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Dörfel, D.* ; Dreyer, B.* ; Lindschau, M.* ; Barbato, A.* ; Altavilla, N.* ; la Marca, G.* ; Marten, L.M.* ; Bürger, F.* ; Botti, M.* ; Sevenich, L.V.* ; Spiegel, R.* ; Schumann, A.* ; Herrmann, M.* ; Fielitz, D.* ; Muschol, N.* ; Santer, R. ; Murko, S.*

Quantification of specific urinary oligosaccharide biomarkers for diagnosis and treatment monitoring of alpha-mannosidosis.

J. Inherit. Metab. Dis. 49:e70208 (2026)
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Alpha-mannosidosis (AM, OMIM# 248500), an ultra-rare lysosomal storage disorder (LSD), is caused by insufficient activity of alpha-mannosidase, an enzyme involved in degradation of N-glycan oligosaccharides. Hence, specific oligosaccharides accumulate in tissues, resulting in a progressive multi-organ disease. Therapeutic options exist but treatment outcome depends on early diagnosis. Thus, multiple methods have been developed for analysis of these oligosaccharides in urine that are qualitative or semi-quantitative, limiting their use for treatment monitoring. A rapid quantitative method without derivatization was developed for AM biomarkers GlcNAc(Man)2, GlcNAc(Man)3, and GlcNAc(Man)4 in spot urine samples using ultra-performance liquid chromatography coupled to tandem-mass spectrometry. Urine samples of 208 controls, 20 AM patients, and 26 patients with other LSDs were analyzed. Method validation proved high recoveries (88%–108%) and precisions (standard deviation < 8%), low limits of quantification (0.12 μg GlcNAc(Man)2/mL), and high sample stability. We observed a clear separation between controls and AM patients (0.0–9.0 vs 39.4–99.3 μmol GlcNAc(Man)2/mmol creatinine, p < 0.0001). Furthermore, GlcNAc(Man)2 concentration showed significant differences between untreated patients and those treated with enzyme replacement therapy (ERT; n = 13, p = 0.0006) or hematopoietic stem cell transplantation (HSCT; n = 3, p = 0.0143), and between both treatments (p = 0.0143). Thus, the developed method is well-suited for selective screening for AM and offers a simple way to monitor treatment efficacy.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Alpha-mannosidosis ; Lc–ms/ms ; Lysosomal Storage Disorder ; Man2b1 ; Oligosaccharide ; Urine; Tandem Mass-spectrometry
ISSN (print) / ISBN 0141-8955
e-ISSN 1573-2665
Journal Journal of Inherited Metabolic Disease
Quellenangaben Volume: 49, Issue: 3, Pages: , Article Number: e70208 Supplement: ,
Publisher Wiley
Publishing Place 111 River St, Hoboken 07030-5774, Nj Usa
Reviewing status Peer reviewed
Institute(s) Institute of Human Genetics (IHG)
Grants Chiesi Farmaceutici