Alpha-Mannosidosis
Pathogenesis (Lysosomal Storage)
- Alpha-mannosidase is key to the break down of oligosaccharides that contain mannose.
- Thus, alpha-mannosidase enzyme function leads to an ability of lysosomes to break down mannose-containing oligosaccharides, resulting in abnormal oligosaccharide accumulation in lyososomes and, thus, cell death; it affects numerous organ systems.
Clinical
- Onset: Early (Infancy, if severe) to Late (Adulthood, if mild)
- Neurological manifestations: Cerebral Cortical (Cognitive Delay), Cerebellar (Ataxia), Motor (Myopathy, Gait Abnormalities, Hypotonia).
- Systemic manifestations: Characteristic Facial Features, Multifarious Skeletal Abnormalities (including osteopenia, bowing of bones, skull thickening), Cataracts, Psychiatric Features
- Neurologic Exam Findings: Cognitive Delay, Hydrocephalus with Macrocephaly, Hypotonia, Ataxia
- Survival: Infancy to adulthood.
Genetics
- MAN2B1 gene mutation.
- Autosomal recessive.
References
- Calvo, Sherri; Collins, Heather; Greenberg, Kathleen, et. al at US National Library of Medicine, Genetics Home Reference. https://ghr.nlm.nih.gov