دورية أكاديمية
Multiple phenotypes in phosphoglucomutase 1 deficiency
| العنوان: | Multiple phenotypes in phosphoglucomutase 1 deficiency |
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| المؤلفون: | Tegtmeyer, LC, Rust, S, van Scherpenzeel, M, Ng, BG, Losfeld, ME, Timal, S, Raymond, K, He, P, Ichikawa, M, Veltman, J, Huijben, K, Shin, YS, Sharma, V, Adamowicz, M, Lammens, M, Reunert, J, Witten, A, Schrapers, E, Matthijs, G, Jaeken, J, Rymen, D, Stojkovic, T, Laforet, P, Petit, F, Aumaitre, O, Czarnowska, E, Piraud, M, Podskarbi, T, Stanley, CA, Matalon, R, Burda, P, Seyyedi, S, Debus, V, Socha, P, Sykut-Cegielska, J, van Spronsen, F, de Meirleir, L, Vajro, P, DeClue, T, Ficicioglu, C, Wada, Y, Wevers, RA, Vanderschaeghe, Dieter, Callewaert, Nico, Fingerhut, R, van Schaftingen, E, Freeze, HH, Morava, E, Lefeber, DJ, Marquardt, T |
| المصدر: | NEW ENGLAND JOURNAL OF MEDICINE ; ISSN: 0028-4793 |
| سنة النشر: | 2014 |
| المجموعة: | Ghent University Academic Bibliography |
| مصطلحات موضوعية: | Medicine and Health Sciences, MUSCLE GLYCOGENOSIS, DILATED CARDIOMYOPATHY, NUCLEOTIDE SUGARS, GLYCOSYLATION, IDENTIFICATION, CHILDREN, THERAPY, GLUCOSE, CONGENITAL DISORDERS, GLYCOGEN-STORAGE-DISEASE |
| الوصف: | Background: Congenital disorders of glycosylation are genetic syndromes that result in impaired glycoprotein production. We evaluated patients who had a novel recessive disorder of glycosylation, with a range of clinical manifestations that included hepatopathy, bifid uvula, malignant hyperthermia, hypogonadotropic hypogonadism, growth retardation, hypoglycemia, myopathy, dilated cardiomyopathy, and cardiac arrest. Methods: Homozygosity mapping followed by whole-exome sequencing was used to identify a mutation in the gene for phosphoglucomutase 1 (PGM1) in two siblings. Sequencing identified additional mutations in 15 other families. Phosphoglucomutase 1 enzyme activity was assayed on cell extracts. Analyses of glycosylation efficiency and quantitative studies of sugar metabolites were performed. Galactose supplementation in fibroblast cultures and dietary supplementation in the patients were studied to determine the effect on glycosylation. Results: Phosphoglucomutase 1 enzyme activity was markedly diminished in all patients. Mass spectrometry of transferrin showed a loss of complete N-glycans and the presence of truncated glycans lacking galactose. Fibroblasts supplemented with galactose showed restoration of protein glycosylation and no evidence of glycogen accumulation. Dietary supplementation with galactose in six patients resulted in changes suggestive of clinical improvement. A new screening test showed good discrimination between patients and controls. Conclusions: Phosphoglucomutase 1 deficiency, previously identified as a glycogenosis, is also a congenital disorder of glycosylation. Supplementation with galactose leads to biochemical improvement in indexes of glycosylation in cells and patients, and supplementation with complex carbohydrates stabilizes blood glucose. A new screening test has been developed but has not yet been validated. (Funded by the Netherlands Organization for Scientific Research and others.) Two brothers with an undefined congenital disorder of glycosylation were found to have ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://biblio.ugent.be/publication/4349577Test; http://hdl.handle.net/1854/LU-4349577Test; http://dx.doi.org/10.1056/NEJMoa1206605Test; https://biblio.ugent.be/publication/4349577/file/4349755Test |
| DOI: | 10.1056/NEJMoa1206605 |
| الإتاحة: | https://doi.org/10.1056/NEJMoa1206605Test https://biblio.ugent.be/publication/4349577Test http://hdl.handle.net/1854/LU-4349577Test https://biblio.ugent.be/publication/4349577/file/4349755Test |
| حقوق: | No license (in copyright) ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.7DDB2E58 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1056/NEJMoa1206605 |
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