminotransferase (AGT) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR) are the key enzymes involved in glyoxylate detoxification. Bi-allelic mutations in the genes coding for these enzymes cause primary hyperoxaluria type 1 (PH1) and 2 (PH2), respectively. Glyoxylate is derived from various sources, including 4-hydroxyproline, which is degraded in mitochondria, generating pyruvate and glyoxylate, as catalyzed by the mitochondrial enzyme 4-hydroxy-2-oxoglutarate aldolase (HOGA); however, counterintuitively, a defect in <i>HOGA1</i> is the molecular basis of primary hyperoxaluria type 3 (PH3). Irrespective of its underlying cause, hyperoxaluria in humans leads to nephrocalcinosis, recurrent urolithiasis, and kidney damage, which may culminate in kidney failure requiring combined liver-kidney transplantation in severely affected patients. In the past few years, therapeutic options, especially for primary hyperoxaluria type 1 (PH1), have greatly been improved thanks to the introduction of two RNAi-based therapies that inhibit either the production of glycolate oxidase (lumasiran) or lactate dehydrogenase (nedosiran). While lumasiran only targets PH1 patients, nedosiran was specifically developed to target all three subtypes of PH. Inspired by the findings reported in the literature that nedosiran effectively reduced urinary oxalate excretion in PH1 patients but not in PH2 or PH3 patients, we have now revisited glyoxylate metabolism in humans and performed a thorough literature study which revealed that glyoxylate/oxalate metabolism is not confined to the liver but instead involves multiple different organs. This new view on glyoxylate/oxalate metabolism in humans may well explain the disappointing results of nedosiran in PH2 and PH3, and provides new clues for the future generation of new therapeutic strategies for PH2 and PH3.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710379","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}
引用次数: 0
Development of a novel tool for individual treatment trials in mucopolysaccharidosis 开发用于粘多糖病个体治疗试验的新型工具。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-21 DOI: 10.1002/jimd.12816
Anna-Maria Wiesinger, Brian Bigger, Roberto Giugliani, Christina Lampe, Maurizio Scarpa, Tobias Moser, Christoph Kampmann, Georg Zimmermann, Florian B. Lagler
{"title":"Development of a novel tool for individual treatment trials in mucopolysaccharidosis","authors":"Anna-Maria Wiesinger,&nbsp;Brian Bigger,&nbsp;Roberto Giugliani,&nbsp;Christina Lampe,&nbsp;Maurizio Scarpa,&nbsp;Tobias Moser,&nbsp;Christoph Kampmann,&nbsp;Georg Zimmermann,&nbsp;Florian B. Lagler","doi":"10.1002/jimd.12816","DOIUrl":"10.1002/jimd.12816","url":null,"abstract":"<p>Mucopolysaccharidosis (MPS) encompasses a group of genetic lysosomal storage disorders, linked to reduced life expectancy and a significant lack of effective treatment options. Immunomodulatory drugs could have the potential to be a relevant medical approach, as the accumulation of undegraded substances initiates an innate immune response, which leads to inflammation and clinical deterioration. However, immunomodulators are not licensed for this indication. Consequently, we aim to provide evidence advocating fast access to innovative individual treatment trials (ITTs) with immunomodulatory drugs and high-quality evaluation of drug effects by implementing a risk–benefit model tailored for MPS. The iterative methodology of our novel decision analysis framework (DAF) involves three key steps: (i) literature review on promising treatment targets and immunomodulators in MPS; (ii) quantitative risk–benefit assessment (RBA) of selected molecules; (iii) assigning phenotypic profiles and quantitative evaluations. The results facilitate a personalized application of the model and are based on published evidence as well as interdisciplinary experts' consensus and patient perspectives. Four promising immunomodulators have been identified: adalimumab, abatacept, anakinra, and cladribine. An improvement in mobility is most likely with adalimumab, while anakinra is anticipated as a treatment of choice for neuronopathic MPS patients. Nevertheless, a comprehensive RBA should always be completed on an individual basis. Our evidence-based DAF tool for ITTs directly addresses the substantial unmet medical need in MPS and characterizes an initial stride toward precision medicine with immunomodulators.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670214/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687087","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}
