What is ß-Mannosidosis (Beta-Mannosidosis)?

ß-Mannosidosis is one of seven identified Glycoprotein storage diseases.

These inherited diseases are part of a larger group of disorders called Lysosomal storage diseases. Lysosomes are membrane-bound compartments found in the cells of the body. These compartments contain enzymes, which are responsible for the breakdown of many different oligosaccharides (long sugar chains.) These sugar chains are continuously made and broken down in our bodies, and this process is necessary for appropriate mental and physical development. Each enzyme in the lysosome is responsible for a certain step in the breakdown of the sugar chains.

When an enzyme is not working, it leads to the build up of the sugar chains in the lysosome. In ß-Mannosidosis, the specific enzyme that is absent is called beta-mannosidase. The build up of oligosaccharide sugars that is caused, is gradual
and interferes with the correct function of the cell. It This build up is gradual and
eventually leads to the clinical features of ß-Mannosidosis.

What are the clinical features of ß-Mannosidosis?

Individuals with ß-mannosidosis do not usually display the typical characteristics
that are usually associated with lysosomal storage diseases such as coarse
facial features, corneal changes, skeletal changes or hepatosplenomegaly (large
liver and/or spleen). Because of the absence of many of these typical features, ß-
Mannosidosis may be under diagnosed. The most consistent features of ß-
Mannosidosis are mental retardation, history of recurrent respiratory infections
and hearing loss. Some individuals may present with angiokeratomas (superficial
blood vessel dilation over which wartlike growths occur).

How is ß-Mannosidosis inherited?

ß- Mannosidosis is not contagious and cannot be "caught." It is a genetic
condition, which means that it is caused by a change in the instructions that
direct the way our bodies grow and develop. These instructions are called genes.
People have two copies of all their genes, including the gene for ß-Mannosidosis
(beta-mannosidase.) One copy is inherited from the mother in the egg, and one
from the father in the sperm.

Only when there is a change in the gene code is there a possibility that the
disease will occur. For a person to have ß-Mannosidosis, they must inherit
changes in both of their beta-mannosidase genes resulting in instructions that do
not function properly. This is known as autosomal recessive inheritance.

For a couple to have a child with ß-Mannosidosis, both parents must have at
least one changed copy of the beta-mannosidase gene which they pass on to
their child. Parents do not have control over which genes they pass on to their
children.

If a person has one changed copy of the beta-mannosidase gene and one
normal copy of the beta-mannosidase gene they are said to be a "carrier" of the
condition and will not show any symptoms of ß-Mannosidosis. If two parents are
both carriers, they have a 1 in 4 (25%) chance of having a child with ß-
Mannosidosis in each pregnancy.

What testing is available to determine if my child or I have ß- Mannosidosis?

Testing for Glycoprotein storage diseases is typically performed in conjunction
with a genetics evaluation. A genetics team takes into account the medical
history and clinical features of a patient to determine what type of genetic testing
is appropriate. For the diagnosis of an Glycoprotein storage disease, a urine
test should show increased oligosaccharides. To determine if the patient has ß-
Mannosidosis, the urine test should be followed by a blood test or skin biopsy.
The blood or skin sample should show decreased activity of the enzymes beta-
mannosidase.

For families who have had a child diagnosed with ß-Mannosidosis, prenatal
diagnosis is available in future pregnancies by looking at beta-mannosidase
activity through Chorionic Villus Sampling (CVS) or amniocentesis. Prenatal
diagnosis by detection of beta-mannosidase gene changes is also available for
families in which the responsible gene changes have been identified.

What type of treatment is available for ß-Mannosidosis?

Individuals with ß-Mannosidosis should have routine follow-up with Genetics, and
Pulmonary and ENT as indicated. Treatment is aimed at addressing the
individual problems as they arise.

For some Glycoprotein diseases, bone marrow transplant has been trialed as
an experimental therapy but there are no conclusive results on the long term
benefits. Ask your specialist for more information on this.