JIMD reports最新文献

{"title":"Identification of Additional Cases of Severe Neonatal GABA-Transaminase Deficiency","authors":"Deima Alammary,&nbsp;Tisiana Low,&nbsp;Ganesh Srinivasan,&nbsp;Marie-Claude Dery,&nbsp;Mahmoud Almutadares,&nbsp;Samantha Marin,&nbsp;Mubeen F. Rafay,&nbsp;Katya Rozovsky,&nbsp;Patrick Frosk","doi":"10.1002/jmd2.70069","DOIUrl":"10.1002/jmd2.70069","url":null,"abstract":"<p>GABA-transaminase (GABA-T) deficiency is a rare disorder of GABA metabolism characterized by neonatal encephalopathy, epilepsy, hypotonia and intellectual disability. It is caused by biallelic pathogenic variants in the <i>ABAT</i> gene. We report a case of a newborn female born to a G10P5 mother, with abnormal fetal movements and polyhydramnios in utero. At birth, she presented with hypotonia, hypersomnolence, decreased level of consciousness, central hypoventilation, non-epileptic myoclonus, seizures, and neurogenic diabetes insipidus. Brain MRI on day two of life showed partial cerebellar vermis agenesis and cerebellar hemispheric dysplasia. Her EEG demonstrated burst suppression. Family history was significant for two siblings with a similar neonatal course. On rapid whole exome sequencing she was found to be homozygous for a nonsense variant in the <i>ABAT</i> gene designated c.1278C&gt;A, p.Tyr426*. Both of her affected siblings were also found to be homozygous for the same variant, and carrier status was confirmed in both parents. A trial of flumazenil infusion showed subtle EEG improvement. Our report of three siblings with severe GABA-T deficiency provides evidence for founder effect in the Canadian Indigenous population and discusses the utility of urine GABA quantification as a reasonable screening test.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12820413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146029558","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":"Hypoaminoacidemia and Pyroglutamic Aciduria: Potential Biomarkers in Malnutrition-Related Hyperammonemia","authors":"M. M. Crenshaw,&nbsp;O. M. D'Annibale,&nbsp;V. Martucci,&nbsp;S. Gracie,&nbsp;A. Kochhar,&nbsp;J. Stansauk,&nbsp;A. Larson,&nbsp;P. Baker II,&nbsp;C. Peck,&nbsp;T. Wood,&nbsp;A. El-Gharbawy,&nbsp;S. McCandless,&nbsp;M. K. LoPiccolo","doi":"10.1002/jmd2.70058","DOIUrl":"https://doi.org/10.1002/jmd2.70058","url":null,"abstract":"<p>Hyperammonemia is a medical emergency, and the cause must be identified quickly in order to treat appropriately. Malnutrition is a known risk factor for hyperammonemia; however, there are limited reliable lab indicators used to identify malnutrition. Early identification of the etiology of hyperammonemia is crucial to optimizing care, specifically reintroduction of appropriate amounts of protein into the diet. Herein, we discuss three patients with complex medical histories and clinical signs of malnutrition who presented with hyperammonemia. In all three patients, both hypoaminoacidemia and pyroglutamic aciduria were observed. Specifically, all patients had low tyrosine, tryptophan, methionine, and branched-chain amino acids. Recognizing this biochemical pattern could result in more rapid initiation of supplementing protein, a primary tenet of treatment in malnutrition-related hyperammonemia. We highlight the unique features of malnutrition-related hyperammonemia, propose mechanisms to explain the pattern, and suggest a framework for managing these cases.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146007811","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":"Biochemical, Clinical, and Functional Characterization of a Rare c.-106C>A Promoter Region Variant in Late-Onset Ornithine Transcarbamylase Deficiency: A Multifamily Case Series","authors":"Samuel Quinn Tholl,&nbsp;Wendy McCaul,&nbsp;Anthony Rupar,&nbsp;Melanie P. Napier,&nbsp;Natalya Karp,&nbsp;Andrea C. Yu,&nbsp;Suzanne Ratko,&nbsp;Aneal Khan,&nbsp;Michael Geraghty,&nbsp;Chitra Prasad","doi":"10.1002/jmd2.70064","DOIUrl":"10.1002/jmd2.70064","url":null,"abstract":"<p>Ornithine transcarbamylase (OTC) deficiency can present during the neonatal period, infancy, or adulthood. Late-onset phenotypes are influenced by residual enzyme activity and <i>OTC</i> gene expression. The objective of this study was to assess the pathogenicity of a rare promoter region variant, c.-106C&gt;A. We reviewed three independent pedigrees harboring the c.