Should patients with Phosphomannomutase 2-CDG (PMM2-CDG) be screened for adrenal insufficiency?
Por:
Cechová 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 and Sarafoglou K
Publicada:
1 ago 2021
Ahead of Print:
1 jul 2021
Resumen:
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, multicenter Natural History study for PMM2-CDG (ClinicalTrials.gov Identifier: NCT03173300). Of the 43 subjects, 11 (25.6%) had cortisol below 5 Ng/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. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Filiaciones:
Cechová A:
Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Honzík T:
Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
Edmondson AC:
Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, USA
Ficicioglu C:
Division of Human Genetics, Department of Pediatrics, Children's Hospital of Philadelphia, USA
Serrano M:
Pediatric Neurology Department, Hospital Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Barcelona, Spain
U-703 Centre for Biomedical Research on Rare Diseases (CIBER-ER), Instituto de Salud Carlos III, Spain
Barone R:
Child Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
De Lonlay P:
Necker Hospital, APHP, Reference Center for Inborn Errors of Metabolism, University of Paris, Paris, France
Inserm UMR_S1163, Institut Imagine, Paris, France
Schiff M:
Necker Hospital, APHP, Reference Center for Inborn Errors of Metabolism, University of Paris, Paris, France
Witters P:
Metabolic Center, Department of Pediatrics, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium
Lam C:
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA
Division of Genetic Medicine, Department of Pediatrics, University of Washington School of Medicine, Seattle, WA, USA
Patterson M:
Department of Clinical Genomics-Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, USA
Janssen MCH:
Radboud University Medical Centre, Department of Internal Medicine, Nijmegen, the Netherlands
Correia J:
Centro Hospitalar Universitário do Porto, Porto, Portugal
Quelhas D:
Centro Hospitalar Universitário do Porto, Porto, Portugal
Sykut-Cegielska J:
Department of Inborn Errors of Metabolism and Paediatrics, the Institute of Mother and Child, Warsaw, Poland
Plotkin H:
Glycomine, Inc, San Francisco, CA, USA
Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA
Morava E:
Department of Clinical Genomics-Department of Laboratory Medicine and Pathology, Mayo Clinic, MN, USA
Sarafoglou K:
Dept. of Pediatrics - Divisions of Endocrinology and Genetics & Metabolism, Dept. of Experimental & Clinical Pharmacology, University of Minnesota, USA
Green Submitted, hybrid
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