文章基本信息

标题：The fate of orally administered sialic acid: First insights from patients with N-acetylneuraminic acid synthase deficiency and control subjects
本地全文：下载
作者：Christel Tran ; Licia Turolla ; Diana Ballhausen 等
期刊名称：Molecular Genetics and Metabolism Reports
印刷版ISSN：2214-4269
出版年度：2021
卷号：28
页码：100777
DOI：10.1016/j.ymgmr.2021.100777
出版社：Elsevier B.V.
摘要：Background 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. Methods 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. Results 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. Discussion 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.
关键词：Sialic acid ; NANS deficiency ; Developmental delay ; Nutrition therapy ; Brain gangliosides