Peter Witters1,2, Tomas Honzik3, Eric Bauchart4, Ruqaiah Altassan5,6,7, Tiffany Pascreau8,9, Arnaud Bruneel10,11, Sandrine Vuillaumier10, Nathalie Seta10,12, Delphine Borgel8,9, Gert Matthijs13, Jaak Jaeken14,15, Wouter Meersseman16,17, David Cassiman18, Lonlay Pascale de4, Eva Morava14,19. 1. Pediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. peter.witters@uzleuven.be. 2. Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium. peter.witters@uzleuven.be. 3. Department of Pediatrics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic. 4. AP-HP, Necker University Hospital, French National Reference Centre for Inborn Errors of Metabolism, Paris, France. 5. Medical Genetic Department, Montréal Children Hospital, McGill University, Montreal, Canada. 6. Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium. 7. Department of Medical Genetics, King Faisal Specialist and Research Hospital, Riyadh, Saudi Arabia. 8. AP-HP, Hôpital Necker, Service d'Hématologie Biologique, Paris, France. 9. UMR_S1176, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France. 10. Biochemistry Department, AP-HP, Bichat Hospital, Paris, France. 11. UMR INSERM 1193, Faculty of Pharmacy, Paris-Sud University, Paris, France. 12. Biochemistry Department, Paris Descartes University, Bichat Hospital, Paris, France. 13. Center for Human Genetics, KU Leuven, Leuven, Belgium. 14. Pediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. 15. Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium. 16. Metabolic Center, University Hospitals Leuven, Leuven, Belgium. 17. Department of General Internal Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium. 18. Gastroenterology-Hepatology and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. 19. Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.
Abstract
PURPOSE: PMM2-CDG is the most common congenital disorder of glycosylation (CDG), which presents with either a neurologic or multisystem phenotype. Little is known about the longitudinal evolution. METHODS: We performed data analysis on PMM2-CDG patients' clinical features according to the Nijmegen CDG severity score and laboratory data. Seventy-five patients (28 males) were followed up from 11.0 ± 6.91 years for an average of 7.4 ± 4.5 years. RESULTS: On a group level, there was no significant evolution in overall clinical severity. There was some improvement in mobility and communication, liver and endocrine function, and strabismus and eye movements. Educational achievement and thyroid function worsened in some patients. Overall, the current clinical function, the system-specific involvement, and the current clinical assessment remained unchanged. On follow-up there was improvement of biochemical variables with (near) normalization of activated partial thromboplastin time (aPTT), factor XI, protein C, antithrombin, thyroid stimulating hormone, and liver transaminases. CONCLUSION: PMM2-CDG patients show a spontaneous biochemical improvement and stable clinical course based on the Nijmegen CDG severity score. This information is crucial for the definition of endpoints in clinical trials.
PURPOSE: PMM2-CDG is the most common congenital disorder of glycosylation (CDG), which presents with either a neurologic or multisystem phenotype. Little is known about the longitudinal evolution. METHODS: We performed data analysis on PMM2-CDG patients' clinical features according to the Nijmegen CDG severity score and laboratory data. Seventy-five patients (28 males) were followed up from 11.0 ± 6.91 years for an average of 7.4 ± 4.5 years. RESULTS: On a group level, there was no significant evolution in overall clinical severity. There was some improvement in mobility and communication, liver and endocrine function, and strabismus and eye movements. Educational achievement and thyroid function worsened in some patients. Overall, the current clinical function, the system-specific involvement, and the current clinical assessment remained unchanged. On follow-up there was improvement of biochemical variables with (near) normalization of activated partial thromboplastin time (aPTT), factor XI, protein C, antithrombin, thyroid stimulating hormone, and liver transaminases. CONCLUSION: PMM2-CDG patients show a spontaneous biochemical improvement and stable clinical course based on the Nijmegen CDG severity score. This information is crucial for the definition of endpoints in clinical trials.
Authors: Anna N Ligezka; Silvia Radenkovic; Mayank Saraswat; Kishore Garapati; Wasantha Ranatunga; Wirginia Krzysciak; Hitoshi Yanaihara; Graeme Preston; William Brucker; Renee M McGovern; Joel M Reid; David Cassiman; Karthik Muthusamy; Christin Johnsen; Saadet Mercimek-Andrews; Austin Larson; Christina Lam; Andrew C Edmondson; Bart Ghesquière; Peter Witters; Kimiyo Raymond; Devin Oglesbee; Akhilesh Pandey; Ethan O Perlstein; Tamas Kozicz; Eva Morava Journal: Ann Neurol Date: 2021-10-26 Impact factor: 10.422
Authors: Hossein Moravej; Ruqaiah Altassan; Jaak Jaeken; Gregory M Enns; Carolyn Ellaway; Shanti Balasubramaniam; Pascale De Lonlay; David Coman; Saadet Mercimek-Andrews; Peter Witters; Eva Morava Journal: JIMD Rep Date: 2019-11-25
Authors: Peter Witters; Andrew C Edmondson; Hudson H Freeze; Eva Morava; Christina Lam; Christin Johnsen; Marc C Patterson; Kimiyo M Raymond; Miao He Journal: Orphanet J Rare Dis Date: 2021-02-25 Impact factor: 4.123