TY - JOUR
T1 - Oral sialic acid supplementation in NANS-CDG
T2 - Results of a single center, open-label, observational pilot study
AU - den Hollander, Bibiche
AU - Brands, Marion M.
AU - de Boer, Lonneke
AU - Haaxma, Charlotte A.
AU - Lengyel, Anna
AU - van Essen, Peter
AU - Peters, Gera
AU - Kwast, Hanneke J. T.
AU - Klein, Willemijn M.
AU - Coene, Karlien L. M.
AU - Lefeber, Dirk J.
AU - van Karnebeek, Clara D. M.
N1 - Funding Information: Sialic acid was manufactured and provided by Jennewein Biotechnologie. The work of Bibiche den Hollander is supported by Stichting Metakids and United for Metabolic Diseases (UMD) ( www.umd.nl ). Publisher Copyright: © 2023 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
PY - 2023/9
Y1 - 2023/9
N2 - NANS-CDG is a congenital disorder of glycosylation (CDG) caused by biallelic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. It presents with intellectual developmental disorder (IDD), skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction. Some patients suffer progressive intellectual neurologic deterioration (PIND), emphasizing the need for a therapy. In a previous study, sialic acid supplementation in knockout nansa zebrafish partially rescued skeletal abnormalities. Here, we performed the first in-human pre- and postnatal sialic-acid study in NANS-CDG. In this open-label observational study, 5 patients with NANS-CDG (range 0–28 years) were treated with oral sialic acid for 15 months. The primary outcome was safety. Secondary outcomes were psychomotor/cognitive testing, height and weight, seizure control, bone health, gastrointestinal symptoms, and biochemical and hematological parameters. Sialic acid was well tolerated. In postnatally treated patients, there was no significant improvement. For the prenatally treated patient, psychomotor and neurologic development was better than two other genotypically identical patients (one treated postnatally, one untreated). The effect of sialic acid treatment may depend on the timing, with prenatal treatment potentially benefiting neurodevelopmental outcomes. Evidence is limited, however, and longer-term follow-up in a larger number of prenatally treated patients is required.
AB - NANS-CDG is a congenital disorder of glycosylation (CDG) caused by biallelic variants in NANS, encoding an essential enzyme in de novo sialic acid synthesis. It presents with intellectual developmental disorder (IDD), skeletal dysplasia, neurologic impairment, and gastrointestinal dysfunction. Some patients suffer progressive intellectual neurologic deterioration (PIND), emphasizing the need for a therapy. In a previous study, sialic acid supplementation in knockout nansa zebrafish partially rescued skeletal abnormalities. Here, we performed the first in-human pre- and postnatal sialic-acid study in NANS-CDG. In this open-label observational study, 5 patients with NANS-CDG (range 0–28 years) were treated with oral sialic acid for 15 months. The primary outcome was safety. Secondary outcomes were psychomotor/cognitive testing, height and weight, seizure control, bone health, gastrointestinal symptoms, and biochemical and hematological parameters. Sialic acid was well tolerated. In postnatally treated patients, there was no significant improvement. For the prenatally treated patient, psychomotor and neurologic development was better than two other genotypically identical patients (one treated postnatally, one untreated). The effect of sialic acid treatment may depend on the timing, with prenatal treatment potentially benefiting neurodevelopmental outcomes. Evidence is limited, however, and longer-term follow-up in a larger number of prenatally treated patients is required.
KW - N-acetyl-d-neuraminic acid
KW - congenital disorder of
KW - glycosylation
KW - inherited metabolic disorder
KW - intellectual developmental disorder
KW - personalized medicine
KW - sialic acid biosynthesis
UR - http://www.scopus.com/inward/record.url?scp=85164613909&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jimd.12643
DO - https://doi.org/10.1002/jimd.12643
M3 - Article
C2 - 37340906
SN - 0141-8955
VL - 46
SP - 956
EP - 971
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 5
ER -