Шаблон:Infobox medical condition (new)Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency,[1] is a disorder of oligosaccharide metabolism caused by decreased activity of the enzyme beta-mannosidase. This enzyme is coded for by the gene MANBA, located at 4q22-25. Beta-mannosidosis is inherited in an autosomal recessive manner.[1] Affected individuals appear normal at birth, and can have a variable clinical presentation. Infantile onset forms show severe neurodegeneration, while some children have intellectual disability. Hearing loss and angiokeratomas are common features of the disease.[2][3]
The initial affected individual described in 1986 had a complex phenotype, and was later found to have both beta-mannosidosis and Sanfilippo syndrome.[1] People have been described with a wide spectrum of clinical presentations, from infants and children with intellectual disability to adults who present with isolated skin findings (angiokeratomas).[1]
Most cases are identified in the first year of life with respiratory infections, hearing loss and intellectual disability. Because of its rarity, and non-specific clinical findings, beta-mannosidosis can go undiagnosed until adulthood, where it can present with intellectual disability and behavioral problems, including aggression.[4][5]
Cause
In terms of causation, several mutations in the MANBA gene are the cause of beta-mannosidosis. The cytogenetic location of the gene is 4q24; furthermore, the condition is inherited in an autosomal recessive manner.[6][3]
The pathophysiology of this condition is better comprehended if one first looks at the normal function of beta-mannosidase, such as its function of breaking down disaccharides.Шаблон:Medical citation needed
Beta-mannosidase function is consistent with it being a lysosomal enzyme catalyzing and thus involved in degradation route for N-linked oligosaccharide moieties (glycoproteins).[7]
A diagnosis of beta-mannosidosis is suspected based on the person's clinical presentation. Urine testing to identify abnormal oligosaccharides is a useful screening test, and enzymatic analysis or molecular testing can be used for confirmation.[2]
