Multiple phenotypes in phosphoglucomutase 1 deficiency.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
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Tegtmeyer Laura C, Rust Stephan, van Scherpenzeel Monique, Ng Bobby G, Losfeld Marie-Estelle, Timal Sharita, Raymond Kimiyo, He Ping, Ichikawa Mie, Veltman Joris, Huijben Karin, Shin Yoon S, Sharma Vandana, Adamowicz Maciej, Lammens Martin, Reunert Janine, Witten Anika, Schrapers Esther, Matthijs Gert, Jaeken Jaak, Rymen Daisy, Stojkovic Tanya, Laforêt Pascal, Petit François, Aumaître Olivier, Czarnowska Elzbieta, Piraud Monique, Podskarbi Teodor, Stanley Charles A, Matalon Reuben, Burda Patricie, Seyyedi Soraya, Debus Volker, Socha Piotr, Sykut-Cegielska Jolanta, van Spronsen Francjan, de Meirleir Linda, Vajro Pietro, DeClue Terry, Ficicioglu Can, Wada Yoshinao, Wevers Ron A, Vanderschaeghe Dieter, Callewaert Nico, Fingerhut Ralph, van Schaftingen Emile, Freeze Hudson H, Morava Eva, Lefeber Dirk J, Marquardt Thorsten
Аннотация
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.).