Molecular genetics and metabolism最新文献

{"title":"Corrigendum to “Evaluating change in diet with pegvaliase treatment in adults with phenylketonuria: Analysis of phase 3 clinical trial data” [Molecular Genetics and Metabolism 141, Issue 3 (2024) 108122]","authors":"Fran Rohr , Barbara Burton , Anne Dee , Cary O. Harding , Joshua Lilienstein , Kristin Lindstrom , Erin MacLeod , Sarah Rose , Rani Singh , Sandra van Calcar , Kaleigh Whitehall","doi":"10.1016/j.ymgme.2024.108613","DOIUrl":"10.1016/j.ymgme.2024.108613","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 4","pages":"Article 108613"},"PeriodicalIF":3.7,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging improvement in acid sphingomyelinase deficiency on enzyme replacement therapy.","authors":"William L Simpson, Jaya Ganesh","doi":"10.1016/j.ymgme.2024.108611","DOIUrl":"https://doi.org/10.1016/j.ymgme.2024.108611","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":" ","pages":"108611"},"PeriodicalIF":3.7,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142687522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Home infusion experience in patients with Pompe disease receiving avalglucosidase alfa during three clinical trials","authors":"Jordi Díaz-Manera ,&nbsp;Derralynn Hughes ,&nbsp;Sevim Erdem-Özdamar ,&nbsp;Céline Tard ,&nbsp;Anthony Béhin ,&nbsp;Françoise Bouhour ,&nbsp;James Davison ,&nbsp;Si Houn Hahn ,&nbsp;Kristina An Haack ,&nbsp;Olivier Huynh-Ba ,&nbsp;Magali Periquet ,&nbsp;Swathi Tammireddy ,&nbsp;Nathan Thibault ,&nbsp;Tianyue Zhou ,&nbsp;Ans T. van der Ploeg","doi":"10.1016/j.ymgme.2024.108608","DOIUrl":"10.1016/j.ymgme.2024.108608","url":null,"abstract":"<div><div>During three previously reported clinical trials of avalglucosidase alfa in patients with Pompe disease, 17 out of 142 participants were considered by the investigators to be appropriate candidates for home infusion. During their respective trials, these participants received a total of 419 avalglucosidase alfa infusions at home under healthcare professional supervision. They were clinically stable with no history of moderate or severe infusion-associated reactions within at least 12 months prior to starting home infusions. As of February 25, 2022, the 15 participants with late-onset Pompe disease (LOPD) had received between 2 and 48 home infusions and the 2 participants with infantile-onset Pompe disease (IOPD) had received 19 and 20 infusions. Adverse events occurred in 8 (53 %) participants with LOPD and neither of the participants with IOPD. Seven participants with LOPD had a total of 15 non-treatment-related, non-serious adverse events. One participant with LOPD experienced infusion-associated reactions of eyelid edema and flushing during the first home infusion; both were non-serious adverse events classified as grade 1 (mild). Home infusion was later resumed for this participant. Among LOPD participants, event rates for home infusions were comparable to those for clinic infusions: overall adverse events (0.028 vs 0.039 participants with events/infusion, respectively) and adverse events classified as infusion-associated reactions (0.003 vs. 0.006, respectively). No medication errors occurred during home infusion. These data suggest that infusion of avalglucosidase alfa at home is feasible and does not compromise safety for patients who have not experienced an infusion-associated reaction during the preceding 12 months of infusions in a clinical setting. Evaluation of real-world experience with avalglucosidase alfa home infusion in countries where it is already approved is ongoing.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 4","pages":"Article 108608"},"PeriodicalIF":3.7,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mini-review on the international gyrate atrophy symposium 2023: More than meets the eye. Focus on outstanding research questions","authors":"Marion Brands ,&nbsp;Berith Balfoort ,&nbsp;Karabi Acharya ,&nbsp;Arthur Bergen ,&nbsp;Nicola Brunetti-Pierri ,&nbsp;Mark Buijs ,&nbsp;Barbara Cellini ,&nbsp;Patrick Schultink ,&nbsp;Mandeep Singh ,&nbsp;Andreas Schulze ,&nbsp;Corrie Timmer ,&nbsp;David Valle ,&nbsp;Ronald Wanders ,&nbsp;Kirmo Wartiovaara ,&nbsp;Clara van Karnebeek ,&nbsp;GACR Bird's Eye View Consortium","doi":"10.1016/j.ymgme.2024.108609","DOIUrl":"10.1016/j.ymgme.2024.108609","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 4","pages":"Article 108609"},"PeriodicalIF":3.7,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of casein glycomacropeptide on general health status in children with PKU: A randomized crossover trial","authors":"Alex Pinto ,&nbsp;Anne Daly ,&nbsp;Camille Newby ,&nbsp;Abigail Robotham ,&nbsp;Simon Heales ,&nbsp;Simon Eaton ,&nbsp;Helen Aitkenhead ,&nbsp;Kimberly Gilmour ,&nbsp;Richard Jackson ,&nbsp;Catherine Ashmore ,&nbsp;Sharon Evans ,&nbsp;Júlio Cesar Rocha ,&nbsp;Fatma Ilgaz ,&nbsp;Mary Hickson ,&nbsp;Anita MacDonald","doi":"10.1016/j.ymgme.2024.108607","DOIUrl":"10.1016/j.ymgme.2024.108607","url":null,"abstract":"<div><div>In PKU, it is suggested that casein glycomacropeptide based protein substitute (GMP) may have physiological advantage when satiety, oxidative stress, renal function and inflammation are considered. Its prebiotic properties may also help gastrointestinal (GI) tolerance.