Molecular Genetics and Metabolism Reports最新文献

{"title":"First reported case of adult-onset very long-chain acyl-coa dehydrogenase (vlcad) deficiency in Vietnam: a rare metabolic myopathy","authors":"Vinh Phuc Kieu ,&nbsp;Thang Van Viet Nguyen ,&nbsp;Anh Duc Vu","doi":"10.1016/j.ymgmr.2025.101286","DOIUrl":"10.1016/j.ymgmr.2025.101286","url":null,"abstract":"<div><div>Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a rare genetic metabolic disorder involving impaired fatty acid β-oxidation. It is caused by mutations in the Acyl-CoA Dehydrogenase Very Long Chain (ACADVL) gene, which encodes the VLCAD enzyme. The clinical presentation is diverse, ranging from a severe neonatal-onset form to a milder adult-onset form. We describe the first reported case in Vietnam, which is a 20-year-old man who presented with exercise intolerance, myalgia, and recurrent rhabdomyolysis triggered by fasting and exertion. Acylcarnitine profiling suggested a fatty acid oxidation disorder, and whole-exome sequencing identified the diagnosis of VLCAD deficiency with c747G &gt; T (p.Trp249Cys) mutation. It has not previously been reported in the Vietnamese population. This case highlights the important role of neonatal screening and genetic testing in the early diagnosis of metabolic myopathies. In addition, it raises awareness of genetic disorders among healthcare providers and the public in developing countries.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101286"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidental maternal glutaric aciduria type I detection through newborn screening: A case report","authors":"Pierre-Edouard Grillet ,&nbsp;Cecilia Marelli ,&nbsp;Etienne Mondésert ,&nbsp;Marie-Céline Francois-Heude ,&nbsp;Agathe Roubertie ,&nbsp;Frédérique Sabourdy ,&nbsp;Jean-Paul Cristol ,&nbsp;Cécile Acquaviva ,&nbsp;Stéphanie Badiou","doi":"10.1016/j.ymgmr.2026.101300","DOIUrl":"10.1016/j.ymgmr.2026.101300","url":null,"abstract":"<div><div>The expansion of newborn screening in France (2023–2025) to include carnitine metabolism disorders has increased false positives, often due to unsuspected maternal metabolic conditions. We report the first french incidental diagnosis of a glutaric acidemia type I in a mother following a low C0 carnitine level detected on her newborn's screening. Genetic analysis revealed a previously undescribed mutation in the <em>GCDH</em> gene at a homozygote state consistent with an asymptomatic but high-excretor biochemical profile.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101300"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of glutamate metabolism in Niemann-pick disease type C1 mice","authors":"Antony Cougnoux,&nbsp;Carolina S. Alvarez,&nbsp;Andrea Gutierrez Maria,&nbsp;Emelin Hernandez,&nbsp;Niamh X. Cawley,&nbsp;Cristin D. Davidson,&nbsp;Forbes D. Porter","doi":"10.1016/j.ymgmr.2026.101303","DOIUrl":"10.1016/j.ymgmr.2026.101303","url":null,"abstract":"<div><div>Niemann-Pick disease, type C1 (NPC1) is a lysosomal disease that results in progressive loss of Purkinje neurons. Previous work has implicated dysregulation of glutamate signaling as a potential pathogenic mechanism. In this study, we explore the efficacy of AMPA receptor inhibition and the role of SLC1A6, a Purkinje neuron glutamate transporter, in NPC1 cerebellar pathology.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101303"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147397685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Congenital disorder of deglycosylation 2. Report of a novel MAN2C1 pathogenic variant and additional phenotypic implications","authors":"Rafael Luis Aguirre-Guillen ,&nbsp;Luis Ángel Arredondo-Navarro ,&nbsp;María Fernanda Hernández-Rodríguez ,&nbsp;Martín-De La Torre Eduardo ,&nbsp;Contreras Peregrina María del Rosario ,&nbsp;Mayra Alejandra Arce-Lozoya ,&nbsp;Estefanía Ochoa-Padilla ,&nbsp;Víctor Ulises Rodríguez-Machuca","doi":"10.1016/j.ymgmr.2026.101289","DOIUrl":"10.1016/j.ymgmr.2026.101289","url":null,"abstract":"<div><div>The <em>MAN2C1</em> gene encodes an enzyme with alpha-mannosidase 2C1 activity, which is responsible for the degradation of defective glycoproteins in the cytoplasm. The purpose of this report is to present a novel <em>MAN2C1</em> pathogenic variant in a patient with a congenital disorder of deglycosylation 2. We describe a case with 15q24.1q24.3 microdeletion syndrome which also presented a deleterious variant in the <em>MAN2C1</em> gene located at the opposite allele. We discussed the phenotypic consequences when <em>MAN2C1</em> gene transcript is missing.