Metabolism open最新文献

{"title":"Higher serum uric acid levels and risk of all-cause mortality in general population: a systematic review and meta-analysis","authors":"Md Golam Rabbani ,&nbsp;Sheikh M. Alif ,&nbsp;Cammie Tran ,&nbsp;Amanda J. Rickard ,&nbsp;Lisa Demos ,&nbsp;John J. McNeil ,&nbsp;Md Nazmul Karim","doi":"10.1016/j.metop.2025.100371","DOIUrl":"10.1016/j.metop.2025.100371","url":null,"abstract":"<div><h3>Background</h3><div>Population-based studies have reported a relationship between high serum uric acid (SUA) levels and all-cause mortality; however, findings are inconsistent. To address this issue, we conducted a meta-analysis of general population-based studies.</div></div><div><h3>Methods</h3><div>A systematic search was conducted in PubMed, Ovid Medline, EMBASE, and Web of science to identify relevant peer-reviewed articles using pre-specified search terms. Population-based cohort studies investigating the association between SUA levels and all-cause mortality were included. Risk ratios (RR) for all-cause mortality were calculated for higher and lower SUA levels based on data reporting on exposure and outcome. A meta-analysis based on a log-transformed random effect maximum likelihood model was used to obtain summary risk estimates. Heterogeneity was assessed through subgroup analysis and meta-regression of the study-level covariates.</div></div><div><h3>Results</h3><div>Thirty-four studies with more than 2.5 million participants were identified and analysed. Higher SUA levels were associated with an increased risk of all-cause mortality (RR: 1.32; 95 % confidence intervals (CIs):1.26–1.39, p &lt; 0.001). The risk of mortality was higher in women (RR:1.91; 95 %CI:1.40–2.61, p &lt; 0.001) compared to men (RR:1.16; 95 %CI:1.08 1.24, p &lt; 0.001). Subgroup analyses suggested that middle-aged adults (RR: 1.52, 95 %CI: 1.35–1.68), individuals living in OECD countries (RR:1.39, 95 %CI:1.28–1.49) and those of Caucasian ethnicity (RR:1.43, 95 %CI:1.35–1.51) reported a greater impact of elevated SUA levels on all-cause mortality.</div></div><div><h3>Conclusions</h3><div>Higher SUA levels were associated with a significant increase in the risk of all-cause mortality, with women appearing to be at greater risk than men. These findings highlight the need for research into mechanisms underlying the association between SUA and mortality and the reason for the sex difference identified.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100371"},"PeriodicalIF":0.0,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic regulation of Th17 and Treg cell balance by the mTOR signaling","authors":"Zhengzheng Wang ,&nbsp;Zhen Xu ,&nbsp;Ming Zong ,&nbsp;Lieying Fan","doi":"10.1016/j.metop.2025.100369","DOIUrl":"10.1016/j.metop.2025.100369","url":null,"abstract":"<div><div>The balance between T helper type 17 (Th17) and regulatory T (Treg) cells is crucial for maintaining immune homeostasis. The breakdown of this equilibrium is strongly associated with autoimmune disorders, though the regulatory mechanism of the Th17/Treg plasticity is less well demonstrated. The glycolytic metabolism plays a vital role in regulating the Th17/Treg cell differentiation. The review addressed the importance of mammalian target of rapamycin (mTOR) signaling in the glycolysis pathway attributed to Th17/Treg cell balance and consequence. Notably, we discuss the consequences of its equilibrium that lead to various autoimmune diseases, which might provide a new insight into the potentially therapeutic drug target for autoimmune disorders.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100369"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep quality and well-being in obesity-hypoventilation syndrome versus obstructive sleep apnea with obesity: A comparative study","authors":"Vasiliki Epameinondas Georgakopoulou ,&nbsp;Athina Lazaridou ,&nbsp;Athanasios Voulgaris ,&nbsp;Kostas Archontogeorgis ,&nbsp;Maria Dalamaga ,&nbsp;Evangelia Nena ,&nbsp;Paschalis Steiropoulos","doi":"10.1016/j.metop.2025.100367","DOIUrl":"10.1016/j.metop.2025.100367","url":null,"abstract":"<div><h3>Background</h3><div>Only a few studies in the published literature have assessed the well-being, and the sleep quality (SQ) in patients with obesity hypoventilation syndrome (OHS). The aim of this study was to evaluate well-being and SQ in patients with OHS and to compare these outcomes with those of patients with obstructive sleep apnea (OSA) and obesity.