.2020 Sep-Oct;131(1-2):135-146.

doi: 10.1016/j.ymgme.2020.08.003. Epub 2020 Sep 17.

Phosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots

Federica Conte¹, Eva Morava², Nurulamin Abu Bakar³, Saskia B Wortmann⁴, Anne Jonge Poerink⁵, Stephanie Grunewald⁶, Ellen Crushell⁷, Lihadh Al-Gazali⁸, Maaike C de Vries⁹, Lars Mørkrid¹⁰, Jozef Hertecant¹¹, Katja S Brocke Holmefjord¹², David Kronn¹³, Annette Feigenbaum¹⁴, Ralph Fingerhut¹⁵, Sunnie Y Wong¹⁶, Monique van Scherpenzeel¹⁷, Nicol C Voermans¹⁸, Dirk J Lefeber¹⁹

Affiliations

¹ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Federica.Conte@radboudumc.nl.
² Center of Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA. Electronic address: Morava-Kozicz.Eva@mayo.edu.
³ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Nurulamin.BinAbuBakar@radboudumc.nl.
⁴ Institute of Human Genetics, Technische Universität München, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany; Department of Pediatrics, Salzburger Landeskliniken (SALK) und Paracelsus Medical University (PMU), Salzburg, Austria. Electronic address: wortmann-hagemann@helmholtz-muenchen.de.
⁵ Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Department of Pediatrics, Medisch Centrum Twente, Enschede, the Netherlands. Electronic address: A.JongePoerink@mst.nl.
⁶ Great Ormond Street Hospital Foundation Trust, UCL Institute of Child Health, London, Great Britain, UK. Electronic address: Stephanie.Grunewald@gosh.nhs.uk.
⁷ National Centre for Inherited Metabolic Disorders, Children's Health Ireland at Temple Street and Crumlin Hospitals, Dublin, Ireland. Electronic address: Ellen.Crushell@cuh.ie.
⁸ Department of Pediatrics, College of Medicine & Health Sciences, UAE University, Al-Ain, United Arab Emirates. Electronic address: l.algazali@uaeu.ac.ae.
⁹ Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. Electronic address: Maaike.deVries@radboudumc.nl.
¹⁰ Institute of Clinical Medicine, University of Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital-Rikshospitalet, Norway. Electronic address: lamo2@ous-hf.no.
¹¹ Genetics and Metabolics Service, Tawam Hospital, Al Ain, United Arab Emirates. Electronic address: jhertecant@seha.ae.
¹² Department. of Pediatric Habilitation/Department of Pediatric Neurology, Stavanger University Hospital, Stavanger, Norway. Electronic address: katja.sara.brocke.holmefjord@sus.no.
¹³ Medical Genetic, Inherited Metabolic Diseases and Lysosomal Storage Disorders Center, Boston Children Hospital, MA, USA. Electronic address: David_Kronn@bchphysicians.org.
¹⁴ Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA. Electronic address: afeigenbaum@ucsd.edu.
¹⁵ Swiss Newborn Screening Laboratory, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. Electronic address: Ralph.Fingerhut@kispi.uzh.ch.
¹⁶ Hayard Genetics Center, Tulane University School of Medicine, New Orleans, LA, United States of America. Electronic address: swong1@tulane.edu.
¹⁷ Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; GlycoMScan B.V, Oss, the Netherlands. Electronic address: monique.vanscherpenzeel@glycomscan.com.
¹⁸ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Nicol.Voermans@radboudumc.nl.
¹⁹ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Dirk.Lefeber@radboudumc.nl.

PMID:33342467
DOI: 10.1016/j.ymgme.2020.08.003

Free article

Phosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots

Federica Conte et al. Mol Genet Metab.2020 Sep-Oct.

Free article

.2020 Sep-Oct;131(1-2):135-146.

doi: 10.1016/j.ymgme.2020.08.003. Epub 2020 Sep 17.