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101289"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galactose tolerance in adults with classical galactosaemia. Considering the gaps","authors":"L.A. Shakerdi ,&nbsp;C. Newman Thacker ,&nbsp;K. Moore ,&nbsp;A. Sheerin ,&nbsp;M. Noga ,&nbsp;M.E. Rubio-Gozalbo ,&nbsp;G.T. Berry ,&nbsp;J.J. O'Byrne ,&nbsp;R. Saldova ,&nbsp;E.P. Treacy","doi":"10.1016/j.ymgmr.2026.101298","DOIUrl":"10.1016/j.ymgmr.2026.101298","url":null,"abstract":"<div><div>Classical galactosaemia (CG, OMIM <span><span>230400</span><svg><path></path></svg></span>) is a rare inborn error of metabolism caused by deficiency of galactose-1-phosphate uridylyltransferase. The available modality of treatment, a galactose-restricted diet, is effective in preventing life-threatening neonatal symptoms. However long-term complications including neurological, speech and fertility issues in females remain prevalent.</div></div><div><h3>Methods</h3><div>This retrospective review reports the experience of mild-moderate relaxation of dietary galactose intake over time in a cohort of 31 Irish CG adult patients with established RBC Gal-1-P, and novel IgG <em>N</em>-glycan analysis. Three groups were categorised based on the retrospective analysis of estimated dietary galactose intake: Group 1 (&lt;200 mg/day), Group 2 (200–500 mg/day) and Group 3 (501-1000 mg/day). Dietary galactose intake was compared to matching RBC Gal-1-P levels and serum IgG <em>N-</em>glycan profiles (measured by HILIC-UPLC).</div></div><div><h3>Results</h3><div>RBC Gal-1-P levels increased with increased galactose intake with statistically significant differences only between the lowest and highest galactose intake group (<em>p</em> &lt; 0.05). Minor changes were seen in a number of IgG <em>N</em>-glycans in the highest galactose intake group with increases in core fucosylated monoantennary and biantennary monogalactosylated monosialylated glycans, pentamannosylated glycans, oligomannosylated glycans and monoantennary glycans with a decrease in grouped biantennary glycans. The most significant change noted was an increase in pentamannosylated glycans with increased dietary galactose intake.</div></div><div><h3>Conclusion</h3><div>Moderate relaxation of dietary galactose intake (up to 500 mg/day) may be well tolerated in the majority of CG adults. These data suggest that serum <em>N</em>-glycan profiling may provide an improved individualised ‘personalised medicine’ approach for treatment interventions for CG, considering individualised variation in glycosylation, including ‘glycosylation outliers’.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101298"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a UQCRC1 variant in a patient with progressive weakness, pain and sleep issues reveals a functional mitochondrial defect restored by mitochondrial transplantation","authors":"Gerardo G. Piroli ,&nbsp;Rebecca Myers ,&nbsp;Lynda Holloway ,&nbsp;Andrew Hayek ,&nbsp;Ellen Linebaugh ,&nbsp;Julie R. Jones ,&nbsp;Cindy Skinner ,&nbsp;Steven A. Skinner ,&nbsp;Norma Frizzell ,&nbsp;Richard Steet","doi":"10.1016/j.ymgmr.2026.101302","DOIUrl":"10.1016/j.ymgmr.2026.101302","url":null,"abstract":"<div><div>Primary mitochondrial defects underlie the heterogeneity of many rare inherited disorders. Pathogenic variants that disrupt the function of the multi-subunit protein complexes of the mitochondrial respiratory chain contribute to a range of neurological phenotypes and other clinical manifestations. These variants are also thought to contribute to the onset and progression of