Alpha-mannosidosis is caused by the lack of the lysosomal enzyme alpha-mannosidase due to a mutation in MAN2B1, located on chromosome 19. Lack of alpha-mannosidase causes disturbed glycoprotein catabolism. This causes an excessively high level of mannose-rich oligosaccharides in many tissues. It is a progressive disease with mental retardation, skeletal and muscle abnormalities, recurrent infections, psychiatric symptoms, and compromised pulmonary function. Symptoms progress slowly over decades and long-term prognosis is poor. Prevalence is estimated to be from 1 per 300 000 to 1 per 1 000 000. Almost all patients suffer from hearing loss and a high incidence of accompanying autoimmune disorders (e.g. lupus erythemadoses, pancytopenia, hypothyroidism or primary biliary cirrhosis) is reported.