-106C&gt;A variant. Retrospective chart reviews were conducted for 16 affected males to evaluate biochemical and clinical features. Functional OTC enzyme data were obtained from the liver biopsy of three affected males. The median age of diagnosis for symptomatic males was 15 years (range: 0.08–55). All 21 heterozygous females have been asymptomatic to date. Of the 16 hemizygous males, seven have experienced at least one episode of hyperammonemia, and eight have remained asymptomatic. The proband from Family A presented at age 55, with a peak ammonia level of 694 μmol/L. His OTC activity was 8.2 μmol/g liver/min (control: 94.9 μmol/g liver/min). The proband from Family B presented at age 15 with an ammonia level of 1568 μmol/L and later died from cerebral edema. His OTC activity was 2.2 μmol/g liver/min (control: 73.2 μmol/g liver/min). The proband from Family C presented at age 24 with hyperammonemia and later died following withdrawal of care. His liver punch biopsy OTC enzyme activity was measured to be 0 μmol/g liver/min (control range: 25–31.7 μmol/g liver/min). For most affected males, ammonia scavenger therapy has successfully prevented recurrent decompensation. The combined biochemical, clinical, and enzymatic data strongly support the pathogenicity of the c.-106C&gt;A <i>OTC</i> promoter region variant in late-onset OTC deficiency.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12808918/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145998126","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":"Liver Transplantation in PNPO Deficiency: Management Challenges and Biological Lessons","authors":"Richard Webster,&nbsp;Bindu Parayil Sankaran,&nbsp;Sushil Bandodkar,&nbsp;Michael Stormon,&nbsp;Gordon Thomas,&nbsp;Albert Shun,&nbsp;David Geoffrey Bowen,&nbsp;Timothy Fielder,&nbsp;Peter Barclay,&nbsp;Youssef Khalil,&nbsp;Philippa Mills,&nbsp;Peter Clayton,&nbsp;Kaustuv Bhattacharya","doi":"10.1002/jmd2.70067","DOIUrl":"https://doi.org/10.1002/jmd2.70067","url":null,"abstract":"<p>Pyridox(am)ine 5′ Phosphate Oxidase deficiency (PNPO) presents with refractory epilepsy responsive to treatment with pyridoxal 5′ phosphate (PLP) or pyridoxine. A 15-year-old boy with PNPO deficiency and cirrhosis underwent orthotopic liver transplantation for hepatocellular carcinoma without extra-hepatic disease. Pre-transplant, the boy was cognitively normal with well controlled epilepsy on PLP 50 mg/kg/day. Continuous EEG monitoring was used pre-operatively and post-operatively to identify encephalopathy resulting from PLP deficiency. B6 vitamers (pyridoxine [PN], pyridoxamine [PM], pyridoxal [PL] and phosphorylated forms [PNP, PMP, PLP]) were assayed at times of encephalopathy (symptoms and/or EEG) and for pharmacokinetics. Doses of PLP were titrated to prevent encephalopathy and limit side effects. The intraoperative/immediate postoperative periods were managed with intravenous PLP at a dose which could be reduced to 7.8 mg/kg/day before encephalopathy recurred. Post-transplant, transition to oral PLP (100 mg/kg/day) led to fulminant hepatic impairment, which improved when IV dosing resumed. Subsequent transition to full oral PLP dosing took 9 months with a final dose of 24 mg/kg/day oral PLP. PLP showed dose dependent hepatotoxicity with associated rises in alpha-fetoprotein levels. Gradual PLP dose changes and frequent oral dosing minimised encephalopathy episodes and hepato-toxicity. Six years post-transplant, liver biopsy showed moderate portal fibrosis (Ishak fibrosis stage 2/6, LAFSc score 3/9). Encephalopathy/seizures were associated with lower plasma PL concentrations (40 times above physiological levels); but high plasma PLP concentrations did not prevent encephalopathy. Despite liver transplantation, requirements for supraphysiologic doses of PLP continued, suggesting impaired neuronal PLP salvage is the major factor determining PLP requirements in PNPO deficiency.