引用次数: 0
Endocannabinoid receptor 2 is a potential biomarker and therapeutic target for the lysosomal storage disorders 内源性大麻素受体2是溶酶体贮积症的潜在生物标志物和治疗靶点。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-21 DOI: 10.1002/jimd.12813
Calogera M. Simonaro, Makiko Yasuda, Edward H. Schuchman
{"title":"Endocannabinoid receptor 2 is a potential biomarker and therapeutic target for the lysosomal storage disorders","authors":"Calogera M. Simonaro,&nbsp;Makiko Yasuda,&nbsp;Edward H. Schuchman","doi":"10.1002/jimd.12813","DOIUrl":"10.1002/jimd.12813","url":null,"abstract":"<p>Herein, we studied the expression of endocannabinoid receptor 2 (CB2R), a known inflammation mediator, in several lysosomal storage disorder (LSD) animal models and evaluated it as a potential biomarker and therapeutic target for these diseases. CB2R was highly elevated in the plasma of Farber disease and mucopolysaccharidosis (MPS) type IIIA mice, followed by Fabry disease and MPS type I mice. Mice with acid sphingomyelinase-deficient Niemann-Pick disease (ASMD) and rats with MPS type VI exhibited little or no plasma CB2R elevation. High-level expression of CB2R was also observed in tissues of Farber and MPS IIIA mice. Treatment of MPS IIIIA patient cells with CB2R agonists led to a reduction of CB2R and monocyte chemoattractant protein-1 (MCP-1), a chemotactic factor that is elevated in this LSD. Treatment of MPS IIIA mice with one of these agonists (JWH133) led to a reduction of plasma and tissue CB2R and MCP-1, a reduction of glial fibrillary acidic protein (GFAP) in the brain, and an improvement in hanging test performance. JWH133 treatment of Farber disease mice also led to a reduction of MCP-1 in tissues and plasma, and treatment of these mice by enzyme replacement therapy (ERT) led to a reduction of plasma CB2R, indicating its potential to monitor treatment response. Overall, these findings suggest that CB2R should be further examined as a potential therapeutic target for the LSDs and may also be a useful biomarker to monitor the impact of therapies.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681978","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}
引用次数: 0
Brain morphometry in hepatic Wilson disease patients 肝性威尔逊病患者的大脑形态测量。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-19 DOI: 10.1002/jimd.12814
Parya Rahimi, Stanislav Mareček, Radan Brůha, Monika Dezortová, Petr Sojka, Milan Hájek, Marta Skowrońska, Łukasz Smoliński, Petr Urbánek, Tomasz Litwin, Petr Dušek
{"title":"Brain morphometry in hepatic Wilson disease patients","authors":"Parya Rahimi,&nbsp;Stanislav Mareček,&nbsp;Radan Brůha,&nbsp;Monika Dezortová,&nbsp;Petr Sojka,&nbsp;Milan Hájek,&nbsp;Marta Skowrońska,&nbsp;Łukasz Smoliński,&nbsp;Petr Urbánek,&nbsp;Tomasz Litwin,&nbsp;Petr Dušek","doi":"10.1002/jimd.12814","DOIUrl":"10.1002/jimd.12814","url":null,"abstract":"<p>Wilson disease (WD) primarily presents with hepatic and neurological symptoms. While hepatic symptoms typically precede the neurological manifestations, copper accumulates in the brain already in this patient group and leads to subclinical brain MRI abnormalities including T2 hyperintensities and atrophy. This study aimed to assess brain morphological changes in mild hepatic WD. WD patients without a history of neurologic symptoms and decompensated cirrhosis and control participants underwent brain MRI at 3T scanner including high-resolution T1-weighted images. A volumetric evaluation was conducted on the following brain regions: nucleus accumbens, caudate, pallidum, putamen, thalamus, amygdala, hippocampus, midbrain, pons, cerebellar gray matter, white matter (WM), and superior peduncle, using Freesurfer v7 software. Whole-brain analyses using voxel- and surface-based morphometry were performed using SPM12. Statistical comparisons utilized a general linear model adjusted for total intracranial volume, age, and sex. Twenty-six WD patients with mild hepatic form (30 ± 9 years [mean age ± SD]); 11 women; mean treatment duration 13 ± 12 (range 0–42) years and 28 healthy controls (33 ± 9 years; 15 women) were evaluated. Volumetric analysis revealed a significantly smaller pons volume and a trend for smaller midbrain and cerebellar WM in WD patients compared to controls. Whole-brain analysis revealed regions of reduced volume in the pons, cerebellar, and lobar WM in the WD group. No significant differences in gray matter density or cortical thickness were found. Myelin or WM in general seems vulnerable to low-level copper toxicity, with WM volume loss showing promise as a marker for assessing brain involvement in early WD stages.