TY - JOUR
T1 - Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?
AU - Čechová, Anna
AU - Honzík, Tomáš
AU - Edmondson, Andrew C.
AU - Ficicioglu, Can
AU - Serrano, Mercedes
AU - Barone, Rita
AU - De Lonlay, Pascale
AU - Schiff, Manuel
AU - Witters, Peter
AU - Lam, Christina
AU - Patterson, Marc
AU - Janssen, Mirian C.H.
AU - Correia, Joana
AU - Quelhas, Dulce
AU - Sykut-Cegielska, Jolanta
AU - Plotkin, Horacio
AU - Morava, Eva
AU - Sarafoglou, Kyriakie
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/8
Y1 - 2021/8
N2 - 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.
AB - 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.
KW - ACTH
KW - CDG
KW - Cortisol
KW - Glycosylation
KW - Inborn errors of metabolism
KW - PMM2-CDG
KW - Phosphomannomutase 2-CDG
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U2 - 10.1016/j.ymgme.2021.06.003
DO - 10.1016/j.ymgme.2021.06.003
M3 - Article
C2 - 34140212
AN - SCOPUS:85107925583
SN - 1096-7192
VL - 133
SP - 397
EP - 399
JO - Molecular genetics and metabolism
JF - Molecular genetics and metabolism
IS - 4
ER -