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958159","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":"Treatable Neonatal Molybdenum Cofactor Deficiency: Rapid Demise Despite Rapid Biochemical Diagnosis","authors":"Molly M. Crenshaw,&nbsp;Yasmeen Midgette,&nbsp;Shruthi Mohan,&nbsp;Ruhan Wei,&nbsp;Mariele Anneling,&nbsp;Monika Williams,&nbsp;Milap Patel,&nbsp;Benjamin T. Cocanougher,&nbsp;Sarah P. Young,&nbsp;Dmitriy Niyazov,&nbsp;Areeg El-Gharbawy,&nbsp;Ashlee R. Stiles","doi":"10.1002/jmd2.70061","DOIUrl":"https://doi.org/10.1002/jmd2.70061","url":null,"abstract":"<p>Molybdenum cofactor deficiency (MoCD) is an inborn error of metabolism included in the differential for refractory neonatal seizures. The prognosis is guarded, with a median reported age of death between 2.4 and 3.0 years. Mortality is primarily due to seizures and lower respiratory tract infections. MoCD has a distinct biochemical profile, characterized by elevated urinary <i>S</i>-sulfocysteine, xanthine, and hypoxanthine, and low or undetectable serum and urine uric acid levels. A disease-altering treatment is available for MoCD Type A; however, due to the rarity of the condition, its natural history remains poorly understood. We present a patient with neonatal-onset refractory seizures, whose biochemical testing, performed within 24 h of specimen receipt in the laboratory, revealed a pattern consistent with MoCD. Before the genetics team could disclose the preliminary diagnosis, the patient demised, without evidence of worsening seizures or respiratory infection. Results of genome sequencing, guided by biochemical findings, identified double homozygous pathogenic variants in <i>MOCS1</i> (associated with MoCD Type A). Although the biochemical genetics laboratory's protocol for analyzing and reporting <i>S</i>-sulfocysteine levels within 48 h enabled a rapid preliminary diagnosis, the patient's condition deteriorated too quickly to initiate disease-altering treatment, progressing more rapidly than described in the literature. We discuss potential hypotheses for his rapid decline and the broader implications for the field of biochemical genetics.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jmd2.70061","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145964063","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":"Therapeutic Monitoring of Patients With Hereditary Tyrosinemia Type 1—A Belgian Monocentric Experience","authors":"Anne-Sophie Adam,&nbsp;Lionel Marcélis,&nbsp;David Fage,&nbsp;Elise Mathieu,&nbsp;Aurélie Empain,&nbsp;Céline Dufour,&nbsp;Frédéric Cotton,&nbsp;Corinne de Laet","doi":"10.1002/jmd2.70062","DOIUrl":"10.1002/jmd2.70062","url":null,"abstract":"<p>Hereditary tyrosinemia type I (HT-1) is a rare metabolic disorder treated by NTBC, requiring careful therapeutic and nutritional monitoring. While follow-up traditionally relies on urinary succinylacetone, plasma NTBC and plasma amino acids, dried blood spot (DBS) methods have introduced alternative monitoring options. However, the optimal biochemical monitoring remains debated. This study evaluated the clinical utility of NTBC measurements compared with established biomarkers in HT-1. In this retrospective single-centre study, we analysed biological data from 12 HT-1 patients treated with NTBC over 6 years. We analysed correlations between NTBC, succinylacetone, δ-aminolevulinic acid (δ-ALA) and alpha-fetoprotein concentrations, and compared tyrosine and phenylalanine levels in DBS and plasma. Succinylacetone suppression in both urine and blood was achieved across a broad range of NTBC concentrations, suggesting that blood succinylacetone is a more reliable marker of metabolic control than NTBC levels. Elevated urinary δ-ALA levels were observed in some samples despite unquantifiable succinylacetone, indicating that succinylacetone may not fully reflect neurological risk. NTBC concentrations showed limited correlation with alpha-fetoprotein, reinforcing the continued need for imaging in hepatocellular carcinoma surveillance. DBS measurement of tyrosine and phenylalanine displayed variable biases relative to plasma, particularly for tyrosine, highlighting the challenges of using DBS for nutritional monitoring. While NTBC remains central in the treatment of HT-1 patients, its blood concentrations offer limited added value for long-term monitoring. Focusing on succinylacetone measurement, along with δ-ALA and alpha-fetoprotein to evaluate neurological and hepatic risks, is recommended. Plasma remains the preferred matrix for amino acids monitoring. Larger multi-centre studies are needed to confirm these findings.