OBJECTIVE: To define phenotypic groups and identify predictors of disease severity in patients with phosphoglucomutase-1 deficiency (PGM1-CDG). STUDY DESIGN: We evaluated 27 patients with PGM1-CDG who were divided into 3 phenotypic groups, and group assignment was validated by a scoring system, the Tulane PGM1-CDG Rating Scale (TPCRS). This scale evaluates measurable clinical features of PGM1-CDG. We examined the relationship between genotype, enzyme activity, and TPCRS score by using regression analysis. Associations between the most common clinical features and disease severity were evaluated by principal component analysis. RESULTS: We found a statistically significant stratification of the TPCRS scores among the phenotypic groups (P < .001). Regression analysis showed that there is no significant correlation between genotype, enzyme activity, and TPCRS score. Principal component analysis identified 5 variables that contributed to 54% variance in the cohort and are predictive of disease severity: congenital malformation, cardiac involvement, endocrine deficiency, myopathy, and growth. CONCLUSIONS: We established a scoring algorithm to reliably evaluate disease severity in patients with PGM1-CDG on the basis of their clinical history and presentation. We also identified 5 clinical features that are predictors of disease severity; 2 of these features can be evaluated by physical examination, without the need for specific diagnostic testing and thus allow for rapid assessment and initiation of therapy.

Biochemical Diseases Mater Children's Hospital South Brisbane Queensland Australia

Biochemistry and Chemistry Departments University of Missouri Columbia MO

Centre for Metabolic Diseases University Hospital Gasthuisberg Herestraat Leuven Belgium

Department of Genetics Washington University School of Medicine Saint Louis MO

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

Department of Neurology Radboudumc Nijmegen The Netherlands

Department of Pediatric Habilitation Stavanger University Hospital Stavanger Norway

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

Department of Pediatrics Radboud University Nijmegen Medical Center Nijmegen The Netherlands

Department of Pediatrics Universitair Ziekenhuis Leuven Leuven Belgium

Department of Pediatrics University of Münster Münster Germany

Hayward Genetics Center Tulane University School of Medicine New Orleans LA

Hayward Genetics Center Tulane University School of Medicine New Orleans LA; Department of Pediatrics Radboud University Nijmegen Medical Center Nijmegen The Netherlands

National Consultant in Paediatric Metabolic Medicine Screening Department The Institute of Mother and Child Warsaw Poland

Pediatric Cardiology Bergisch Gladbacher Köln Germany

Pediatric Endocrinology The Children's Hospital of Philadelphia Philadelphia PA

Sackler Faculty of Medicine Tel Aviv University Tel Aviv Yafo Israel

Salzburger Landeskliniken Department of Pediatrics Paracelsus Medical University Salzburg Austria

Citace poskytuje Crossref.org

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