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142675918","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}
引用次数: 0
A Dutch translational knowledge agenda for inherited metabolic diseases 荷兰遗传代谢疾病转化知识议程。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-16 DOI: 10.1002/jimd.12812
Hans R. Waterham, Ronald J. A. Wanders, Ron A. Wevers, Clara D. van Karnebeek
{"title":"A Dutch translational knowledge agenda for inherited metabolic diseases","authors":"Hans R. Waterham,&nbsp;Ronald J. A. Wanders,&nbsp;Ron A. Wevers,&nbsp;Clara D. van Karnebeek","doi":"10.1002/jimd.12812","DOIUrl":"10.1002/jimd.12812","url":null,"abstract":"&lt;p&gt;The advancement of innovative diagnostics, such as newborn screening and -omics strategies targeting DNA, RNA and metabolites, has led to the identification of a rapidly growing number of patients with an inherited metabolic disorder (IMD) as well as new IMDs, currently encompassing more than 1500 distinct diseases (www.icimd.org). Concurrently, significant therapeutic milestones have been achieved and are being developed for a number of IMDs, including the creation of specific diets, enzyme replacement therapy and DNA/RNA targeting therapies. A recent review of ICIMD identified 287 IMDs amenable to one or more of these treatments (www.iembase.org).&lt;/p&gt;&lt;p&gt;Despite these advancements, or perhaps partly because of them, numerous clinical, scientific and societal challenges continue to impede the delivery of optimal care to the majority of IMD patients. To identify current knowledge gaps and areas for improvement (i.e. research questions), and to set priorities for the IMD field for the next 4–8 years with an emphasis on achieving improved care and outcomes for IMD patients, the “United for Metabolic Diseases” (UMD) consortium (www.umd.nl) in the Netherlands initiated the development of a Translational Knowledge Agenda for Inherited Metabolic Diseases. The process and outcomes, detailed in a publication in JIMD Reports&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; involved equal participation of professionals with diverse expertise as well as patient representatives. A multidisciplinary steering committee, comprising 12 metabolic experts—including laboratory specialists, metabolic researchers, metabolic pediatricians, internists, pediatric neurologists, dieticians, nurse specialists, and patient organizations- collected research questions from the field via an online survey using the snowball sampling method. A total of 158 participants completed the survey, with a balanced composition of 54% patient representatives and 46% healthcare professionals and researchers. The 462 proposed research questions were subsequently discussed, categorized and prioritized during a meeting attended by 22 representatives of the aforementioned stakeholder groups, using as main criteria: patient-centeredness, implications for the development of the entire field, unmet needs, feasibility of research and relevance for other stakeholders. The resulting top 10 research questions cover multiple themes, including prediction of disease progression, development of novel tools, mechanistic insights, improved diagnostics, therapeutic integration of multi-omics techniques, assessment of impact on daily life, expansion of treatment avenues, optimal study designs, effects of lifestyle interventions and data utilization following FAIR principles.&lt;/p&gt;&lt;p&gt;An essential aspect in the development of the knowledge agenda was the consistent incorporation of patients' input and perspectives at each development stage. This active patient engagement ensured the inclusion of lifestyle-related questions and psycho","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12812","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644354","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}
