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.
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,
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
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 ...
. 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.
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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
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.
[
]
Mechanism
Beta-mannosidase function is consistent with it being a lysosomal enzyme catalyzing and thus involved in degradation route for N-linked 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 ...
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.
See also
* Beta-mannosidase
The Lost Enzyme Project
References
Further reading
*
*
External links
{{Authority control
Glycoprotein metabolism disorders
Rare diseases
Autosomal recessive disorders