Beta-mannosidosis

Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency,^[5] 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.^[5] 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.^[3][2]

Beta-mannosidosis
Other names	Beta-mannosidase deficiency, MANSB
This condition is autosomal recessive in inheritance
Specialty	Medical genetics
Symptoms	Respiratory infections, Hearing loss and Intellectual disability.[1]
Causes	Mutations in the MANBA gene[2]
Diagnostic method	Urine test[3]
Treatment	Based on symptoms[4]

Symptoms and signs

Angiokeratoma

The initial affected individual described in 1986 had a complex phenotype, and was later found to have both beta-mannosidosis and Sanfilippo syndrome.^[5] 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).^[5]

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.^[6][1]

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.^[7][2]

Mechanism

Mannose

Beta-mannosidase function is consistent with it being a lysosomal enzyme catalyzing and thus involved in degradation route for N-linked oligosaccharide moieties (glycoproteins).^[8]

Diagnosis

Urine test

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.^[3]

Differential diagnosis

Diagnostic techniques for this condition can be done to offer a differential diagnosis, via lectin histochemistry, to distinguish between alpha-mannosidosis and beta-mannosidosis.^[9]

Treatment

There is currently no treatment available; individuals exhibiting muscle weakness or seizures are treated based on symptoms.^[4]

See also

• Beta-mannosidase
• The Lost Enzyme Project