Beta-mannosidosis, also called lysosomal beta-mannosidase deficiency, is a disorder of

oligosaccharide An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sugar ...

metabolism caused by decreased activity of the enzyme

beta-mannosidase Beta-mannosidase (, ''mannanase'', ''mannase'', ''beta-D-mannosidase'', ''beta-mannoside mannohydrolase'', ''exo-beta-D-mannanase'', ''lysosomal beta A mannosidase'') is an enzyme with List of enzymes, systematic name ''beta-D-mannoside mannoh ...

. This enzyme is coded for by the gene '' MANBA'', located at 4q22-25. Beta-mannosidosis is inherited in an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

manner. 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 Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signifi ...

. Hearing loss and

angiokeratomas Angiokeratoma is a benign cutaneous lesion of capillaries, resulting in small marks of red to blue color and characterized by hyperkeratosis. ''Angiokeratoma corporis diffusum'' refers to Fabry's disease, but this is usually considered a distinct c ...

are common features of the disease.

Symptoms and signs

The initial affected individual described in 1986 had a complex

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

, and was later found to have both beta-mannosidosis and Sanfilippo syndrome. 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 (

). Most cases are identified in the first year of life with

respiratory infections Respiratory tract infections (RTIs) are infectious diseases involving the respiratory tract. An infection of this type usually is further classified as an upper respiratory tract infection (URI or URTI) or a lower respiratory tract infection (LRI ...

hearing loss Hearing loss is a partial or total inability to Hearing, hear. Hearing loss may be present at birth or acquired at any time afterwards. Hearing loss may occur in one or both ears. In children, hearing problems can affect the ability to Language ...

and

. 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.subscription required

Cause

In terms of causation several

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mi ...

in the MANBA gene is the cause of beta-mannosidosis. The

cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

location of the gene is 4q24, furthermore the condition is inherited in an autosomal recessive manner

Mechanism

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

disaccharide A disaccharide (also called a double sugar or ''biose'') is the sugar formed when two monosaccharides are joined by glycosidic linkage. Like monosaccharides, disaccharides are simple sugars soluble in water. Three common examples are sucrose, lact ...

s Beta-mannosidase function is consistent with, it being a

lysosomal A lysosome () is a membrane-bound organelle found in many animal Cell (biology), cells. They are spherical Vesicle (biology and chemistry), vesicles that contain Hydrolysis, hydrolytic enzymes that can break down many kinds of biomolecules. A ly ...

enzyme catalyzing and thus involved in degradation route for N-linked

moieties(

glycoproteins Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...

)

Diagnosis

A diagnosis of beta-mannosidosis is suspected based on the persons clinical presentation.

Urine Urine is a liquid by-product of metabolism in humans and in many other animals. Urine flows from the kidneys through the ureters to the urinary bladder. Urination results in urine being excretion, excreted from the body through the urethra. Cel ...

testing to identify abnormal

oligosaccharides An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sugar ...

is a useful screening test, and enzymatic analysis or molecular testing can be used for confirmation.

Differential diagnosis

Diagnostic techniques for this condition can be done to offer a DDx, via

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar groups that are part of other molecules, so cause agglutination of particular cells or precipitation of glycoconjugates and polysaccharides. Lectins have a role in rec ...

histochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to ant ...

to distinguish between α-mannosidosis and beta-mannosidosis.

Treatment

In terms of beta-mannosidosis treatment there is none currently available, individuals that exhibit muscle weakness or

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...

are treated based on the symptoms (since there's no cure)

References

External links

{{Medicine Glycoprotein metabolism disorders Rare diseases Autosomal recessive disorders