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] |
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]
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]
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]
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.[ 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). [8]
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]
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]
There is currently no treatment available; individuals exhibiting muscle weakness or seizures are treated based on symptoms. [4]
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] |
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]
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]
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]
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.[ 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). [8]
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]
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]
There is currently no treatment available; individuals exhibiting muscle weakness or seizures are treated based on symptoms. [4]