title: Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency.
abstract: To define phenotypic groups and identify predictors of disease severity in patients with phosphoglucomutase-1 deficiency (PGM1-CDG).
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA. Electronic address: swong1@tulane.edu.
authors.forename: Sunnie Yan-Wai
authors.initials: SY
authors.lastname: Wong
authors.affiliation: Biochemistry and Chemistry Departments, University of Missouri, Columbia, MO.
authors.forename: Lesa J
authors.initials: LJ
authors.lastname: Beamer
authors.affiliation: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA.
authors.forename: Therese
authors.initials: T
authors.lastname: Gadomski
authors.affiliation: Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
authors.forename: Tomas
authors.initials: T
authors.lastname: Honzik
authors.affiliation: Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Miski
authors.initials: M
authors.lastname: Mohamed
authors.affiliation: Salzburger Landeskliniken, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Saskia B
authors.initials: SB
authors.lastname: Wortmann
authors.affiliation: Department of Pediatric Habilitation, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Katja S
authors.initials: KS
authors.lastname: Brocke Holmefjord
authors.affiliation: Department of Pediatric Habilitation, Stavanger University Hospital, Stavanger, Norway.
authors.forename: Marit
authors.initials: M
authors.lastname: Mork
authors.affiliation: Biochemical Diseases, Mater Children's Hospital, South Brisbane, Queensland, Australia.
authors.forename: Francis
authors.initials: F
authors.lastname: Bowling
authors.affiliation: National Consultant in Paediatric Metabolic Medicine, Screening Department, The Institute of Mother and Child, Warsaw, Poland.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Sykut-Cegielska
authors.affiliation: Pediatric Cardiology, Bergisch Gladbacher Köln, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Koch
authors.affiliation: Pediatric Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Ackermann
authors.affiliation: Pediatric Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, PA.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Stanley
authors.affiliation: Department of Pediatrics, Universitair Ziekenhuis Leuven, Leuven, Belgium.
authors.forename: Daisy
authors.initials: D
authors.lastname: Rymen
authors.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.
authors.forename: Avraham
authors.initials: A
authors.lastname: Zeharia
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
authors.forename: Moeen
authors.initials: M
authors.lastname: Al-Sayed
authors.affiliation: Department of Pediatrics, University of Münster, Münster, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Marquardt
authors.affiliation: Centre for Metabolic Diseases, University Hospital Gasthuisberg, Herestraat, Leuven, Belgium.
authors.forename: Jaak
authors.initials: J
authors.lastname: Jaeken
authors.affiliation: Department of Neurology, Radboudumc, Nijmegen, The Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lefeber
authors.affiliation: Department of Genetics, Washington University School of Medicine, Saint Louis, MO.
authors.forename: Donald F
authors.initials: DF
authors.lastname: Conrad
authors.affiliation: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA.
authors.forename: Tamas
authors.initials: T
authors.lastname: Kozicz
authors.affiliation: Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA; Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: Eva
authors.initials: E
authors.lastname: Morava
mesh_terms: D000293:Adolescent; D000328:Adult; D000465:Algorithms; D002648:Child; D002675:Child, Preschool; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006008:Glycogen Storage Disease / Q000175:diagnosis* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D010733:Phosphoglucomutase / Q000172:deficiency / Q000235:genetics; D010808:Physical Examination; D025341:Principal Component Analysis; D012044:Regression Analysis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D005819:Genetic Markers; C488050:PGM1 protein, human; D010733:Phosphoglucomutase
keywords: bifid uvula; cleft palate; coagulopathy; congenital disorder of glycosylation; congenital malformation; dilated cardiomyopathy; hepatopathy; hormonal deficiency; hypoglycemia; myopathy; small stature