引用次数: 0
Current global vitamin and cofactor prescribing practices for primary mitochondrial diseases: Results of a European reference network survey 目前全球针对原发性线粒体疾病的维生素和辅助因子处方做法:欧洲参考网络调查结果。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-11-11 DOI: 10.1002/jimd.12805
Julia Neugebauer, Karit Reinson, Marcello Bellusci, Julien H. Park, Omar Hikmat, Enrico Bertini, Manuel Schiff, MetabERN PM-MD Consortium authors, Shamima Rahman
{"title":"Current global vitamin and cofactor prescribing practices for primary mitochondrial diseases: Results of a European reference network survey","authors":"Julia Neugebauer,&nbsp;Karit Reinson,&nbsp;Marcello Bellusci,&nbsp;Julien H. Park,&nbsp;Omar Hikmat,&nbsp;Enrico Bertini,&nbsp;Manuel Schiff,&nbsp;MetabERN PM-MD Consortium authors,&nbsp;Shamima Rahman","doi":"10.1002/jimd.12805","DOIUrl":"10.1002/jimd.12805","url":null,"abstract":"<p>Primary mitochondrial diseases (PMD) account for a group of approximately 400 different genetic disorders with diverse clinical presentations and pathomechanisms. Although each individual disorder is rare, collectively they represent one of the largest groups in the field of inherited metabolic disorders. The complexity of PMD results in a continued lack of therapeutic options, necessitating a predominantly symptomatic treatment approach for affected patients. While a subset of diseases responds exceptionally well to treatment with specific vitamins or cofactors, for most PMD systematic reviews were not able to show significant benefit. This is in discrepancy to their continued frequent use among specialists. To gain further insight into the current clinical practice of vitamin and cofactor supplementation among clinicians treating children and adults affected by PMD, we conducted a worldwide cross-sectional questionnaire study exploring the choice of substances and the specific diseases where they are applied. To our knowledge, this is the first global study exploring this topic and featuring a high response rate from paediatricians. The vast majority (95%, 106/112) of responding specialists recommended the use of vitamins and cofactors, either in an agnostic approach irrespective of the specific PMD or directed to the treatment of specific diseases or phenotypes. Our study highlights significant regional and specialty-specific differences in supplementation practices. We provide some preliminary insights into specialist-based opinions regarding the use of vitamins and cofactors in PMD and highlight the need for more rigorous clinical and preclinical investigations and/or clear consensus statements.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622235","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}
引用次数: 0
News from Valencia: JIMD themed issue on ureagenesis defects and allied disorders 来自巴伦西亚的新闻:关于尿原生成缺陷和相关疾病的 JIMD 主题刊物。
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-10-29 DOI: 10.1002/jimd.12811
Vicente Rubio, Johannes Häberle
{"title":"News from Valencia: JIMD themed issue on ureagenesis defects and allied disorders","authors":"Vicente Rubio,&nbsp;Johannes Häberle","doi":"10.1002/jimd.12811","DOIUrl":"10.1002/jimd.12811","url":null,"abstract":"&lt;p&gt;Valencia (Spain) was the birthplace of the urea cycle (UC) pioneer Santiago Grisolia. After 30 years in the United States, he returned in 1978 to live and work in Valencia, passing away just 3 months before the celebration there (16–20 October 2022) of the second “International Conference on Ureagenesis Defects (UCDs) and Allied Conditions 2022. Novel models and treatment options.” The first was held in Pontresina (Switzerland) in March 2018.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; The present JIMD themed issue contains presentations from the 70+ participants in the Valencia Conference (Appendix A). We dedicate this Editorial and entire JIMD issue to the memory of Dr. Grisolia.