The fate of orally administered sialic acid: First insights from patients with N-acetylneuraminic acid synthase deficiency and control subjects.
Détails
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Accès restreint UNIL
Etat: Public
Version: de l'auteur⸱e
Licence: CC BY-NC-ND 4.0
ID Serval
serval:BIB_965C3E713BFF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The fate of orally administered sialic acid: First insights from patients with N-acetylneuraminic acid synthase deficiency and control subjects.
Périodique
Molecular genetics and metabolism reports
ISSN
2214-4269 (Print)
ISSN-L
2214-4269
Statut éditorial
Publié
Date de publication
09/2021
Peer-reviewed
Oui
Volume
28
Pages
100777
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
In NANS deficiency, biallelic mutations in the N-acetylneuraminic acid synthase (NANS) gene impair the endogenous synthesis of sialic acid (N-acetylneuraminic acid) leading to accumulation of the precursor, N-acetyl mannosamine (ManNAc), and to a multisystemic disorder with intellectual disability. The aim of this study was to determine whether sialic acid supplementation might be a therapeutic avenue for NANS-deficient patients.
Four adults and two children with NANS deficiency and four adult controls received oral NeuNAc acid (150 mg/kg/d) over three days. Total NeuNAc, free NeuNAc and ManNAc were analyzed in plasma and urine at different time points.
Upon NeuNAc administration, plasma free NeuNAc increased within hours (P < 0.001) in control and in NANS-deficient individuals. Total and free NeuNAc concentrations also increased in the urine as soon as 6 h after beginning of oral administration in both groups. NeuNAc did not affect plasma and urinary ManNAc, that remained higher in NANS deficient subjects than in controls (day 1-3; all P < 0.01). Oral NeuNAc was well tolerated with no significant side effects.
Orally administered free NeuNAc was rapidly absorbed but also rapidly excreted in the urine. It did not change ManNAc levels in either patients or controls, indicating that it may not achieve enough feedback inhibition to reduce ManNAc accumulation in NANS-deficient subjects. Within the limitations of this study these results do not support a potential for oral free NeuNAc in the treatment of NANS deficiency but they provide a basis for further therapeutic approaches in this condition.
Four adults and two children with NANS deficiency and four adult controls received oral NeuNAc acid (150 mg/kg/d) over three days. Total NeuNAc, free NeuNAc and ManNAc were analyzed in plasma and urine at different time points.
Upon NeuNAc administration, plasma free NeuNAc increased within hours (P < 0.001) in control and in NANS-deficient individuals. Total and free NeuNAc concentrations also increased in the urine as soon as 6 h after beginning of oral administration in both groups. NeuNAc did not affect plasma and urinary ManNAc, that remained higher in NANS deficient subjects than in controls (day 1-3; all P < 0.01). Oral NeuNAc was well tolerated with no significant side effects.
Orally administered free NeuNAc was rapidly absorbed but also rapidly excreted in the urine. It did not change ManNAc levels in either patients or controls, indicating that it may not achieve enough feedback inhibition to reduce ManNAc accumulation in NANS-deficient subjects. Within the limitations of this study these results do not support a potential for oral free NeuNAc in the treatment of NANS deficiency but they provide a basis for further therapeutic approaches in this condition.
Mots-clé
Genetics, Molecular Biology, Endocrinology, Brain gangliosides, Developmental delay, NANS deficiency, Nutrition therapy, Sialic acid
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/07/2021 10:33
Dernière modification de la notice
04/09/2021 6:34