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12779275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933364","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":"Efzimfotase Alfa Improves Respiratory Capacity in Muscle Tissue From a Mouse Model of HPP","authors":"Denise Devore,&nbsp;Juan Ruanova,&nbsp;Walter Voegtli,&nbsp;Derek Dunn,&nbsp;John Decker,&nbsp;Maurizio Mazzantini,&nbsp;Vincenzo De Tata,&nbsp;Maria Concetta Scavuzzo,&nbsp;Francesco Conti,&nbsp;Anna Petryk,&nbsp;Maria Luisa Brandi","doi":"10.1002/jmd2.70057","DOIUrl":"10.1002/jmd2.70057","url":null,"abstract":"<p>Hypophosphatasia (HPP) is an inherited metabolic disease caused by deficient tissue-nonspecific alkaline phosphatase (ALP) activity and characterized by skeletal and nonskeletal symptoms, including muscle weakness and fatigue. We hypothesized that mitochondrial respiration is impaired in muscle in HPP, independent of skeletal manifestations, and that the second-generation ALP enzyme replacement therapy (ERT) efzimfotase alfa improves respiration. Akp2GW^−/− mice were used for this purpose. Body weight, bone mineralization, and survival were validated in Akp2GW^−/− mice versus Akp2^−/− mice, an established model of HPP. No significant differences were found, validating the Akp2GW^−/− model. Respiratory outcomes were measured in skeletal muscle fiber bundles in age- and sex-matched Akp2GW^−/− and Akp2GW^+/+ (wild-type) mice; bone mineralization was assessed. Mean maximal respiration and mitochondrial spare respiratory capacity (SRC) in vehicle-treated Akp2GW^−/− mice were 37% and 30% of values from wild-type mice, respectively, independent of skeletal manifestations. Efzimfotase alfa treatment significantly improved maximal respiration in tissue from Akp2GW^−/− mice by 147% versus vehicle (<i>p</i> = 0.0059) and improved SRC by 262% versus vehicle (<i>p</i> = 0.0008). Mean maximal respiration and SRC in tissue from efzimfotase alfa-treated Akp2GW^−/− mice were 92% and 107%, respectively, of tissue from wild-type mice. Cellular ultrastructure of muscle biopsies from people with HPP showed atypical mitochondrial morphology, including branching cristae and dispersed matrix. In a mouse model of HPP, we show that the altered mitochondrial respiration in skeletal muscle is improved by ERT and that HPP is characterized by altered muscle mitochondrial morphology in humans. Together, these data suggest ERT could improve muscular symptoms in HPP.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12755057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889143","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":"A Multisystem Perspective of Pediatric Cell Trafficking Disorders: Within the Cells, Beneath the Signs","authors":"Merve Yoldaş Çelik,&nbsp;Burcu Köşeci,&nbsp;Ezgi Burgaç,&nbsp;Kanay Yararbaş,&nbsp;Tamer Çelik,&nbsp;Esra Sarıgeçili,&nbsp;Habibe Koç Uçar","doi":"10.1002/jmd2.70053","DOIUrl":"10.1002/jmd2.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <p>Cell trafficking disorders(CTDs) are rare, heterogeneous inherited conditions marked by impaired intracellular transport mechanisms such as vesicular trafficking, cytoskeletal dynamics, and organelle interactions. Although clinical awareness is increasing, CTDs are often underdiagnosed due to phenotypic overlap with mitochondrial, lysosomal, and glycosylation disorders. We retrospectively analyzed 14 pediatric patients with molecularly confirmed CTDs at a single center. Clinical, biochemical, imaging, and genetic findings were reviewed to explore genotype–phenotype relationships and shared clinical features. The cohort included 8 females and 6 males, with a median diagnostic age of 29 months (range: 1–86 months). Common initial symptoms were developmental delay, hypotonia, seizures, and hepatosplenomegaly. MRI abnormalities were noted in 7 patients. Elevated serum lactate and dicarboxylic aciduria were observed in 9 and 6 patients, respectively. Creatine kinase was raised in several cases, prominently in one with TANGO2 deficiency. Elevated AST (<i>n</i> = 12) and ALT (<i>n</i> = 5) indicated mild hepatic involvement. Immunological abnormalities included immunoglobulin deficiency (<i>n</i> = 3) and protein C/S deficiency (<i>n</i> = 4). Recurrently mutated genes were <i>AP4M1</i> and <i>NPC1</i> (<i>n</i> = 2 each); others included <i>BSCL2</i>, <i>PACS1</i>, <i>RAB3GAP1</i>, <i>STXBP1</i>, <i>TANGO2</i>, <i>HERC1</i>, <i>KIF1A</i>, <i>ATP1A3</i>, <i>VPS13B</i>, and <i>NLGN3</i>. Two novel variants were identified: AP4M1 c.929 + 1G&gt;T and NPC1 c.145A&gt;T. This case series highlights the clinical and biochemical convergence of genetically diverse CTDs, emphasizing the role of trafficking defects in neurodevelopmental and systemic dysfunction. Expanding diagnostic panels to include trafficking-related genes and adopting a mechanism-based classification may improve early recognition and tailored management of these complex disorders.