In:
Journal of Inherited Metabolic Disease, Wiley, Vol. 46, No. 2 ( 2023-03), p. 313-325
Abstract:
Congenital disorders of glycosylation (CDG) are a clinically and biochemically heterogeneous subgroup of inherited metabolic disorders. Most CDG with abnormal N‐glycosylation can be detected by transferrin screening, however, MOGS‐CDG escapes this routine screening. Combined with the clinical heterogeneity of reported cases, diagnosing MOGS‐CDG can be challenging. Here, we clinically characterize ten MOGS‐CDG cases including six previously unreported individuals, showing a phenotype characterized by dysmorphic features, global developmental delay, muscular hypotonia, and seizures in all patients and in a minority vision problems and hypogammaglobulinemia. Glycomics confirmed accumulation of a Glc 3 Man 7 GlcNAc 2 glycan in plasma. For quantification of the diagnostic Glcα1‐3Glcα1‐3Glcα1‐2Man tetrasaccharide in urine, we developed and validated a liquid chromatography‐mass spectrometry method of 2‐aminobenzoic acid (2AA) labeled urinary glycans. As an internal standard, isotopically labeled 13 C 6 ‐2AA Glc 3 Man was used, while labeling efficiency was controlled by use of 12 C 6 ‐2AA and 13 C 6 ‐2AA labeled laminaritetraose. Recovery, linearity, intra‐ and interassay coefficients of variability of these labeled compounds were determined. Furthermore, Glc 3 Man was specifically identified by retention time matching against authentic MOGS‐CDG urine and compared with Pompe urine. Glc 3 Man was increased in all six analyzed cases, ranging from 34.1 to 618.0 μmol/mmol creatinine (reference 〈 5 μmol). In short, MOGS‐CDG has a broad manifestation of symptoms but can be diagnosed with the use of a quantitative method for analysis of urinary Glc 3 Man excretion.
Type of Medium:
Online Resource
ISSN:
0141-8955
,
1573-2665
Language:
English
Publisher:
Wiley
Publication Date:
2023
detail.hit.zdb_id:
2006875-X
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