</div><div>In children with PKU, a randomized/crossover trial comparing phenylalanine-free amino acids (AA) vs GMP as the single source of protein substitute for 12-weeks in each arm was conducted. There was a 4-week wash out period with AA in-between. At baseline and end of each intervention, blood and fecal samples were taken to monitor gut health, oxidative stress, renal function, inflammatory markers and plasma amino acids. Satiety and Pediatric Quality of Life (PedsQL) GI symptoms questionnaires were completed. Usual weekly blood spots for phenylalanine and tyrosine were done.</div><div>Twelve patients (8 males; aged 4-9y) with PKU participated. GMP improved the following GI symptoms: stomach pain (<em>p</em> = 0.003), heartburn and reflux (<em>p</em> = 0.041) wind and bloating (<em>p</em> = 0.018). With GMP, there was also a trend for less constipation (<em>p</em> = 0.068), discomfort with eating (<em>p</em> = 0.065) and nausea and vomiting (<em>p</em> = 0.087). There were no changes on stool gut health markers (IgA, short chain fatty acids and fecal calprotectin). There were no statistically significant differences for renal, oxidative stress, inflammatory and gut health markers or measures of satiety except for adiponectin (<em>p</em> = 0.028) and total antioxidant capacity (<em>p</em> = 0.049), although the latter was possibly without clinical significance. Mean dried blood spot phenylalanine (Phe) was 114 μmol/L higher with GMP vs AA (<em>p</em> &lt; 0.001). There was no difference in tyrosine levels. In conclusion, GI symptoms statistically significantly improved with GMP versus AA. The Phe content of GMP may present challenges when it is used as the only protein substitute in children with classical PKU with low Phe tolerance.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 4","pages":"Article 108607"},"PeriodicalIF":3.7,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142695763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cover 2 / Ed. Board","authors":"","doi":"10.1016/S1096-7192(24)00484-0","DOIUrl":"10.1016/S1096-7192(24)00484-0","url":null,"abstract":"","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 3","pages":"Article 108600"},"PeriodicalIF":3.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"cPMP rescue of a neonate with severe molybdenum cofactor deficiency after serendipitous early diagnosis, and characterisation of a novel MOCS1 variant","authors":"Bernd C. Schwahn ,&nbsp;Claire Hart ,&nbsp;Louisa Ann Smith ,&nbsp;Anthony Hart ,&nbsp;Lynette Fairbanks ,&nbsp;Monica Arenas-Hernandez ,&nbsp;Charles Turner ,&nbsp;Alistair Horman ,&nbsp;Stewart Rust ,&nbsp;José A. Santamaria-Araujo ,&nbsp;Simon J. Mayr ,&nbsp;Günter Schwarz ,&nbsp;Mark Sharrard","doi":"10.1016/j.ymgme.2024.108598","DOIUrl":"10.1016/j.ymgme.2024.108598","url":null,"abstract":"<div><div>We report the first, and so far, only index patient with neonatal onset MoCD type A who was diagnosed and treated early enough with cPMP to avoid severe brain injury and disability. The child presented with hypoglycemia at the age of 10 h and was diagnosed because of the incidental finding of severely decreased L-cystine in plasma. Due to a high level of awareness and excellent co-operation between metabolic laboratory and clinical services, cPMP substitution could be initiated before severe encephalopathy set in, and the child subsequently had a normal motor development. The child has been continued on daily substitution with cPMP until today (age 7 years) and has shown a satisfying long-term developmental outcome. Long-term follow-up, however, revealed significant communication difficulties and cognitive abilities in the range of mild to moderate learning disability. The severity of the metabolic disease was confirmed by the extent of biochemical abnormalities and further functional characterisation of the underlying genetic variants. This case provides further evidence that cPMP substitution does significantly alter the disease course when applied early enough. Postnatal treatment in this case was not sufficient to enable an entirely normal cognitive development, despite sustained complete normalization of the biochemical abnormalities.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 4","pages":"Article 108598"},"PeriodicalIF":3.7,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progressive liver disease and dysregulated glycogen metabolism in murine GSD IX γ2 models human disease","authors":"Rebecca A. Gibson ,&nbsp;William R. Jeck ,&nbsp;Rebecca L. Koch ,&nbsp;Aarav Mehta ,&nbsp;Su Jin Choi ,&nbsp;Yajur Sriraman ,&nbsp;Deeksha Bali ,&nbsp;Sarah Young ,&nbsp;Aravind Asokan ,&nbsp;Jeong-A Lim ,&nbsp;Priya S. Kishnani","doi":"10.1016/j.ymgme.2024.108597","DOIUrl":"10.1016/j.ymgme.2024.108597","url":null,"abstract":"<div><div>Hepatic glycogen storage disease type IX γ2 (GSD IX γ2) is a severe, liver-specific subtype of GSD IX. While all patients with hepatic GSD IX present with similar symptoms, over 95 % of patients with GSD IX γ2 progress to liver fibrosis and cirrhosis. Despite disease severity, the long-term