numerous more common neurodegenerative conditions such as Parkinson's and Alzheimer's disease. Here we describe an individual affected with progressive muscle weakness and pain harboring a paternally inherited missense variant in <em>UQCRC1</em>, encoding a subunit of Complex III. Biochemical characterization of cells from the proband and his father demonstrated normal steady-state levels of UQCRC1 and UQCRC2 protein. Functional assessment of mitochondrial respiration in lymphoblasts and fibroblasts, however, showed a clear deficit in respiratory parameters in the proband, with a more attenuated response in the father. Lastly, we demonstrate that healthy mitochondria isolated from HEK293 cells can be transferred to the patient lymphoblasts, restoring basal mitochondrial respiration and ATP production. Perspectives on the contribution of this variant to the patient phenotypes, and the potential of mitochondrial transplantation and different compounds as treatment modalities for patients with primary mitochondrial deficits, is discussed.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101302"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147355745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Branched-chain amino acid transferase 2 (BCAT2) deficiency: A case series and systematic review","authors":"Maja Filipic ,&nbsp;Ziga Iztok Remec ,&nbsp;Ana Drole Torkar ,&nbsp;Nataša Sustar ,&nbsp;Vanja Cuk ,&nbsp;Chiara Rodaro ,&nbsp;Maruša Debeljak ,&nbsp;Matej Mlinaric ,&nbsp;Jaka Sikonja ,&nbsp;Vesna Bancic Silva ,&nbsp;Primoz Kotnik ,&nbsp;Tadej Battelino ,&nbsp;Mojca Zerjav Tansek ,&nbsp;Urh Groselj ,&nbsp;Barbka Repic Lampret","doi":"10.1016/j.ymgmr.2026.101291","DOIUrl":"10.1016/j.ymgmr.2026.101291","url":null,"abstract":"<div><h3>Background</h3><div>Branched-chain amino acid transaminase 2 (BCAT2) deficiency is an autosomal recessive disorder that impairs branched-chain amino acid (BCAA) catabolism. Its clinical and metabolic features remain poorly understood due to limited reports in the literature.</div></div><div><h3>Methods</h3><div>We report three novel cases of BCAT2 deficiency from Slovenia: one diagnosed following symptom onset, one through cascade screening of parents, and one by newborn screening. Diagnosis was established through metabolic evaluation and confirmation of pathogenic variants in the <em>BCAT2</em> gene. In addition, we performed a systematic review of all previously reported cases of BCAT2 deficiency.</div></div><div><h3>Results</h3><div>All three patients were homozygous for the NM_001190.4:c.600C &gt; A (p.Tyr200Ter) variant, with valine concentrations at presentation of 2093, 2589, and 794 μmol/L. Only one patient was symptomatic, presenting with headaches, developmental delay, and intellectual disability, while the remaining two were largely asymptomatic. Notably, insulin resistance was observed in one of the three patients and may be associated with elevated BCAA levels. Systematic literature review identified 8 additional cases of BCAT2 deficiency. Genetic variant c.600C &gt; A was also found in two Pakistani individuals, while the remaining variants were each reported in only a single individual. The most common clinical characteristics were intellectual disability (55%), developmental delay and other neurological symptoms (36%). Abnormal white matter findings on MRI were observed in all patients who underwent imaging. BCAA levels decreased in all patients receiving pyridoxine supplementation; however, only 50% showed clinical improvement.</div></div><div><h3>Conclusion</h3><div>BCAT2 deficiency displays marked interindividual heterogeneity, ranging from asymptomatic cases to severe neurological impairment, which renders its pathogenicity uncertain.