Authors

Affiliations

¹ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Federica.Conte@radboudumc.nl.
² Center of Individualized Medicine, Department of Clinical Genomics, Mayo Clinic, Rochester, USA; Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, USA. Electronic address: Morava-Kozicz.Eva@mayo.edu.
³ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Nurulamin.BinAbuBakar@radboudumc.nl.
⁴ Institute of Human Genetics, Technische Universität München, Munich, Germany; Institute of Human Genetics, Helmholtz Zentrum München, Munich, Germany; Department of Pediatrics, Salzburger Landeskliniken (SALK) und Paracelsus Medical University (PMU), Salzburg, Austria. Electronic address: wortmann-hagemann@helmholtz-muenchen.de.
⁵ Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Department of Pediatrics, Medisch Centrum Twente, Enschede, the Netherlands. Electronic address: A.JongePoerink@mst.nl.
⁶ Great Ormond Street Hospital Foundation Trust, UCL Institute of Child Health, London, Great Britain, UK. Electronic address: Stephanie.Grunewald@gosh.nhs.uk.
⁷ National Centre for Inherited Metabolic Disorders, Children's Health Ireland at Temple Street and Crumlin Hospitals, Dublin, Ireland. Electronic address: Ellen.Crushell@cuh.ie.
⁸ Department of Pediatrics, College of Medicine & Health Sciences, UAE University, Al-Ain, United Arab Emirates. Electronic address: l.algazali@uaeu.ac.ae.
⁹ Department of Pediatrics, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands. Electronic address: Maaike.deVries@radboudumc.nl.
¹⁰ Institute of Clinical Medicine, University of Oslo, Norway; Department of Medical Biochemistry, Oslo University Hospital-Rikshospitalet, Norway. Electronic address: lamo2@ous-hf.no.
¹¹ Genetics and Metabolics Service, Tawam Hospital, Al Ain, United Arab Emirates. Electronic address: jhertecant@seha.ae.
¹² Department. of Pediatric Habilitation/Department of Pediatric Neurology, Stavanger University Hospital, Stavanger, Norway. Electronic address: katja.sara.brocke.holmefjord@sus.no.
¹³ Medical Genetic, Inherited Metabolic Diseases and Lysosomal Storage Disorders Center, Boston Children Hospital, MA, USA. Electronic address: David_Kronn@bchphysicians.org.
¹⁴ Department of Pediatrics, University of California San Diego and Rady Children's Hospital, San Diego, CA, USA. Electronic address: afeigenbaum@ucsd.edu.
¹⁵ Swiss Newborn Screening Laboratory, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland. Electronic address: Ralph.Fingerhut@kispi.uzh.ch.
¹⁶ Hayard Genetics Center, Tulane University School of Medicine, New Orleans, LA, United States of America. Electronic address: swong1@tulane.edu.
¹⁷ Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands; GlycoMScan B.V, Oss, the Netherlands. Electronic address: monique.vanscherpenzeel@glycomscan.com.
¹⁸ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Nicol.Voermans@radboudumc.nl.
¹⁹ Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands; Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Dirk.Lefeber@radboudumc.nl.

PMID:33342467
DOI: 10.1016/j.ymgme.2020.08.003

Abstract

Phosphoglucomutase 1 deficiency is a congenital disorder of glycosylation (CDG) with multiorgan involvement affecting carbohydrate metabolism, N-glycosylation and energy production. The metabolic management consists of dietary D-galactose supplementation that ameliorates hypoglycemia, hepatic dysfunction, endocrine anomalies and growth delay. Previous studies suggest that D-galactose administration in juvenile patients leads to more significant and long-lasting effects, stressing the urge of neonatal diagnosis (0-6 months of age). Here, we detail the early clinical presentation of PGM1-CDG in eleven infantile patients, and applied the modified Beutler test for screening of PGM1-CDG in neonatal dried blood spots (DBSs). All eleven infants presented episodic hypoglycemia and elevated transaminases, along with cleft palate and growth delay (10/11), muscle involvement (8/11), neurologic involvement (5/11), cardiac defects (2/11). Standard dietary measures for suspected lactose intolerance in four patients prior to diagnosis led to worsening of hypoglycemia, hepatic failure and recurrent diarrhea, which resolved upon D-galactose supplementation. To investigate possible differences in early vs. late clinical presentation, we performed the first systematic literature review for PGM1-CDG, which highlighted respiratory and gastrointestinal symptoms as significantly more diagnosed in neonatal age. The modified Butler-test successfully identified PGM1-CDG in DBSs from seven patients, including for the first time Guthrie cards from newborn screening, confirming the possibility of future inclusion of PGM1-CDG in neonatal screening programs. In conclusion, severe infantile morbidity of PGM1-CDG due to delayed diagnosis could be prevented by raising awareness on its early presentation and by inclusion in newborn screening programs, enabling early treatments and galactose-based metabolic management.

Keywords: Congenital disorder of glycosylation; Dilated cardiomyopathy; Exercise intolerance; Galactose; Hypoglycemia; PGM1.

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Conflict of interest statement

Declaration of Competing Interest The authors have no conflicts of interest to disclose.

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Phosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots

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Phosphoglucomutase-1 deficiency: Early presentation, metabolic management and detection in neonatal blood spots

Authors

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Conflict of interest statement

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