</div></div><div><h3>Methods</h3><div>Consecutive subjects being referred for evaluation of sleep disordered breathing were enrolled in the study. Patients were divided into two groups: Group A: OSA patients with BMI ≥30 kg/m² and 2) Group B: OHS patients. Well-being was assessed using the World Health Organization-Five Well-Being Index (WHO-5), while sleep quality was evaluated using the Pittsburgh Sleep Quality Index (PSQI).</div></div><div><h3>Results</h3><div>In total 1010 participants (OHS, n = 203) were included in the study. No difference was observed between groups in mean scores of Epworth Sleepiness Scale (ESS), Fatigue Severity Scale (FSS), WHO-5, and PSQI questionnaires. In patients with OHS, WHO-5 score was negatively correlated with neck circumference (r = −0.703, p = 0.016) and waist circumference (r = −0.728, p = 0.011). Moreover, PSQI scores in this group were significantly correlated with BMI (r = 0.410, p = 0.038). A lower WHO-5 score was observed in OHS patients with diabetes mellitus compared to non-diabetic patients with OHS (p = 0.049).</div></div><div><h3>Conclusions</h3><div>Patients with OSA and OHS reported similarly poor well-being and SQ. In patients with OHS, both high neck - and waist circumference were associated with poor well-being, while higher BMI was associated with worse sleep quality. Additionally, the well-being of OHS patients with concomitant diabetes mellitus was worse compared to OHS patients without diabetes mellitus.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100367"},"PeriodicalIF":0.0,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A direct effect of sulfatide against development of fibrosis","authors":"Rikke Thea ,&nbsp;Karsten Buschard","doi":"10.1016/j.metop.2025.100368","DOIUrl":"10.1016/j.metop.2025.100368","url":null,"abstract":"","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100368"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143904542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential role of adipokines and hepatokines in age-related ocular diseases","authors":"Stavroula Almpanidou,&nbsp;Ilias D. Vachliotis,&nbsp;Antonis Goulas,&nbsp;Stergios A. Polyzos","doi":"10.1016/j.metop.2025.100365","DOIUrl":"10.1016/j.metop.2025.100365","url":null,"abstract":"<div><div>Age-related ocular diseases, including diabetic retinopathy (DR), age-related macular degeneration (AMD), cataract and glaucoma may lead to visual impairment and even to blindness. Metabolic diseases, such as obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) have emerged as potential risk factors of age-related ocular diseases, especially DR. Visceral adiposity has been associated with increased risk of DR and AMD in most clinical studies, although body mass index has to-date provided conflicting association with DR and AMD. In addition, obesity is recognized as a risk factor of cataract and glaucoma. Similarly to obesity, MASLD appears to be associated with DR in patients with type 1 diabetes mellitus, but probably not in those with type 2 diabetes mellitus. A potential positive association between MASLD and AMD, glaucoma and cataract is supported by limited evidence to-date, thus needing further investigation. Altered secretion patterns of adipokines (adiponectin, leptin, lipocalin-2, resistin) and hepatokines [adropin, fetuin-A, fibroblast growth factor (FGF)-21, retinol binding protein (RBP)-4] seem to disrupt ocular homeostasis and contribute to the development of age-related ocular diseases in the context of obesity and MASLD. In this regard, novel adipokine-based and hepatokine-based therapies may be added to the treatment options for ocular diseases in the future. This narrative review aimed to summarize evidence on the interconnection of obesity and MASLD with age-related ocular diseases, with a specific focus on the roles of adipokines and hepatokines as mediators of these potential associations.