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"46 ","pages":"Article 101291"},"PeriodicalIF":1.9,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146024223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on: Lee J.Z.C. et al. Case report: Hepatocellular carcinoma in a patient with Pyridoxamine 5-phosphate oxidase (PNPO) deficiency undergoing pyridoxal 5-phosphate (PLP) treatment. Mol Genet Metab Rep. 2025;9;43:101224.","authors":"P. De Liso ,&nbsp;R. Webster ,&nbsp;B. Plecko ,&nbsp;F. Vigevano","doi":"10.1016/j.ymgmr.2025.101248","DOIUrl":"10.1016/j.ymgmr.2025.101248","url":null,"abstract":"","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101248"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144896732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carbonic anhydrase VA deficiency due to a novel CA5A variant","authors":"Laura Keehan ,&nbsp;Elizabeth Null ,&nbsp;Lekha Chilakamarri ,&nbsp;Christopher Carter ,&nbsp;Chung Lee ,&nbsp;Gregory M. Enns ,&nbsp;Dena R. Matalon","doi":"10.1016/j.ymgmr.2025.101259","DOIUrl":"10.1016/j.ymgmr.2025.101259","url":null,"abstract":"<div><div>Carbonic anhydrase VA (CA-VA) deficiency is a rare autosomal recessive inborn error of metabolism characterized by variable neonatal onset metabolic acidosis, hyperammonemia, lactic acidosis, and ketonuria. To date, there have been 41 cases of CA-VA deficiency described in the literature. Here, we report the clinical history and biochemical laboratory findings of a newborn female with a novel homozygous missense variant in <em>CA5A</em>. This case adds to the literature of biochemical findings and ancestral diversity in individuals with CA-VA deficiency.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101259"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145219998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular characterization of a novel synonymous variant in a Mexican patient with Pompe disease","authors":"Carmen Alaez-Verson ,&nbsp;Carlos Alberto González-Domínguez ,&nbsp;Imelda Vergara Sanchez ,&nbsp;Luz María Sanchez Sanchez ,&nbsp;Ivonne Natalia Flores ,&nbsp;Ekaterina Kazakova ,&nbsp;Joaquin Garcia-Solorio ,&nbsp;Carolina Molina-Garay ,&nbsp;Luis Leonardo Flores-Lagunes ,&nbsp;Ivan Martínez Duncker","doi":"10.1016/j.ymgmr.2025.101253","DOIUrl":"10.1016/j.ymgmr.2025.101253","url":null,"abstract":"<div><h3>Introduction</h3><div>Pompe disease (PD) is an autosomal recessive disorder caused by a deficiency of lysosomal acid alpha-1,4-glucosidase (GAA; EC 3.2.1.20), encoded by the GAA gene, leading to progressive neuromuscular deterioration. The mutational spectrum of <em>GAA</em> is expanding, particularly with recognition of splicing-impacting synonymous variants. Here, we report the molecular characterization and reclassification of a novel synonymous <em>GAA</em> variant in a female Mexican patient with enzymatically confirmed infantile-onset PD (IOPD).</div></div><div><h3>Methods</h3><div>DNA and RNA were extracted from peripheral blood. Next-generation sequencing of a clinical exome panel identified variants in the <em>GAA</em> gene. The whole coding sequence of the <em>GAA</em> was amplified from cDNA, subcloned, and analyzed by Sanger sequencing to assess splicing alterations.</div></div><div><h3>Results</h3><div>The pathogenic variant c.1979G &gt; A (p.Arg660His) and a novel VUS c.2799G &gt; A (p.Lys933=) were detected. The variant c.2799G &gt; A is predicted to affect splicing. mRNA analysis revealed three isoforms, one corresponding to c.1979G &gt; A and two others caused by alternative splicing of c.2799G &gt; A (isoforms 1 and 2). The isoform-1 showed c.2799G &gt; A, followed by 61 bp retention of intron 19, predicted to cause a frameshift p.(A934fs). Isoform 2 has a 90 bp deletion in exon 19, resulting in a p.V904_K933del in-frame deletion.</div></div><div><h3>Discussion</h3><div>This study demonstrates that the synonymous variant c.2799G &gt; A is pathogenic due to its impact on RNA splicing. Our findings highlight the importance of transcript analysis for VUS reclassification and stress the clinical relevance of evaluating synonymous variants in genetic diagnostics and patient management.</div></div>","PeriodicalId":18814,"journal":{"name":"Molecular Genetics and Metabolism Reports","volume":"45 ","pages":"Article 101253"},"PeriodicalIF":1.9,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145155271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}