Intact transferrin and total plasma glycoprofiling for diagnosis and therapy monitoring in phosphoglucomutase-I deficiency
Phosphoglucomutase 1 (PGM1) deficiency results in a mixed phenotype of a Glycogen Storage Disorder and a Congenital Disorder of Glycosylation (CDG). Screening for abnormal glycosylation has identified more than 40 patients, manifesting with a broad clinical and biochemical spectrum which complicates...
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| Main Authors: | , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
10 May 2018
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| In: |
Translational research
Year: 2018, Volume: 199, Pages: 62-76 |
| ISSN: | 1878-1810 |
| DOI: | 10.1016/j.trsl.2018.04.008 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1016/j.trsl.2018.04.008 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S1931524418300732 
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| Author Notes: | Nurulamin Abu Bakar, Nicol C. Voermans, Thorsten Marquardt, Christian Thiel, Mirian C.H. Janssen, Hana Hansikova, Ellen Crushell, Jolanta Sykut-Cegielska, Francis Bowling, Lars Mørkrid, John Vissing, Eva Morava, Monique van Scherpenzeel, and Dirk J. Lefeber |
| Summary: | Phosphoglucomutase 1 (PGM1) deficiency results in a mixed phenotype of a Glycogen Storage Disorder and a Congenital Disorder of Glycosylation (CDG). Screening for abnormal glycosylation has identified more than 40 patients, manifesting with a broad clinical and biochemical spectrum which complicates diagnosis. Together with the availability of D-galactose as dietary therapy, there is an urgent need for specific glycomarkers for early diagnosis and treatment monitoring. We performed glycomics profiling by high-resolution QTOF mass spectrometry in a series of 19 PGM1-CDG patients, covering a broad range of biochemical and clinical severity. Bioinformatics and statistical analysis were used to select glycomarkers for diagnostics and define glycan-indexes for treatment monitoring. Using 3 transferrin glycobiomarkers, all PGM1-CDG patients were diagnosed with 100% specificity and sensitivity. Total plasma glycoprofiling showed an increase in high mannose glycans and fucosylation, while global galactosylation and sialylation were severely decreased. For treatment monitoring, we defined 3 glycan-indexes, reflecting normal glycosylation, a lack of complete glycans (LOCGI) and of galactose residues (LOGI). These indexes showed improved glycosylation upon D-galactose treatment with a fast and near-normalization of the galactose index (LOGI) in 6 out of 8 patients and a slower normalization of the LOCGI in all patients. Total plasma glycoprofiling showed improvement of the global high mannose glycans, fucosylation, sialylation, and galactosylation status on D-galactose treatment. Our study indicates specific glycomarkers for diagnosis of mildly and severely affected PGM1-CDG patients, and to monitor the glycan-specific effects of D-galactose therapy. |
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| Item Description: | Gesehen am 03.04.2019 |
| Physical Description: | Online Resource |
| ISSN: | 1878-1810 |
| DOI: | 10.1016/j.trsl.2018.04.008 |