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100365"},"PeriodicalIF":0.0,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143854373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive profiling of candidate biomarkers and immune infiltration landscape in metabolic dysfunction-associated steatohepatitis","authors":"Zhangliu Jin ,&nbsp;Jianyun Cao ,&nbsp;Zhaoxun Liu ,&nbsp;Mei Gao ,&nbsp;Hailan Liu","doi":"10.1016/j.metop.2025.100366","DOIUrl":"10.1016/j.metop.2025.100366","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing, with an incompletely understood pathophysiology involving multiple factors, particularly innate and adaptive immune responses. Given the limited pharmacological treatments available, identification of novel immune metabolic targets is urgently needed. In this study, we aimed to identify hub immune-related genes and potential biomarkers with diagnostic and predictive value for MASH patients.</div></div><div><h3>Methods</h3><div>The GSE164760 dataset from the Gene Expression Omnibus was utilized for analysis, and the R package was used to identify differentially expressed genes. Immune-related differentially expressed genes (IR-DEGs) were identified by comparing the overlap of differentially expressed genes with well-known immune-related genes. Furthermore, the biological processes and molecular functions of the IR-DEGs were analyzed. To characterize the hub IR-DEGs, we employed a protein-protein interaction network. The diagnostic and predictive values of these hub IR-DEGs in MASH were confirmed using GSE48452 and GSE63067 datasets. Finally, the significance of the hub IR-DEGs was validated using a mouse model of MASH.</div></div><div><h3>Results</h3><div>A total of 91 IR-DEGs were identified, with 61 upregulated and 30 downregulated genes. Based on the protein-protein interaction network, FN1, RHOA, FOS, PDGFRα, CCND1, PIK3R1, CSF1, and FGF3 were identified as the hub IR-DEGs. Moreover, we found that these hub genes are closely correlated with immune cells. Notably, the validation across two independent cohorts as well as a murine MASH model confirmed their high diagnostic potential.</div></div><div><h3>Conclusion</h3><div>The hub IR-DEGs, such as FN1, RHOA, FOS, PDGFRα, CCND1, PIK3R1, CSF1, and FGF3, may enhance the diagnosis and prognosis of MASH by modulating immune homeostasis.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100366"},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoglycemia compensation mechanisms in dry fasting","authors":"Ioannis-Eleemon Papagiannopoulos-Vatopaidinos ,&nbsp;Maria I. Papagiannopoulou ,&nbsp;Eleni N. Dotsika","doi":"10.1016/j.metop.2025.100363","DOIUrl":"10.1016/j.metop.2025.100363","url":null,"abstract":"<div><h3>Background</h3><div>Dry fasting (DF) presents three primary risks: hypovolemia, hypertonicity, and hypoglycemia. The first two have been shown to be effectively compensated, and the respective mechanisms have been studied. The behavior of glucose has only been roughly described, while the hypoglycemia compensation mechanisms remain unexplored.</div></div><div><h3>Objectives</h3><div>Studying the glucose behavior, the hypoglycemia compensation mechanisms, and the insulin resistance during DF.</div></div><div><h3>Methods</h3><div>Following parameters were daily monitored in ten participants undergoing a 5-day DF: Weight, body circumferences, glucose, creatinine clearance (GFR), insulin, HOMA-IR, acetoacetate in 24-h urine, glucagon, growth hormone (GH), IGF-1, TSH, T₄, T₃, leptin, cholesterol, LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides, and the enzymes LDH, CPK, SGPT, SGOT, and γGT.</div></div><div><h3>Results</h3><div>Weight, body circumferences, TSH, T₃, and T₄ decreased to minima on Day 5; insulin and HOMA-IR decreased, reaching minima on Day 4; GH, cholesterol, LDL-C, and acetoacetate increased to maxima on Day 5; Glucagon, IGF-1, and GFR increased, presenting maxima on Day 4; Glucose, leptin, and triglycerides exhibited biphasic profiles with minima on Days 3, 3, and 2, respectively; HDL-C, LDH, CPK, SGPT, SGOT, and γGT showed minimal or non-significant changes.</div></div><div><h3>Conclusion</h3><div>A comprehensive description of glucose behavior and the hypoglycemia compensation mechanisms in DF were presented. DF decreased insulin resistance, likely by improving the blood – cell interphase, and enhanced GFR. The increase in LDL-C, tissue-protecting IGF-1, and late increase in leptin and triglycerides were unexpected. The results may inform the development of novel therapeutic approaches for obesity, metabolic syndrome, type-2-diabetes, non-alcoholic fatty liver disease, adiposity, and atheromatous diseases.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100363"},"PeriodicalIF":0.