Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?

Anna Čechová; Tomáš Honzík; Andrew C. Edmondson; Can Ficicioglu; Mercedes Serrano; Rita Barone; Pascale De Lonlay; Manuel Schiff; Peter Witters; Christina Lam; Marc Patterson; Mirian C.H. Janssen; Joana Correia; Dulce Quelhas; Jolanta Sykut-Cegielska; Horacio Plotkin; Eva Morava; Kyriakie Sarafoglou

doi:10.1016/j.ymgme.2021.06.003

Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?

Anna Čechová, Tomáš Honzík, Andrew C. Edmondson, Can Ficicioglu, Mercedes Serrano, Rita Barone, Pascale De Lonlay, Manuel Schiff, Peter Witters, Christina Lam, Marc Patterson, Mirian C.H. Janssen, Joana Correia, Dulce Quelhas, Jolanta Sykut-Cegielska, Horacio Plotkin, Eva Morava, Kyriakie Sarafoglou

Pediatric Endocrinology

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production. Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multi-center Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 μg/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned. Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG.

Original language	English (US)
Pages (from-to)	397-399
Number of pages	3
Journal	Molecular Genetics and Metabolism
Volume	133
Issue number	4
DOIs	https://doi.org/10.1016/j.ymgme.2021.06.003
State	Published - Aug 1 2021

Bibliographical note

Funding Information:
Several authors of this publication are also supported by the NIH U54 NS115198-01 grant.

Funding Information:
Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN) - Project ID No 739543.Several authors of this publication are also supported by the NIH U54 NS115198-01 grant.AC and TH were supported by RVO-VFN 64165 project of the Ministry of Health of the Czech Republic, TH was supported by EUROGLYCAN-omics, Ministry of Education Youth and Sports of Czech Republic No. 8F19002, under the frame of E-Rare-3, the ERA-Net for Research on Rare Diseases.MS is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194) and National Grant PI17/00101 from the National R&D&I Plan, cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research) and FEDER (European Regional Development Fund).PW was partially funded by FWO Flanders, Belgium (G049220N). P.W. is supported by the clinical research fund, University Hospitals Leuven, Leuven, Belgium.

Funding Information:
AC and TH were supported by RVO-VFN 64165 project of the Ministry of Health of the Czech Republic , TH was supported by EUROGLYCAN-omics , Ministry of Education Youth and Sports of Czech Republic No. 8F19002 , under the frame of E-Rare-3, the ERA-Net for Research on Rare Diseases.

Funding Information:
PW was partially funded by FWO Flanders , Belgium ( G049220N ). P.W. is supported by the clinical research fund, University Hospitals Leuven, Leuven, Belgium.

Funding Information:
MS is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194 ) and National Grant PI17/00101 from the National R&D&I Plan , cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research ) and FEDER ( European Regional Development Fund ).

Publisher Copyright:
© 2021 The Authors

Keywords

ACTH
CDG
Cortisol
Glycosylation
Inborn errors of metabolism
PMM2-CDG
Phosphomannomutase 2-CDG

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ymgme.2021.06.003

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Cite this

Čechová, A., Honzík, T., Edmondson, A. C., Ficicioglu, C., Serrano, M., Barone, R., De Lonlay, P., Schiff, M., Witters, P., Lam, C., Patterson, M., Janssen, M. C. H., Correia, J., Quelhas, D., Sykut-Cegielska, J., Plotkin, H., Morava, E., & Sarafoglou, K. (2021). Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency? Molecular Genetics and Metabolism, 133(4), 397-399. https://doi.org/10.1016/j.ymgme.2021.06.003

Čechová, A, Honzík, T, Edmondson, AC, Ficicioglu, C, Serrano, M, Barone, R, De Lonlay, P, Schiff, M, Witters, P, Lam, C, Patterson, M, Janssen, MCH, Correia, J, Quelhas, D, Sykut-Cegielska, J, Plotkin, H, Morava, E & Sarafoglou, K 2021, 'Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?', Molecular Genetics and Metabolism, vol. 133, no. 4, pp. 397-399. https://doi.org/10.1016/j.ymgme.2021.06.003