natural history of GSD IX γ2 liver disease progression is not known. Our lab previously characterized the <em>Phkg2</em>^{<em>−/−</em>} mouse model at 3 months of age, demonstrating that the mouse recapitulates the early liver disease phenotype of GSD IX γ2. To understand how liver disease progresses in GSD IX γ2, we characterized the mouse model through 24 months of age. Our study showed for the first time that GSD IX γ2 mice develop liver fibrosis that progresses to cirrhosis. Importantly, we observed that the progression of liver fibrosis is associated with an initial elevation and subsequent decrease of key GSD biomarkers – the latter being a finding that is often considered to be an improvement of disease in patients. In recognition of the unique liver fibrosis pattern and to support future therapeutic investigations using this model, we developed a novel scoring system for GSD IX γ2 mouse liver pathology. Lastly, this work introduces evidence of a dysregulated glycogen metabolism pathway which can serve as an endpoint for future therapeutic evaluation. As we await longitudinal clinical natural history data, these findings greatly expand our understanding of liver disease manifestations in GSD IX γ2 and have notable clinical applications.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 4","pages":"Article 108597"},"PeriodicalIF":3.7,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-omic analysis of a mucolipidosis II neuronal cell model uncovers involvement of pathways related to neurodegeneration and drug metabolism","authors":"Lorenzo Badenetti ,&nbsp;Seok-Ho Yu ,&nbsp;Maxwell B. Colonna ,&nbsp;Rony Hull ,&nbsp;Jennifer R. Bethard ,&nbsp;Lauren Ball ,&nbsp;Heather Flanagan-Steet ,&nbsp;Richard Steet","doi":"10.1016/j.ymgme.2024.108596","DOIUrl":"10.1016/j.ymgme.2024.108596","url":null,"abstract":"<div><div>Defining the molecular consequences of lysosomal dysfunction in neuronal cell types remains an area of investigation that is needed to understand many underappreciated phenotypes associated with lysosomal disorders. Here we characterize <em>GNPTAB</em>-knockout DAOY medulloblastoma cells using different genetic and proteomic approaches, with a focus on how altered gene expression and cell surface abundance of glycoproteins may explain emerging neurological issues in individuals with <em>GNPTAB</em>-related disorders, including mucolipidosis II (ML II) and mucolipidosis IIIα/β (ML IIIα/β). The two knockout clones characterized demonstrated all the biochemical hallmarks of this disease, including loss of intracellular glycosidase activity due to impaired mannose 6-phosphate-dependent lysosomal sorting, lysosomal cholesterol accumulation, and increased markers of autophagic dysfunction. RNA sequencing identified altered transcript abundance of several neuronal markers and genes involved in drug metabolism and transport, and neurodegeneration-related pathways. Using selective <em>exo</em>-enzymatic labeling (SEEL) coupled with proteomics to profile cell surface glycoproteins, we demonstrated altered abundance of several glycoproteins in the knockout cells. Most striking was increased abundance of the amyloid precursor protein and apolipoprotein B, indicating that loss of <em>GNPTAB</em> function in these cells corresponds with elevation in proteins associated with neurodegeneration. The implication of these findings on lysosomal disease pathogenesis and the emerging neurological manifestations of <em>GNPTAB</em>-related disorders is discussed.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 3","pages":"Article 108596"},"PeriodicalIF":3.7,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of NMDA-receptor type glutamatergic antagonists dextromethorphan or ketamine in the treatment of nonketotic hyperglycinemia: A critical reassessment","authors":"Johan L.K. Van Hove","doi":"10.1016/j.ymgme.2024.108594","DOIUrl":"10.1016/j.ymgme.2024.108594","url":null,"abstract":"<div><div>The recognition of glycine as an endogenous ligand at the allosteric activation site of the NMDA-type glutamatergic receptor led to the assumption that the excess glycine in nonketotic hyperglycinemia would result in overactivation of these receptors, and of the proposed use of inhibitors such as dextromethorphan or ketamine as a therapeutic agent. Years later it was recognized that these same receptors have an alternative endogenous activator <span>d</span>-serine, which is markedly decreased in nonketotic hyperglycinemia. This may result in underactivation of these NMDA-type glutamatergic receptors, challenging the earlier hypothesis. Clear clinical evidence of an added therapeutic benefit beyond the use of glycine reduction strategies from use of either dextromethorphan or ketamine in nonketotic hyperglycinemia has not been documented. The systematic use of these NMDA-type receptor antagonists in nonketotic hyperglycinemia should be reevaluated, particularly in light of emerging potential adverse effects.</div></div>","PeriodicalId":18937,"journal":{"name":"Molecular genetics and metabolism","volume":"143 3","pages":"Article 108594"},"PeriodicalIF":3.7,"publicationDate":"2024-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}