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An ultra-rare progressive disease

What causes alpha-mannosidosis—and what is its long-term impact on patients?

A lysosomal storage disorder caused by α-mannosidase deficiency.2,3

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Alpha-mannosidosis is a recessive disorder caused by gene variants in MAN2B1, which leads to a deficiency in α-mannosidase.3

Due to the reduced activity of α-mannosidase, mannose-rich oligosaccharides accumulate in lysosomes.3,4

This leads to impaired cellular function throughout the body and a continuum of clinical manifestations.3

How rare is ultra-rare?

The incidence of alpha-mannosidosis is estimated at 1 in 500,000 to 1,000,000 live births.2

Incidence may be higher than previously thought. A genetic study of 1,010 individuals with a mucopolysaccharidosis (MPS)-like phenotype found a higher-than-expected number of alpha-mannosidosis cases.5

Clinical signs and symptoms associated with alpha-mannosidosis


Development at 20-30 years of age. Result of cerebral atrophy and cerebral demyelination.

Cognitive impairment6

Delayed development of speech. Delayed motor or mental function. IQ of 60-80 and a declining tendency over time.

Hearing loss4

Both conductive and sensorineural. Significantly affects 100% of patients over the age of 3 (hearing aids).

Recurrent infections2

Infections are especially common in the first 10 years of life. Most common infections: upper airway, pulmonary, and acute/serous otitis media.


Leading to frequent infections (middle ear, gastrointestinal, and respiratory).

Skeletal abnormalities4

Affects 92% of adult patients and 62% of pediatric patients: joint contractures, scoliosis, genua valga, and hip dysplasia.


May develop in the first year of life.

Ophthalmological abnormalities4

Corneal clouding, cataract, partial blindness due to retinal pigmentary degeneration.

Coarse facial features6

All patients show some degree of: short neck, large head with prominent forehead, rounded eyebrows, flattened nasal bridge, widely-spaced teeth, enlarged tongue.

Dental abnormalities6

Reduced dental quality, frequent cavities, tooth-grinding.

Cardiac involvement4

Cardiovascular system abnormalities in 24% of pediatric patients and 17% of adult patients.

Pulmonary involvement4

In younger patients, a decrease in pulmonary function over time.

Muscle weakness6

A factor in slow development of motor functions and uncoordinated movement.

Impaired endurance4

Physical impairment revealed in the 6-minute walk and 3-minute stair-climbing tests, correlated with oligosaccharide level.

Alpha-mannosidosis is a progressive disease.
Early identification and timely treatment is critical.7

How to identify the broad range of symptoms that could signify alpha-mannosidosis3,4,6

Know the symptoms—the most common symptoms of alpha-mannosidosis are4,6:

Hearing impairment Speech delays Skeletal abnormalities Cognitive impairment

Know what to look for—the physical signs of alpha-mannosidosis are6:

Enlarged head Short neck Prominent brow ridge
Broad, flattened nose Prominent forehead Thick tongue