Alpha-mannosidosis
A progressive lysosomal storage disorder from enzyme deficiency.
Alpha-mannosidosis is a lysosomal storage disorder first described by Swedish physician Okerman in 1967. It is caused by an autosomal recessive genetic mutation in the gene MAN2B1 on chromosome 19, leading to deficiency of the enzyme alpha-D-mannosidase. The disease is lifelong, multi-systemic, and progressive, with neuromuscular and skeletal deterioration over decades.
- treatment_options
- Hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (velmanase alfa, approved in the EU but not the US)
Lore & Background
Alpha-mannosidosis results from a defective alpha-mannosidase enzyme, which normally breaks down complex sugars from glycoproteins in the lysosome. This deficiency causes progressive accumulation of mannose-rich oligosaccharides in all tissues, leading to impaired cellular function and apoptosis. Complete absence of enzyme function leads to early childhood death, while low residual activity causes milder forms with hearing impairment, cognitive issues, infections, and skeletal deformities.
Reader's Guide
Alpha-mannosidosis is significant as a rare, progressive disorder with a broad clinical spectrum. Diagnosis relies on measuring residual alpha-mannosidase activity in leukocytes and genetic testing of MAN2B1. Management is proactive, focusing on complications such as hydrocephalus, hearing loss, and skeletal issues. Hematopoietic stem cell transplantation offers benefit in younger patients, and enzyme replacement therapy with velmanase alfa is approved in the European Union and the US. The disease's variability and overlap with other lysosomal disorders make early diagnosis challenging but critical for treatment options.
Did You Know?
- If both parents are carriers, each pregnancy has a 25% chance of the child developing the disease.
- In livestock, alpha-mannosidosis is caused by chronic poisoning with swainsonine from locoweed.
- The most severe form (Type 3) leads to early death from progressive central nervous system involvement.
- Enzyme replacement therapy with velmanase alfa is approved in the European Union but not by the FDA in the United States.
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