Alpha-Mannosidosis: Quantitative Oligosaccharide Biomarker Analysis in Dried Blood Spots for Diagnosis, Newborn Screening, and Treatment Monitoring
Diğer yayınlar > Diğer · 2026
Yazarlar: Dominik Badekow, Michelle Jeschik, Benjamin Dreyer, Katharina Hoff, Anja Friederike Köhn, Mona Lindschau, Anna Baghdasaryan, Anibh Martin Das, Simone Harmeling, Xinying Hong, Pavel Ješina, Vassiliki Konstantopoulou, Francyne Kubaski, Alexander Laemmle, Florian Lagler, Thomas Lücke, Martin Magner, Lara Maleen Marten, Neslihan Önenli Mungan, Anke Schumann, Lina Verena Sevenich, Ronen Spiegel, Marcus Stange, Ali Tunç Tuncel, Sema KALKAN UÇAR, Nicole Muschol, René Santer, Simona Murko
Diğer, Uluslararası, 2026,
Özet
Background: Alpha-mannosidosis (AM) is a debilitating lysosomal storage disorder (LSD) caused by insufficient activity of alpha-mannosidase, an enzyme responsible for cleavage of alpha-linked mannose residues from N-glycan-type oligosaccharides during their degradation. As a result, specific oligosaccharides accumulate in tissues and are also detectable in body fluids. AM is a progressive multi-organ disease for which hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are therapeutic options, however, treatment results depend considerably on early diagnosis. Therefore, inclusion of AM into newborn screening panels would significantly contribute to improving therapeutic outcome. Methods: A rapid and fully quantitative method for the specific AM oligosaccharide biomarker Man2GlcNAc in dried blood spots (DBS) using ultra-performance liquid chromatography coupled to tandem-mass spectrometry was developed. DBS from 420 controls, 27 AM patients (including five newborn screening samples), and 35 patients with other LSDs were analyzed. Results: A distinct separation in biomarker concentrations was observed between unaffected individuals and untreated AM patients (0.1 − 0.8 vs 3.2 − 11.3 μmol Man 2GlcNAc /L, p<0.0001). Furthermore, Man2GlcNAc concentrations significantly differed between untreated patients and those on ERT (n = 17, p<0.0001) or after HSCT (n = 15, p<0.0001), and between both treatment groups (p<0.0001). Moreover, we demonstrated that this method is appropriate for monitoring treatment efficacy by analysis of samples from individual patients before and after initiation of therapy. We retrospectively analyzed residual samples of dried blood spots (DBS) from routine newborn screening that had been stored from patients with later-confirmed AM, which resulted in clear separation from the concentrations observed in a newborn screening control cohort (7.7 − 11.3 vs 0.1 − 0.8 μmol Man 2GlcNAc /L, p=0.0001). Conclusion: We present a simple and rapid method for quantitative analysis of the specific AM oligosaccharide biomarker Man 2GlcNAc , which is remarkably stable compared to enzymatic assays. Thus, the method is useful for selective screening in suspected cases as well as for monitoring the response to different forms of treatment. Furthermore, Man 2GlcNAc has the potential to serve as a useful biomarker for newborn screening offering the prospect of earlier treatment initiation, improved therapeutic outcome and higher quality of life for AM patients.