</p>\u0000 </section>\u0000 </div>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12744936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145856351","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":"Reversing Acute Cardiomyopathy With Coenzyme Q10 Supplementation in Cobalamin B Disease: A Case Report and Literature Review","authors":"Dalia Said,&nbsp;Aisha Al Shamsi","doi":"10.1002/jmd2.70063","DOIUrl":"10.1002/jmd2.70063","url":null,"abstract":"<p>Methylmalonic acidemia (MMA) is a rare metabolic disorder with various subtypes, including Cobalamin B (cblB) disease. While cardiac complications are well-documented in propionic acidemia, their occurrence in MMA is less understood. Here, we report a 12-year-old child with cblB disorder who developed acute cardiomyopathy (CM). The patient presented with fever, tachycardia, and dyspnea. Echocardiography revealed depressed left ventricular function, which initially improved with standard treatment but rapidly deteriorated. Coenzyme Q10 (CoQ10) supplementation was initiated at a dose of 25 mg/kg/day, resulting in a remarkable improvement in cardiac function within 72 h. This report highlights the potential efficacy of CoQ10 in treating MMA-related cardiomyopathy, suggesting mitochondrial dysfunction as a key factor. The successful use of CoQ10 in this context is novel, as previous literature mainly focused on its application in propionic acidemia. This report proposes CoQ10 supplementation as a promising adjuvant therapy for cardiomyopathy in MMA, particularly in cblB disorder, and calls for further research to validate its benefits.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12739617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849418","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":"Retrospective Case Series of Fulminant Metabolic Crisis in GSDIA: Persistent Lactic Acidosis Despite Correction of Hypoglycemia May Reflect Secondary Mitochondrial Dysfunction","authors":"Herodes Guzman,&nbsp;Nicole Stewart,&nbsp;Lauren Mitteer,&nbsp;Victoria Sanders,&nbsp;Rebecca Ganetzky,&nbsp;Diva D. De Leon","doi":"10.1002/jmd2.70059","DOIUrl":"10.1002/jmd2.70059","url":null,"abstract":"<p>Although several advances in glycogen storage disorder (GSD) management have been made over the years, there is still increased morbidity and mortality in these patients, particularly among those with GSD type I (GSDI). Here, we describe a case series of five patients with GSDIa who presented with severe lactic acidosis and passed away without a clearly identified etiology, despite some having adequate metabolic control at baseline. Based on these presentations and emerging literature, we posit that progressive, secondary mitochondrial dysfunction plays an important role in placing GSDIa patients at increased risk for GSDI-related complications, including fulminant metabolic crisis. Both <i>G6PC1</i> knockout mice and human GSDIa plasma and urinary samples exhibit markers of mitochondrial dysfunction. Our observations of refractory lactic acidosis despite hyper- or eu-glycemia potentially suggest mitochondrial dysfunction as a unique feature of the metabolic decompensation experienced by the patients of this report. Thus, underlying mitochondrial dysfunction may set up certain GSDIa patients for multiorgan failure that is unresponsive to conventional therapies. Further research into the mitochondrial function of GSDIa patients across the lifespan is warranted. By introducing surveillance strategies for mitochondrial dysfunction in GSDI, existing antioxidant therapies could be harnessed to maintain or improve mitochondrial function in this patient population. In turn, the integration of mitochondrial therapies into GSD care may improve quality of life and avoid the development of fulminant metabolic crisis.</p>","PeriodicalId":14930,"journal":{"name":"JIMD reports","volume":"67 1","pages":""},"PeriodicalIF":1.8,"publicationDate":"2025-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12741212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145849362","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}