Mannosidosis

Society for Mucopolysaccharide Diseases
MPS House, Repton Place, White Lion Road, Amersham, Buckinghamshire, HP7 9LP, UK
Tel: 0845 389 9901 Fax: 0845 389 9902
National Registered Charity No. 287034

Mannosidosis

Mannosidosis is a rare lysosomal storage disorder of the oligosaccharide family and closely related to the Mucopolysaccharidoses. Alpha-Mannosidosis was first described by Dr Oekermann, from Lund in Sweden, in 1967. There is another variant known as Beta-Mannosidosis which is extremely rare and has produced a wide range of clinical abnormalities in the few patients described with this disorder.

Mannosidosis is an enzyme deficiency disorder which results in defective mannosidase activity and the accumulation of mannose-rich oligosaccharide chains. This accumulation is responsible for many problems that affect individuals with Mannosidosis.

Whilst there is no cure for individuals affected by this disorder, a booklet published by the MPS Society sets out to demonstrate the presentation and clinical management of this disease. The prospect of new therapies is also addressed. The booklet draws on the experiences of parents and doctors and with reference to medical literature.

What causes Mannosidosis?
Oligosaccharides are long chains of sugar molecules used in the building of bones, cartilage, skin, tendons and many other tissues in the body. 'Oligo' means a small number and 'saccharide' is a general term for sugar molecule. In the course of normal life there is a continuous process of building new oligosaccharides and breaking down old ones - a recycling process. The breakdown and recycling process requires a series of special biochemical tools called enzymes. Children and adults with Mannosidosis are missing an enzyme called mannosidase. The incompletely broken down mannosidase remain stored inside the cells of the body and begin to build up causing progressive damage. Babies may show little sign of the disease but as more and more cells become damaged by accumulation of oligosaccharides, symptoms start to appear.

How common is Mannosidosis?
The MPS Society which co-ordinates the European Registry for Mucopolysaccharide and Related Diseases has shown that there are 8 affected individuals in the United Kingdom. Although worldwide approximately 200 cases have been reported, there are probably many more patients who are not diagnosed or reported.

Does Mannosidosis affect individuals differently?
There is a wide spectrum of severity. Some individuals with Mannosidosis will have mild to moderate learning difficulties which may develop in childhood or adolescence.

It is important to remember that Mannosidosis is extremely varied in its effects. A whole range of possible symptoms is outlined in this booklet, however affected individuals may not experience all of them.

How is Mannosidosis inherited?
Genes, inherited from our parents, control how tall we are, the colour of our eyes and skin. Some genes we inherit are 'recessive', that is to say we carry the gene but it does not have any effect on our development. Mannosidosis is caused by a recessive gene. If an adult carrying the abnormal gene has a partner who is also a carrier, there will be one in four chance with every pregnancy that the foetus will inherit the defective gene from each parent and will suffer from the disease. There is a two in three chance that unaffected brothers and sisters of those affeted by Mannosidosis will be carriers. They can be reassured however that, as the disease is so rare, the chance of having a partner who is another carrier is very slight unless the individuals are of the same family.

Can you test for Mannosidosis in Pregnancy?
If you have a child with Mannosidosis it is possible to have tests during any subsequent pregnancy to find out whether the foetus is affected. It is important to contact your doctor as soon as you suspect that you may be pregnant if you wish for tests to be arranged. Both amniocentesis and chorionic villus sampling can be used to diagnose Mannosidosis in utero.

Specific Treatment of Mannosidosis
Bone Marrow Transplant (BMT): For some years Bone Marrow Transplants (BMT) have been used to treat children with Mucopolysaccharide and related diseases. Some children with Mannosidosis have benefited from Bone Marrow Transplant, although this has not been shown to have any effect on preventing the damage to the brain that occurs in individuals severely affected by Mannosidosis.

Enzyme Replacement Therapy (ERT): Enzyme Replacement Therapy clinical trials for some MPS and related diseases are already at an advanced stage and this treatment will be available for some individuals in the near future. This will involve the recombinant enzyme being given by repeated intravenous infusion. Although there is reason to hope that Enzyme Replacement Therapy will help some of the physical problems, the blood-brain barrier may prevent Enzyme Replacement Therapy from directly helping the brain. However ERT for Mannosidosis may be a possibility in the future.

Future Treatments
There is a great deal of research being carried out that may lead to possible treatments. Gene therapy (replacing the faulty gene with a copy of a normal gene) may be a realistic possibility in years to come. It is possible that not all those affected by Mannosidosis will be able to benefit from these advances.

Your paediatrician or physician may be able to give you up to date information on treatment options or you may contact the Society for Mucopolysaccharide Diseases.

Click here to read Megan's story.