Expanding the Phenotype Spectrum of β-Mannosidosis

This is the authors' abstract. We don't add key points for this paper.

Background and Objectives: β-mannosidosis is an ultra-rare lysosomal storage disorder caused by a deficiency of β-mannosidase, which catalyzes the last step of glycoprotein degradation. Owing to the limited number of reported cases, information on the natural history of the disease and brain imaging is scarce. We report 6 new cases and review them together with all the previously reported cases in the literature. Methods: , enzyme activity, urine oligosaccharide profiles, brain MRI findings, and longitudinal MRI changes in 2 of them. We also review previously reported patients to broaden the spectrum of clinical features and identify genotype-phenotype correlations. Results: variants were identified, 61.8% were private, and 38.2% have the recurrent c.2158-2A>G variant. Neuroimaging abnormalities were reported in 40% of published cases and included cortical and subcortical atrophy, basal ganglia and white matter calcification, hydrocephalus, periventricular and subcortical white matter hyperintensities, and delayed myelination. Discussion: , may influence disease expression. β-mannosidosis should be considered as a differential diagnosis in patients with syndromic or apparently nonsyndromic hearing loss, unexplained brain hypomyelination, behavioral disturbances, and intellectual disability.