{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:50:29Z","timestamp":1792144229666,"version":"4.4.0"},"reference-count":37,"publisher":"American Society for Clinical Investigation","issue":"24","funder":[{"name":"Brain Canada Foundation and Health Canada","award":["PSG14-3505"],"award-info":[{"award-number":["PSG14-3505"]}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","award":["RGPIN 05389-14"],"award-info":[{"award-number":["RGPIN 05389-14"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"crossref","award":["#26233"],"award-info":[{"award-number":["#26233"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000233","name":"Genome BC","doi-asserted-by":"crossref","award":["SOF-195"],"award-info":[{"award-number":["SOF-195"]}],"id":[{"id":"10.13039\/501100000233","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["#301221"],"award-info":[{"award-number":["#301221"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["PJT-148863"],"award-info":[{"award-number":["PJT-148863"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Rare Diseases Network Foundation","award":["27R21814"],"award-info":[{"award-number":["27R21814"]}]},{"name":"Informatics infrastructure was supported by Genome BC and Genome Canada","award":["ABC4DE Project"],"award-info":[{"award-number":["ABC4DE Project"]}]},{"name":"ZONMW","award":["40-00506-98-9001"],"award-info":[{"award-number":["40-00506-98-9001"]}]},{"name":"VIDI Grant","award":["91713359"],"award-info":[{"award-number":["91713359"]}]},{"name":"European Union\u2019s Horizon 2020 research and innovation program","award":["ERA-NET Cofund action N\u00b0 643578."],"award-info":[{"award-number":["ERA-NET Cofund action N\u00b0 643578."]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,20]]},"abstract":"<jats:p>\n                    Sialic acids are important components of glycoproteins and glycolipids essential for cellular communication, infection, and metastasis. The importance of sialic acid biosynthesis in human physiology is well illustrated by the severe metabolic disorders in this pathway. However, the biological role of sialic acid catabolism in humans remains unclear. Here, we present evidence that sialic acid catabolism is important for heart and skeletal muscle function and development in humans and zebrafish. In two siblings, presenting with sialuria, exercise intolerance\/muscle wasting, and cardiac symptoms in the brother, compound heterozygous mutations [chr1:182775324C&gt;T (c.187C&gt;T; p.Arg63Cys) and chr1:182772897A&gt;G (c.133A&gt;G; p.Asn45Asp)] were found in the\n                    <jats:italic>N<\/jats:italic>\n                    -acetylneuraminate pyruvate lyase gene (NPL). In vitro, NPL activity and sialic acid catabolism were affected, with a cell-type-specific reduction of\n                    <jats:italic>N<\/jats:italic>\n                    -acetyl mannosamine (ManNAc). A knockdown of NPL in zebrafish resulted in severe skeletal myopathy and cardiac edema, mimicking the human phenotype. The phenotype was rescued by expression of wild-type human NPL but not by the p.Arg63Cys or p.Asn45Asp mutants. Importantly, the myopathy phenotype in zebrafish embryos was rescued by treatment with the catabolic products of NPL:\n                    <jats:italic>N<\/jats:italic>\n                    -acetyl glucosamine (GlcNAc) and ManNAc; the latter also rescuing the cardiac phenotype. In conclusion, we provide the first report to our knowledge of a human defect in sialic acid catabolism, which implicates an important role of the sialic acid catabolic pathway in mammalian muscle physiology, and suggests opportunities for monosaccharide replacement therapy in human patients.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.122373","type":"journal-article","created":{"date-parts":[[2018,12,19]],"date-time":"2018-12-19T11:02:38Z","timestamp":1545217358000},"source":"Crossref","is-referenced-by-count":55,"title":["Sialic acid catabolism by N-acetylneuraminate pyruvate lyase is essential for muscle function"],"prefix":"10.1172","volume":"3","author":[{"given":"Xiao-Yan","family":"Wen","sequence":"first","affiliation":[{"name":"Zebrafish Centre for Advanced Drug Discovery and Keenan Research Centre for Biomedical science, Li Ka Shing Knowledge Institute, St. Michael\u2019s Hospital, Toronto, Ontario, Canada."},{"name":"Department of Medicine, Physiology, Laboratory Medicine and Pathobiology and Institute of Medical Science, Faculty of Medicine, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4472-8584","authenticated-orcid":true,"given":"Maja","family":"Tarailo-Graovac","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Department of Pathology and Laboratory Sciences, BC Children\u2019s Hospital Research Institute, University of British Columbia, Vancouver, Canada."},{"name":"Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada."},{"name":"Institute of Physiology and Biochemistry, Faculty of Biology, The University of Belgrade, Belgrade, Serbia."},{"name":"Departments of Biochemistry, Molecular Biology, and Medical Genetics, Cumming School of Medicine, Alberta Children\u2019s Hospital Research Institute, University of Calgary, Calgary, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koroboshka","family":"Brand-Arzamendi","sequence":"additional","affiliation":[{"name":"Zebrafish Centre for Advanced Drug Discovery and Keenan Research Centre for Biomedical science, Li Ka Shing Knowledge Institute, St. Michael\u2019s Hospital, Toronto, Ontario, Canada."},{"name":"Department of Medicine, Physiology, Laboratory Medicine and Pathobiology and Institute of Medical Science, Faculty of Medicine, University of Toronto, Ontario, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Willems","sequence":"additional","affiliation":[{"name":"Department of Neurology, Donders Institute for Brain, Cognition, and Behavior, Radboud University Medical Center, Nijmegen, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojana","family":"Rakic","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Department of Pathology and 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