&lt;/p&gt;&lt;p&gt;The viewpoint review paper of Häberle, Siri and Dionisi-Vici&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; reflects the concept of UCDs “allied conditions” due to derangements of components ancillary to the UC. This materialized in our Conference on presentations on carbonic anhydrase 5A (CA5A) deficiency (poor bicarbonate supply to carbamoyl phosphate synthetase 1, CPS1), pyrroline-5-carboxylate synthetase deficiency (poor supply of de novo made ornithine), ornithine aminotransferase deficiency (potential cause of neonatal or early infantile hyperammonemia) and lysinuric protein intolerance (amino acid transport defect; it can also cause hyperammonemia). To take advantage of molecular analogies for propelling advances, the meeting also considered presentations on CAD and aralar deficiencies (MIM Nos. 612949 and 616457, respectively). CAD catalyzes the initial three steps of pyrimidine biosynthesis, encompassing paralogs of CPS1 and ornithine transcarbamylase (CPS2 and aspartate transcarbamylase). Aralar is the extrahepatic nearly-twin brother of citrin (UC transporter).&lt;/p&gt;&lt;p&gt;These “Allied Disorders” presentations have translated into two papers linked to this issue, one in JIMD Reports, led by Fathiya Al-Murshedi, highlighting the clinical variability for an 18-member cohort of patients of CA5A deficiency sharing the same mutation and living in the Arabic peninsula&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;; and the other paper (which appeared in JIMD volume 6, 2023),&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; from Santiago Ramón-Maiques's laboratory, which furthers the understanding of CAD and its deficiency and uses a fast experimental pathogenicity-testing cellular assay for CAD variants (including variants from Saskia Wortmann and Paula Sánchez-Pintos presentations).&lt;/p&gt;&lt;p&gt;Another novelty for a meeting held in a Western country was the devoting of an afternoon/evening to citrin deficiency. The time was ripe for this, as shown in Johannes Häberle solo paper in this issue.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt; The Citrin Foundation was our partner, funding this Spotlight session and being scientifically very well represented, with its Scientific Supervisory Board's Chairman, the Nobel Laureate (Chemistry, 1997) Sir John Walker, attending the meeting and delivering the keynote lecture that will translate into a paper on citrin deficiency (which","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"47 6","pages":"1117-1119"},"PeriodicalIF":4.2,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jimd.12811","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142545939","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}
引用次数: 0
The relation between dietary polysaccharide intake and urinary excretion of tetraglucoside 膳食多糖摄入量与尿液中四葡糖苷排泄量之间的关系
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-10-26 DOI: 10.1002/jimd.12801
Candelas Gross-Valle, Tessa C. Jacobs, Janneke D. A. Dijck-Brouwer, Janniek Lubberts, Barbara M. Bakker, Stephan J. L. Bakker, Yvonne van der Veen, Andrea B. Schreuder, Terry G. J. Derks, Jennifer van der Krogt, Joost Groen, M. Rebecca Heiner-Fokkema
{"title":"The relation between dietary polysaccharide intake and urinary excretion of tetraglucoside","authors":"Candelas Gross-Valle,&nbsp;Tessa C. Jacobs,&nbsp;Janneke D. A. Dijck-Brouwer,&nbsp;Janniek Lubberts,&nbsp;Barbara M. Bakker,&nbsp;Stephan J. L. Bakker,&nbsp;Yvonne van der Veen,&nbsp;Andrea B. Schreuder,&nbsp;Terry G. J. Derks,&nbsp;Jennifer van der Krogt,&nbsp;Joost Groen,&nbsp;M. Rebecca Heiner-Fokkema","doi":"10.1002/jimd.12801","DOIUrl":"10.1002/jimd.12801","url":null,"abstract":"<p>The urinary metabolite tetraglucoside (Glc4) is a potential biomarker for hepatic glycogen storage diseases (GSDs). Glc4 is believed to reflect body glycogen content and/or turnover. However, dietary polysaccharide intake may influence Glc4 excretion, potentially limiting the utility of Glc4 as a monitoring biomarker in hepatic GSDs. We aimed to investigate the association of dietary polysaccharide intake with Glc4 excretion. Urinary Glc4 excretion (mmol/mmol creatinine and mmol/24 h) was analyzed using a validated LC–MS/MS method. Data was analyzed from 65 kidney transplant recipients and 58 healthy kidney donors in the TransplantLines cohort study. Spearman's correlation and multivariable linear regression analyses were performed. In the multivariable analysis, dry lean body mass (DLBM), dietary polysaccharide intake, transplantation status, age, sex, and