Results of A 12-Month Prospective Study For The Frequency of Α-Mannosidosis Within Mps Like Phenotype Patients

Alfa-Mannosidosis is an inherited ultra-rare disorder in which certain glycoproteins can´t be broken down due to alfa-mannosidase deficiency resulting in oligosaccharides building up in the lysosome damaging organs and tissues. Individuals affected by alpha-Mannosidosis suffer from similar clinical symptoms as patients with mucopolysaccharidoses (MPS), such as respiratory infections, and skeletal changes. The diagnostic tests are limited due to the lack of patient population. Our medical laboratory has accredited the test, α-mannosidase activity in DBS by tandem mass spectrometry. As previously revealed by a retrospective analysis of >1000 DBS submitted for MPS diagnostics, the frequency of alpha-Mannosidosis within this sample cohort of symptomatic patients suspected of MPS is high (4 within >1000 cases), even when in an additional second study (only ~400 samples from Germany), no additional case has been identified. Due to this higher-than-expected frequency, a prospective study was initiated in September 2022 in collaboration with Chiesi. Up to date, we have evaluated α-mannosidase activity over 2,500 DBS samples from Europe and the Middle East which turned out to be negative for MPSI, MPS-II, MPS-IIIb, MPS-IVa, MPS VI, and MPS VII. The results of the 12 months of this prospective pilot study genetically confirmed 14 alpha-Mannosidosis patients up to date. This easy-to-access diagnostic test will be a valuable tool for the diagnosis of the disease allowing patients rapid access to novel treatment therapy, a better understanding of the disease pathogenesis, medical awareness, and therapeutic monitoring.