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J Pediatr. 2016 Aug;175:130-136.e8. doi: 10.1016/j.jpeds.2016.04.021. Epub 2016 May 17.

Defining the Phenotype and Assessing Severity in Phosphoglucomutase-1 Deficiency.

Author information

1
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA. Electronic address: swong1@tulane.edu.
2
Biochemistry and Chemistry Departments, University of Missouri, Columbia, MO.
3
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA.
4
Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
5
Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
6
Salzburger Landeskliniken, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.
7
Department of Pediatric Habilitation, Stavanger University Hospital, Stavanger, Norway.
8
Biochemical Diseases, Mater Children's Hospital, South Brisbane, Queensland, Australia.
9
National Consultant in Paediatric Metabolic Medicine, Screening Department, The Institute of Mother and Child, Warsaw, Poland.
10
Pediatric Cardiology, Bergisch Gladbacher Köln, Germany.
11
Pediatric Endocrinology, The Children's Hospital of Philadelphia, Philadelphia, PA.
12
Department of Pediatrics, Universitair Ziekenhuis Leuven, Leuven, Belgium.
13
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel.
14
Department of Medical Genetics, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
15
Department of Pediatrics, University of Münster, Münster, Germany.
16
Centre for Metabolic Diseases, University Hospital Gasthuisberg, Herestraat, Leuven, Belgium.
17
Department of Neurology, Radboudumc, Nijmegen, The Netherlands.
18
Department of Genetics, Washington University School of Medicine, Saint Louis, MO.
19
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA; Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.

Abstract

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.

KEYWORDS:

bifid uvula; cleft palate; coagulopathy; congenital disorder of glycosylation; congenital malformation; dilated cardiomyopathy; hepatopathy; hormonal deficiency; hypoglycemia; myopathy; small stature

PMID:
27206562
DOI:
10.1016/j.jpeds.2016.04.021
[Indexed for MEDLINE]

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