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

Mol Genet Metab. 2021 Aug;133(4):397-399. doi: 10.1016/j.ymgme.2021.06.003. Epub 2021 Jun 11.


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 ( 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.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenal Insufficiency / diagnosis*
  • Adrenal Insufficiency / etiology
  • Adrenal Insufficiency / physiopathology*
  • Adult
  • Child
  • Child, Preschool
  • Congenital Disorders of Glycosylation
  • Female
  • Glycosylation
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Phosphotransferases (Phosphomutases) / blood*
  • Phosphotransferases (Phosphomutases) / genetics
  • Pituitary-Adrenal System / physiology
  • Prospective Studies
  • Risk Factors
  • Young Adult


  • Phosphotransferases (Phosphomutases)
  • phosphomannomutase

Associated data