Alpha-Mannosidosis: Quantitative Oligosaccharide Biomarker Analysis in Dried Blood Spots for Diagnosis, Newborn Screening, and Treatment Monitoring

Alpha-mannosidosis is a serious lysosomal storage disorder caused by deficiency of the enzyme alpha-mannosidase, which is required to break down certain sugar molecules. Without this enzyme, these molecules accumulate in tissues and body fluids. Researchers developed a new method to measure a specific biomarker called Man2GlcNAc in dried blood spots using advanced chromatography. They tested it on 420 healthy individuals, 27 patients with alpha-mannosidosis, and 35 patients with other lysosomal disorders. They found a clear difference in biomarker levels between healthy people (0.1-0.8 mol/L) and untreated patients (3.2-11.3 mol/L). The method also allows monitoring of treatment effectiveness, as biomarker levels significantly decrease after enzyme replacement therapy or hematopoietic stem cell transplantation. This method has potential for inclusion in newborn screening, which would enable earlier diagnosis and better treatment outcomes.