Alpha-mannosidosis is an autosomal recessive, pan-ethnic disease caused by pathogenic variants in the gene MAN2B1. The clinical presentation is highly variable and may be divided into three types: People with type 1 disease, which is the mildest, begin exhibiting symptoms after 10 years of age. They typically have slowly progressive muscle disease and mild or moderate intellectual disability. The moderate form of the disease is known as type 2, and it is the most common. Children with type 2 disease exhibit symptoms before 10 years of age. Symptoms include intellectual disability, ataxia (loss of coordination), low muscle tone, hearing loss, frequent infections, skeletal abnormalities, and distinctive facial features. Type 3 is a severe form of the disease. Individuals with type 3 have a faster progression of central nervous system and muscle disease, are more susceptible to infections, and may die in infancy or childhood. Currently, it is not possible to predict the type of disease or severity of symptoms based on the inherited variants.
For information about carrier frequency and residual risk, please see the Expanded Carrier Screen brochure.