Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?

doi:10.1038/s41436-018-0301-4

. 2019 May;21(5):1181-1188.

doi: 10.1038/s41436-018-0301-4. Epub 2018 Oct 8.

Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?

Peter Witters^{1

2}, Tomas Honzik³, Eric Bauchart⁴, Ruqaiah Altassan^{5

6

7}, Tiffany Pascreau^{8

9}, Arnaud Bruneel^{10

11}, Sandrine Vuillaumier¹⁰, Nathalie Seta^{10

12}, Delphine Borgel^{8

9}, Gert Matthijs¹³, Jaak Jaeken^{14

15}, Wouter Meersseman^{16

17}, David Cassiman¹⁸, Lonlay Pascale de⁴, Eva Morava^{14

19}

Affiliations

¹ Pediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. peter.witters@uzleuven.be.
² Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium. peter.witters@uzleuven.be.
³ Department of Pediatrics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁴ AP-HP, Necker University Hospital, French National Reference Centre for Inborn Errors of Metabolism, Paris, France.
⁵ Medical Genetic Department, Montréal Children Hospital, McGill University, Montreal, Canada.
⁶ Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
⁷ Department of Medical Genetics, King Faisal Specialist and Research Hospital, Riyadh, Saudi Arabia.
⁸ AP-HP, Hôpital Necker, Service d'Hématologie Biologique, Paris, France.
⁹ UMR_S1176, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
¹⁰ Biochemistry Department, AP-HP, Bichat Hospital, Paris, France.
¹¹ UMR INSERM 1193, Faculty of Pharmacy, Paris-Sud University, Paris, France.
¹² Biochemistry Department, Paris Descartes University, Bichat Hospital, Paris, France.
¹³ Center for Human Genetics, KU Leuven, Leuven, Belgium.
¹⁴ Pediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
¹⁵ Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium.
¹⁶ Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
¹⁷ Department of General Internal Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium.
¹⁸ Gastroenterology-Hepatology and Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
¹⁹ Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.

PMID: 30293989
DOI: 10.1038/s41436-018-0301-4

Free article

Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?

Peter Witters et al. Genet Med. 2019 May.

Free article

. 2019 May;21(5):1181-1188.

doi: 10.1038/s41436-018-0301-4. Epub 2018 Oct 8.

Authors

Affiliations

¹ Pediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium. peter.witters@uzleuven.be.
² Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium. peter.witters@uzleuven.be.
³ Department of Pediatrics, First Faculty of Medicine, Charles University and General University Hospital, Prague, Czech Republic.
⁴ AP-HP, Necker University Hospital, French National Reference Centre for Inborn Errors of Metabolism, Paris, France.
⁵ Medical Genetic Department, Montréal Children Hospital, McGill University, Montreal, Canada.
⁶ Department of Pediatrics, University Hospitals Leuven, Leuven, Belgium.
⁷ Department of Medical Genetics, King Faisal Specialist and Research Hospital, Riyadh, Saudi Arabia.
⁸ AP-HP, Hôpital Necker, Service d'Hématologie Biologique, Paris, France.
⁹ UMR_S1176, INSERM, Univ. Paris-Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.
¹⁰ Biochemistry Department, AP-HP, Bichat Hospital, Paris, France.
¹¹ UMR INSERM 1193, Faculty of Pharmacy, Paris-Sud University, Paris, France.
¹² Biochemistry Department, Paris Descartes University, Bichat Hospital, Paris, France.
¹³ Center for Human Genetics, KU Leuven, Leuven, Belgium.
¹⁴ Pediatrics and Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
¹⁵ Department of Development and Regeneration, Faculty of Medicine, KU Leuven, Leuven, Belgium.
¹⁶ Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
¹⁷ Department of General Internal Medicine, Faculty of Medicine, KU Leuven, Leuven, Belgium.
¹⁸ Gastroenterology-Hepatology and Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
¹⁹ Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.

PMID: 30293989
DOI: 10.1038/s41436-018-0301-4

Abstract

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.

Keywords: CDG severity scale; PMM2-CDG; coagulation; liver function test; long-term follow-up.

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References

1. Jaeken J, Peanne R. What is new in CDG? J Inherit Metab Dis. 2017;40:569–586. - DOI
1. Schiff M, Roda C, Monin ML, et al. Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature. J Med Genet. 2017;54:843–851.
1. Funke S, Gardeitchik T, Kouwenberg D, et al. Perinatal and early infantile symptoms in congenital disorders of glycosylation. Am J Med Genet A. 2013;161A:578–584. - DOI
1. Kjaergaard S, Kristiansson B, Stibler H, et al. Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A. Acta Paediatr. 1998;87:884–888. - DOI
1. Mayatepek E, Kohlmuller D. Mannose supplementation in carbohydrate-deficient glycoprotein syndrome type I and phosphomannomutase deficiency. Eur J Pediatr. 1998;157:605–606. - DOI

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[1] Jaeken J, Peanne R. What is new in CDG? J Inherit Metab Dis. 2017;40:569–586. - DOI

[2] Jaeken J, Peanne R. What is new in CDG? J Inherit Metab Dis. 2017;40:569–586. - DOI

[3] Schiff M, Roda C, Monin ML, et al. Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature. J Med Genet. 2017;54:843–851.

[4] Schiff M, Roda C, Monin ML, et al. Clinical, laboratory and molecular findings and long-term follow-up data in 96 French patients with PMM2-CDG (phosphomannomutase 2-congenital disorder of glycosylation) and review of the literature. J Med Genet. 2017;54:843–851.

[5] Funke S, Gardeitchik T, Kouwenberg D, et al. Perinatal and early infantile symptoms in congenital disorders of glycosylation. Am J Med Genet A. 2013;161A:578–584. - DOI

[6] Funke S, Gardeitchik T, Kouwenberg D, et al. Perinatal and early infantile symptoms in congenital disorders of glycosylation. Am J Med Genet A. 2013;161A:578–584. - DOI

[7] Kjaergaard S, Kristiansson B, Stibler H, et al. Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A. Acta Paediatr. 1998;87:884–888. - DOI

[8] Kjaergaard S, Kristiansson B, Stibler H, et al. Failure of short-term mannose therapy of patients with carbohydrate-deficient glycoprotein syndrome type 1A. Acta Paediatr. 1998;87:884–888. - DOI

[9] Mayatepek E, Kohlmuller D. Mannose supplementation in carbohydrate-deficient glycoprotein syndrome type I and phosphomannomutase deficiency. Eur J Pediatr. 1998;157:605–606. - DOI

[10] Mayatepek E, Kohlmuller D. Mannose supplementation in carbohydrate-deficient glycoprotein syndrome type I and phosphomannomutase deficiency. Eur J Pediatr. 1998;157:605–606. - DOI

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Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?

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Long-term follow-up in PMM2-CDG: are we ready to start treatment trials?

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