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Figure 1. Clinical manifestations in Alpha-Mannosidosis. The figure shows the location of the clinical manifestations of AM within the
human body. Cognitive function impairment and psychosis are features affecting all these patients.

Figure 2. MRI brain scans of an adult patient with Alpha-Mannosidosis. The MRI scans depicted in the figures show subtle diffuse
supratentorial deep white matter changes, as well as cerebellar atrophy within the brain of a 32-year-old untreated patient with AM,
who has mild learning difficulties and new-onset psychosis.

Secondary mitochondrial dysfunction may arise in these patients, consequent on their defective lysosomal
function, which has been observed in several other LSDs [9,10] . Secondary mitochondrial dysfunction, in
addition to endoplasmic reticulum (ER) stress, can lead to reactive oxygen species (ROS) accumulation.
ROS molecules contain a minimum of one oxygen atom and one or more unpaired electrons that are
produced in small quantities under normal physiological conditions . However, when produced in excess,
[11]
they cause oxidative stress to occur within the cell, in turn leading to cellular damage and has been shown to
[11]
have particular adverse effects on the nervous system .