Journal of Inherited Metabolic Disease最新文献

{"title":"The clinical utility in hospital-wide use of growth differentiation factor 15 as a biomarker for mitochondrial DNA-related disorders","authors":"Andrea Cortés Fernández,&nbsp;Jane Estrella,&nbsp;Devin Oglesbee,&nbsp;Austin A. Larson,&nbsp;Johan L.K. Van Hove","doi":"10.1002/jimd.12821","DOIUrl":"10.1002/jimd.12821","url":null,"abstract":"<p>Clinical recognition of primary mitochondrial disorders (PMD) is difficult due to the clinical and genetic heterogeneity. Whereas lactate has low sensitivity and specificity, in structured clinical studies growth differentiation factor 15 (GDF15) has shown promise with elevations in mitochondrial DNA (mtDNA)-related PMD, but its specificity has been questioned. In a tertiary care hospital-wide study, medical records were retrospectively reviewed from 418 cases where GDF15 levels were obtained by clinicians. Patients were classified into patients with PMD due to mtDNA-related defects (mtDNA maintenance, mtDNA deletions, and mtDNA-encoded tRNA variants), PMD due to structural defects or other nuclear causes, and in non-mitochondrial disease. Patients with liver disease or systemic critical illness were excluded. GDF15 was assayed in a clinical laboratory with a cutoff of 750 ng/L. There were 38 mtDNA-related PMD (GDF15 &gt;750 pg/mL in 76%), 35 other nuclear DNA-encoded PMD or structural subunits (31% elevated GDF15), 309 non-mitochondrial disorders (13% elevated GDF15). Based on the highest Youden J-index, the optimal cut-off value to identify these target mtDNA-related disorders was 815 pg/mL, with sensitivity 76%, specificity 88%, positive predictive value of 41% and negative predictive value of 97%. At this optimized cutoff level, mtDNA-encoded PMD patients had elevated GDF15 in 76%, nuclear DNA-encoded PMD in 26%, and non-mitochondrial disorders in 11% of patients. Thus, in a real-life clinical setting, after excluding abnormal liver function and critical illness, GDF15 had good clinical utility increasing the odds at predicting mtDNA-related primary mitochondrial disorders 14-fold, but not for structural or other nuclear-encoded primary mitochondrial disorders.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710396","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":"Epidemiology and economic burden of Wilson disease in France: A nationwide population-based study","authors":"Shona Fang,&nbsp;Martina Furegato,&nbsp;Jessica Azzi,&nbsp;Eduardo Couchonnal-Bedoya,&nbsp;Dominique Debray","doi":"10.1002/jimd.12822","DOIUrl":"10.1002/jimd.12822","url":null,"abstract":"<p>Wilson disease (WD) is a rare inherited copper metabolism disorder characterized by progressive pathological deposition of copper, primarily in the liver and brain. This longitudinal retrospective study conducted using the French national claims (Système National des Données de Santé [SNDS]) database assessed WD prevalence in France, described patients' characterizations and healthcare resource use and associated costs. Patients with WD were identified from SNDS using the International Classification of Diseases, 10th Revision code E83.0 for copper metabolism disorder or a long-term disease (affection de longue durée [ALD]) associated with this code between 2010 and 2019. Patients were categorized into hepatic, neurological, and psychiatric sub-cohorts. We identified 2287 patients with WD yielding a crude prevalence of 1 case per 33 898 individuals in 2019. The mean age at inclusion was 39.9 (standard deviation [SD] 22.8) years, 11 years more than that of the incident cohort (28.6, SD 20.3) identified via ALD, and 1180 (51.6%) patients were male. The crude mortality was 3.2% (in total 370 patients died). Overall, 1011 (44.2%), 754 (33.0%), and 414 (18.1%) patients experienced hepatic, neurological, and psychiatric manifestations, respectively. In total, 922 (40.3%) patients were reimbursed for WD-specific treatment, the most common being D-penicillamine (74.8%), and 201 (8.8%) underwent liver transplantation. The average annual hospitalization cost per patient was 4273.7€ (SD 11916.0). At least one sick leave was reported for 533 (23.3%) patients, with an annual average cost of 788.7€ (SD 1328.6). Our findings provide an updated understanding of the prevalence of WD, and indicate a considerable level of morbidity in this population, as well as a high level of direct/indirect costs associated with WD.</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/PMC11670285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710277","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":"My path to citrin deficiency","authors":"John E. Walker","doi":"10.1002/jimd.12818","DOIUrl":"10.1002/jimd.12818","url":null,"abstract":"<p>Citrin belongs to the SLC25 transport protein family found mostly in inner mitochondrial membranes. The family prototype, the ADP–ATP carrier, delivers ATP made inside mitochondria to the cellular cytoplasm and returns ADP to the mitochondrion for resynthesis of ATP. In pre-genomic 1981, I noticed that the protein sequence of the bovine ADP–ATP carrier consists of three related sequences, each containing two transmembrane α-helices traveling in opposite senses. Colleagues and I demonstrated that two other mitochondrial carriers had similar features. From emergent genomic sequences, it became apparent that they represented a large family of transport proteins with the same characteristic threefold repeats. The human genome encodes 53 members, but the functions of many were unknown. So, colleagues and I determined how to make these proteins in <i>Escherichia coli</i> and introduce them into liposomes to allow exploration of their transport functions. The 27 human family members to have been thus identified include citrin and the closely related protein aralar. Both exchange aspartate from the mitochondrial matrix for cytosolic glutamate plus a proton. Citrin is expressed predominantly in liver and non-excitable tissues, whereas aralar is the dominant form in the brain. Each has a membrane extrinsic N-terminal Ca²⁺-binding domain, a transport domain, and a C-terminal amphipathic α-helix. Human mutations in citrin impair the urea cycle, malate–aspartate shuttle, gluconeogenesis, amino acid breakdown, and energy metabolism leading to citrin deficiency. Currently, the complex etiology of this condition is poorly understood and new knowledge would help to improve diagnosis, therapies, and finding a cure. My aims are to seek a basic understanding of the etiology of citrin deficiency and to use that knowledge in improving diagnostic procedures and in developing new treatments and a cure.</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/PMC11670154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142710393","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":"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}

{"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}

{"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}

{"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}

{"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}

{"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}

{"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}