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

oligosaccharide An oligosaccharide (; ) is a carbohydrate, saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including Cell–cell recognition, cell recognition and ce ...

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 In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

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 (in the United States), Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010).Archive is a generalized neurodevelopmental ...

. Hearing loss and angiokeratomas 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 (physical form and structure), its developmental processes, its biochemical and physiological propert ...

, and was later found to have both beta-mannosidosis and

Sanfilippo syndrome Sanfilippo syndrome, also known as mucopolysaccharidosis type III (MPS III), is a rare lifelong genetic disease that mainly affects the brain and spinal cord. It is caused by a problem with how the body breaks down certain large sugar molecules ...

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

respiratory infections Respiratory tract infections (RTIs) are infectious diseases involving the lower or upper 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 ...

hearing loss Hearing loss is a partial or total inability to 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 acquire spo ...

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, mitosi ...

in the MANBA gene are 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

manner.

Mechanism

Beta-mannosidase function is consistent with it being a

lysosomal A lysosome () is a membrane-bound organelle that is found in all mammalian cells, with the exception of red blood cells (erythrocytes). There are normally hundreds of lysosomes in the cytosol, where they function as the cell’s degradation cent ...

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

moieties (

glycoproteins Glycoproteins are proteins which contain oligosaccharide (sugar) 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 a ...

Diagnosis

A diagnosis of beta-mannosidosis is suspected based on the person's clinical presentation.

Urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

testing to identify abnormal

oligosaccharides An oligosaccharide (; ) is a saccharide polymer containing a small number (typically three to ten) of monosaccharides (simple sugars). Oligosaccharides can have many functions including cell recognition and cell adhesion. They are normally presen ...

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

differential diagnosis In healthcare, a differential diagnosis (DDx) is a method of analysis that distinguishes a particular disease or condition from others that present with similar clinical features. Differential diagnostic procedures are used by clinicians to di ...

, via

lectin Lectins are carbohydrate-binding proteins that are highly specific for sugar Moiety (chemistry), groups that are part of other molecules, so cause agglutination (biology), agglutination of particular cells or precipitation of glycoconjugates an ...

histochemistry Immunohistochemistry is a form of immunostaining. It involves the process of selectively identifying antigens in cells and tissue, by exploiting the principle of antibodies binding specifically to antigens in biological tissues. Albert Hewett ...

, to distinguish between

alpha-mannosidosis Alpha-mannosidosis is a lysosomal storage disorder, first described by Swedish physician Okerman in 1967.''Malm D, Nilssen O (2008). "Alpha-mannosidosis". Orphanet J Rare Dis. 3 (1): 21. PubMed Central, PMC 2515294 . PubMed Identifier, PMID 1 ...

and beta-mannosidosis.

Treatment

There is currently no treatment available; individuals exhibiting muscle weakness or

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

are treated based on symptoms.

References

External links

{{Authority control Glycoprotein metabolism disorders Rare diseases Autosomal recessive disorders