General description

α-mannosidosis is an autosomal recessive disorder caused by mutations in MAN2B1 on chromosome 19, leading to α-mannosidase deficiency and the lysosomal accumulation of mannose-rich oligosaccharides. Secondary mitochondrial dysfunction may contribute to neurological decline. The disease presents with progressive intellectual disability, motor delay, ataxia, spastic paraplegia, sensorineural hearing loss, and psychiatric symptoms such as psychosis and aggression. Systemic features include coarse facial features, skeletal abnormalities like scoliosis, immunodeficiency, and cataracts. Symptoms typically appear in early childhood and worsen over time, with no clear distinction between subtypes.

β-mannosidosis results from MANBA mutations causing β-mannosidase deficiency, which leads to urinary excretion of mannose-rich oligosaccharides. The disorder manifests in childhood with intellectual disability, developmental delay, behavioral abnormalities like obsessive-compulsive traits, and seizures, sometimes appearing in the neonatal period. Systemic features include hearing loss, facial dysmorphism, recurrent infections, and erythromelalgia.

Other imaging characteristics

In addition to atrophy and white matter changes, skull thickening and sinus hypoplasia are also observed.

References

1. Majovska, Jitka, et al. "White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis." Molecular Genetics and Metabolism 132.3 (2021): 189-197.
2. Dewsbury, Mollie R., et al. "Molecular basis of neurocognitive dysfunction and psychosis in Alpha-Mannosidosis." Journal of Translational Genetics and Genomics 8.2 (2024): 85-101.