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.

AP HP Hôpital Necker Service d'Hématologie Biologique Paris France

AP HP Necker University Hospital French National Reference Centre for Inborn Errors of Metabolism Paris France

Biochemistry Department AP HP Bichat Hospital Paris France

Biochemistry Department Paris Descartes University Bichat Hospital Paris France

Center for Human Genetics KU Leuven Leuven Belgium

Department of Clinical Genomics Mayo Clinic Rochester MN USA

Department of Development and Regeneration Faculty of Medicine KU Leuven Leuven Belgium

Department of General Internal Medicine Faculty of Medicine KU Leuven Leuven Belgium

Department of Medical Genetics King Faisal Specialist and Research Hospital Riyadh Saudi Arabia

Department of Pediatrics 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Pediatrics University Hospitals Leuven Leuven Belgium

Gastroenterology Hepatology and Metabolic Center University Hospitals Leuven Leuven Belgium

Medical Genetic Department Montréal Children Hospital McGill University Montreal Canada

Metabolic Center University Hospitals Leuven Leuven Belgium

Pediatrics and Metabolic Center University Hospitals Leuven Leuven Belgium

UMR INSERM 1193 Faculty of Pharmacy Paris Sud University Paris France

UMR_S1176 INSERM Univ Paris Sud Université Paris Saclay Le Kremlin Bicêtre France

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