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Truncated variant rs373056577 confers increased risk of type 2 diabetes and missense variant rs121912717 is associated with hypertriglyceridemia in Bangladeshi population","authors":"Shomoita Sayed ,&nbsp;Abdullah Al Saba ,&nbsp;Imrul Hasan ,&nbsp;Rafia Rahat ,&nbsp;Mohammad Sayem ,&nbsp;Akio Ebihara ,&nbsp;A.H.M. Nurun Nabi","doi":"10.1016/j.metop.2025.100364","DOIUrl":"10.1016/j.metop.2025.100364","url":null,"abstract":"<div><div>This study investigates the association of allelic and genotypic variations of rs121912717 and rs373056577 within APOA1 and APOA2 genes, respectively with the risk of type 2 diabetes (T2D). In this cross-sectional study, real-time quantitative PCR with specific Taqman probes was used to determine the genotypic and allelic frequencies of rs121912717 and rs373056577 in 300 unrelated Bangladeshi individuals (Healthy = 144, T2D patients = 156). Logistic regression analysis was performed to investigate the association of genotypic and allelic frequencies of these SNPs with respect to T2D under different inheritance models. Neither allelic nor genotypic frequencies of rs121912717 within APOA1 showed any significant association with T2D. Genotypes with respect to rs373056577 within APOA2 showed significant association with the risk of T2D under co-dominant heterozygous model (GG vs GA) [OR (95 %CI): 2.64 (1.32–5.59), p = 0.008], dominant [OR (95 %CI): 2.31 (1.24–4.49), p = 0.01] and over-dominant [OR (95 %CI): 2.62 (1.31–5.53), p = 0.008] models without adjusting for age, gender and BMI. After adjusting for age, gender and BMI, the A allele of rs373056577 showed significant association with T2D only in the dominant model [OR (95 %CI): 3.20 (1.12–10.51), p = 0.04]. Also, A allele of rs373056577 demonstrated significant association with the risk of T2D compared to allele G with [OR (95 %CI): 2.90 (1.15–8.14), p = 0.03] and without adjusting for confounders [OR (95 %CI): 1.97 (1.14–3.52), p = 0.02]. The genotypic frequency was significantly associated with T2D in codominant, dominant, and overdominant models in male participants when a gender-stratified analysis was conducted for rs373056577. However, when the logistic regression analysis was adjusted for age and BMI, the association was not significant in any of the models with respect to rs373056577 for male participants. On the other hand, gender-stratified regression analyses revealed no significant association with T2D before and after adjusting for age and BMI with respect to both allelic and genotypic frequencies of rs121912717. Individuals with CT genotype of rs121912717 had significantly higher triglyceride levels (322.2 mg/dL) compared to those harboring CC genotype (202.8 mg/dL) with or without adjusting for age, gender, BMI and disease status of the study participants. In conclusion, this study revealed that individuals harboring the allele A of rs373056577 possessed an increased risk of developing T2D and individuals having CT genotype of rs121912717 had increased triglyceride levels. The result of this study needs to be validated in a larger cohort for a more robust assessment.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100364"},"PeriodicalIF":0.0,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diabetic ketoacidosis treatment outcomes and associated factors among adult diabetic patients in Ethiopia: A systematic review and meta-analysis","authors":"Tsegaamlak Kumelachew Derse ,&nbsp;Desalegn Metiku Kidie ,&nbsp;Addisu Simachew Asgai ,&nbsp;Tadios lidetu ,&nbsp;Moges Tadesse Abebe","doi":"10.1016/j.metop.2025.100360","DOIUrl":"10.1016/j.metop.2025.100360","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic ketoacidosis is a severe complication of diabetes that can threaten life and has a considerable effect on healthcare systems, especially in developing nations such as Ethiopia. Although it is clinically significant, comprehensive data on the factors that lead to unsatisfactory treatment outcomes in diabetic ketoacidosis patients in Ethiopia are lacking. This review aims to investigate and evaluate unsatisfactory treatment outcomes and multiple contributing factors related to diabetic ketoacidosis among patients with diabetes in Ethiopia. This review seeks to identify these factors to provide insights that can guide improvements in the management and treatment of diabetic patients.