glycated hemoglobin (HbA1c) served as independent variables. Daily variation was examined in 21 healthy individuals of urinary Glc4 excretion in 2-h collections over a 24-h period. Mixed generalized additive models were built to study the association of prior polysaccharide intake with Glc4 excretion. No (univariate) associations were found between polysaccharide intake and Glc4 excretion. However, a significant interaction between DLBM and polysaccharide on 24 h Glc4 excretion was observed in the multivariate analysis. Glc4 excretion throughout the day exhibited no relationship to prior polysaccharide intake. Our findings suggest an indirect effect of polysaccharide intake on Glc4 excretion, potentially due to changes in muscle glycogen content and/or turnover. We have found no evidence that dietary polysaccharides under normal intakes increase urinary Glc4 directly.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502177","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}
引用次数: 0
Nontargeted urine metabolomic analysis of acute intermittent porphyria reveals novel interactions between bile acids and heme metabolism: New promising biomarkers for the long-term management of patients 急性间歇性卟啉症的非靶向尿液代谢组学分析揭示了胆汁酸与血红素代谢之间的新型相互作用:有望用于患者长期管理的新生物标记物
IF 4.2 2区 医学
Journal of Inherited Metabolic Disease Pub Date : 2024-10-25 DOI: 10.1002/jimd.12809
Thibaud Lefebvre, Thibaut Eguether, Etienne Thévenot, Antoine Poli, Emeline Chu-Van, Pranvera Krasniqi, Caroline Schmitt, Neila Talbi, Gaël Nicolas, Hervé Puy, Christophe Junot, Antonin Lamazière, Florence Castelli, Laurent Gouya, François Fenaille
{"title":"Nontargeted urine metabolomic analysis of acute intermittent porphyria reveals novel interactions between bile acids and heme metabolism: New promising biomarkers for the long-term management of patients","authors":"Thibaud Lefebvre,&nbsp;Thibaut Eguether,&nbsp;Etienne Thévenot,&nbsp;Antoine Poli,&nbsp;Emeline Chu-Van,&nbsp;Pranvera Krasniqi,&nbsp;Caroline Schmitt,&nbsp;Neila Talbi,&nbsp;Gaël Nicolas,&nbsp;Hervé Puy,&nbsp;Christophe Junot,&nbsp;Antonin Lamazière,&nbsp;Florence Castelli,&nbsp;Laurent Gouya,&nbsp;François Fenaille","doi":"10.1002/jimd.12809","DOIUrl":"10.1002/jimd.12809","url":null,"abstract":"<p>Acute intermittent porphyria is an inherited error of heme synthesis. The underlying pathophysiology, involving mainly hepatic heme synthesis, is poorly understood despite its occurrence, and the severity of acute porphyria attack is still difficult to control. A better understanding of the interactions between heme synthesis and global metabolism would improve the management of AIP patients. An untargeted metabolomic analysis was performed on the urine of 114 patients with overt AIP and asymptomatic carriers using liquid chromatography coupled to high-resolution mass spectrometry. The collected data were analyzed by combining univariate and multivariate analyses. A total of 239 metabolites were annotated in urine samples by matching chromatographic and mass spectral characteristics with those from our chemical library. Twenty-six metabolites, including porphyrin precursors, intermediates of tryptophan or glycine metabolism and, unexpectedly, bile acids, showed significant concentration differences between the phenotypic groups. Dysregulation of bile acid metabolism was confirmed by targeted quantitative analysis, which revealed an imbalance in favor of hydrophobic bile acids associated with changes in conjugation, which was more pronounced in the severe phenotype. Using a random forest model, the cholic acid/chenodeoxycholic acid ratio enables the differential classification of severe patients from other patients with a diagnostic accuracy of 84%. The analysis of urine samples revealed significant modifications in the metabolome of AIP patients. Alteration in bile acids provides new insights into the pathophysiology of chronic complications, such as primary liver cancer, while also providing new biomarker candidates for predicting the most severe phenotypes.</p>","PeriodicalId":16281,"journal":{"name":"Journal of Inherited Metabolic Disease","volume":"48 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142502147","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}
引用次数: 0
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