@article{1f0a9fe077d44b31ab3b64301be49590,

title = "Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?",

abstract = "PMM2-CDG is the most common congenital disorder of glycosylation (CDG) accounting for almost 65% of known CDG cases affecting N-glycosylation. Abnormalities in N-glycosylation could have a negative impact on many endocrine axes. There is very little known on the effect of impaired N-glycosylation on the hypothalamic-pituitary-adrenal axis function and whether CDG patients are at risk of secondary adrenal insufficiency and decreased adrenal cortisol production. Cortisol and ACTH concentrations were simultaneously measured between 7:44 am to 1 pm in forty-three subjects (20 female, median age 12.8 years, range 0.1 to 48.6 years) participating in an ongoing international, multi-center Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 μg/dl and low to normal ACTH levels, suggestive of secondary adrenal insufficiency. Two of the 11 subjects have confirmed central adrenal insufficiency and are on hydrocortisone replacement and/or stress dosing during illness; 3 had normal and 1 had subnormal cortisol response to ACTH low-dose stimulation test but has not yet been started on therapy; the remaining 5 have upcoming stimulation testing planned. Our findings suggest that patients with PMM2-CDG may be at risk for adrenal insufficiency. Monitoring of morning cortisol and ACTH levels should be part of the standard care in patients with PMM2-CDG.",

keywords = "ACTH, CDG, Cortisol, Glycosylation, Inborn errors of metabolism, PMM2-CDG, Phosphomannomutase 2-CDG",

author = "Anna {\v C}echov{\'a} and Tom{\'a}{\v s} Honz{\'i}k and Edmondson, {Andrew C.} and Can Ficicioglu and Mercedes Serrano and Rita Barone and {De Lonlay}, Pascale and Manuel Schiff and Peter Witters and Christina Lam and Marc Patterson and Janssen, {Mirian C.H.} and Joana Correia and Dulce Quelhas and Jolanta Sykut-Cegielska and Horacio Plotkin and Eva Morava and Kyriakie Sarafoglou",

note = "Funding Information: Several authors of this publication are also supported by the NIH U54 NS115198-01 grant. Funding Information: Several authors of this publication are members of the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN) - Project ID No 739543.Several authors of this publication are also supported by the NIH U54 NS115198-01 grant.AC and TH were supported by RVO-VFN 64165 project of the Ministry of Health of the Czech Republic, TH was supported by EUROGLYCAN-omics, Ministry of Education Youth and Sports of Czech Republic No. 8F19002, under the frame of E-Rare-3, the ERA-Net for Research on Rare Diseases.MS is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194) and National Grant PI17/00101 from the National R&D&I Plan, cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research) and FEDER (European Regional Development Fund).PW was partially funded by FWO Flanders, Belgium (G049220N). P.W. is supported by the clinical research fund, University Hospitals Leuven, Leuven, Belgium. Funding Information: AC and TH were supported by RVO-VFN 64165 project of the Ministry of Health of the Czech Republic , TH was supported by EUROGLYCAN-omics , Ministry of Education Youth and Sports of Czech Republic No. 8F19002 , under the frame of E-Rare-3, the ERA-Net for Research on Rare Diseases. Funding Information: PW was partially funded by FWO Flanders , Belgium ( G049220N ). P.W. is supported by the clinical research fund, University Hospitals Leuven, Leuven, Belgium. Funding Information: MS is supported by the Generalitat de Catalunya (PERIS SLT008/18/00194 ) and National Grant PI17/00101 from the National R&D&I Plan , cofinanced by the Instituto de Salud Carlos III (Subdirectorate-General for Evaluation and Promotion of Health Research ) and FEDER ( European Regional Development Fund ). Publisher Copyright: {\textcopyright} 2021 The Authors",

year = "2021",

month = aug,

day = "1",

doi = "10.1016/j.ymgme.2021.06.003",

language = "English (US)",

volume = "133",

pages = "397--399",

journal = "Biochemical Medicine and Metabolic Biology",

issn = "1096-7192",