</div></div><div><h3>Methods</h3><div>Articles documenting unfavorable treatment outcomes and related aspects of diabetic ketoacidosis among Ethiopian diabetes patients were meticulously sought from various databases, including PubMed/MEDLINE, the Cochrane Library, Science Direct, HINARI, Google Scholar, and gray literature. After the data were extracted, they were imported into Stata software version 17 for analysis. The Cochrane Q test and I² statistic were used to evaluate heterogeneity.</div></div><div><h3>Results</h3><div>A total of 580 duplicates were eliminated from the initial set of 1578 papers obtained from PubMed (3), Google Scholar (1,550), HINARI (11), Science Direct (13), and the Cochrane Library (1). The pooled prevalence of poor treatment outcomes for diabetic ketoacidosis was 8 %. Key risk factors for poor treatment outcomes included a Glasgow Coma Scale (GCS) score of less than 15 (POR = 3.16; 95 % CI: 1.52–4.80), sepsis (POR = 2.92; 95 % CI: 1.12–4.72), and comorbidities (POR = 3.66; 95 % CI: 1.64–5.68).</div></div><div><h3>Conclusion</h3><div>The pooled prevalence of poor treatment outcomes of diabetic ketoacidosis in Ethiopia was high. A GCS score of less than 15, sepsis, and comorbidities were identified as significant risk factors for poor treatment outcomes in diabetic ketoacidosis patients. Addressing and minimizing these factors could help reduce the incidence of poor treatment outcomes in diabetic ketoacidosis patients in Ethiopia.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100360"},"PeriodicalIF":0.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143734849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical diagnosis, treatment, and genetic analysis of adolescent onset holocarboxylase synthetase deficiency and cobalamin C deficiency: A case report and literature review","authors":"Ye Ren ,&nbsp;Hongxing Dang ,&nbsp;Yueqiang Fu ,&nbsp;Chengjun Liu ,&nbsp;Jing Li ,&nbsp;Jinhua Cai","doi":"10.1016/j.metop.2025.100361","DOIUrl":"10.1016/j.metop.2025.100361","url":null,"abstract":"<div><h3>Background</h3><div>Holocarboxylase Synthetase Deficiency (HCSD) is an uncommon autosomal recessive genetic disorder that manifests with symptoms such as metabolic acidosis, lethargy, hypotonia, seizures, and persistent rashes, typically emerging during infancy. The HLCS gene has been identified as the source of pathogenic mutations associated with this condition. Cobalamin C (cblC) deficiency is another rare autosomal recessive disorder resulting from defects in cobalamin metabolism, attributable to mutations in the MMACHC gene. This disorder often leads to methylmalonic aciduria and homocystinuria and is classified into early-onset and late-onset types. The late-onset type is characterized by acute or chronic progressive neurological symptoms and behavioral disturbances. To date, there have been no documented cases worldwide of individuals diagnosed with both HCSD and cobalamin C deficiency.</div></div><div><h3>Case presentation</h3><div>This report details the case of an 11-year-and-9-month-old female patient from China who presented with symptoms including vomiting, altered consciousness, and a rash. Laboratory evaluations indicated the presence of metabolic acidosis, methylmalonic aciduria, and homocystinuria. Genetic analysis revealed mutations in the MMACHC gene: c.482G &gt; A (p.R161Q) and c.567dup (p.I190Yfs∗13). Additionally, two previously unreported mutations in the HLCS gene, c.1922G &gt; T (p.G641V) and c.1754C &gt; T (p.P585L), were identified. She was diagnosed with Holocarboxylase Synthetase Deficiency and Cobalamin C deficiency. The child showed significant improvement following treatment with hydroxocobalamin, betaine, and biotin.</div></div><div><h3>Conclusion</h3><div>This article reports a case of adolescent onset HCSD and cobalamin C deficiency. Treatment with hydroxocobalamin, betaine, and biotin is effective. Two novel mutations in the HLCS gene causative for HCSD have been reported, providing a broader foundation for mutational screening and offering insights into the diagnosis and treatment of similar disorders.</div></div>","PeriodicalId":94141,"journal":{"name":"Metabolism open","volume":"26 ","pages":"Article 100361"},"PeriodicalIF":0.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143704719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}