What is alpha-mannosidosis?
Every cell in your body has structures called lysosomes, which is where the cell breaks down the waste products from cellular activity. The lysosome is often referred to as the cell’s recycling center because it processes this waste material into substances that the cell can utilize. Lysosomes break down this unwanted matter using enzymes, which are highly specialized proteins. These enzymes are essential for breaking down the waste products.
Luke is missing an enzyme called alpha-mannosidase, which means his cells are not able to break down sugar waste products. Because the sugars are not broken down, over time the waste builds up in the lysosomes, and the lysosomes grow. This growth of the lysosomes causes the cells not to function correctly, affecting the cells differently and leading to a variety of seemingly unrelated symptoms. Because the lysosomes store these waste products, the class of disorder is known as a “Lysosome storage disorder”.
How did Luke get it?
Alpha-mannosidosis is an inherited genetic disorder. Both of Luke’s parents (Robin and Kevin) are carriers of a single copy of the defective gene, but they are not affected by the disorder. Luke received both copies of the defective gene (one from each parent) meaning he does not have the right gene (MAN2B1) for his body to produce the alpha-mannosidase enzyme.
How common is it?
It is extremely rare. The occurrence is somewhere between 1 and 2 in 1,000,000 people. As far as we know, Luke is one of 3 cases in Canada and the lab that tested this has not seen a case for 15-20 years. This means that most of the doctors we are dealing with have not seen this condition before. We have had some contact with other families who have children with alpha-mannosidosis, in England, Canada the US and New Zealand.
What are the effects of Alpha-mannosidosis?
The disorder affects every cell in Luke’s body, so the symptoms are varied and affect many aspects of Luke’s health and development. Different cells respond to the build up of waste product in the lysosomes in different ways. The disorder is progressive, so the effects become more severe over time. Because there are so few cases and the progression is different for every case, we don’t know what the rate of this progression will be for Luke. The most important effects on Luke are:
The cells in Luke’s hearing centres are impacted, and he has a moderate-severe hearing loss. He wears hearing aids to help with this.
- Ear Fluid:
Luke is susceptible to fluid build up in his ears, which further impacts his hearing. He has had 4 surgeries to implant tubes in his ears to help drain the fluid, which has helped significantly.
Luke has reduced numbers of white blood cells, meaning he has a weakened immune system. He is more susceptible to infections and gets colds and infections more often, and for longer than normal.
Luke’s bones build up more quickly, and so he has a bigger head, forehead, prominent sternum and thicker bones throughout his body. He is also at risk for osteoporosis, which we will need to monitor.
Luke’s muscles are weaker and have lower muscle tone, meaning he is not as athletic as his peers. He has some gross-motor, co-ordination and balance issues, and gets tired easily. His fine-motor skills are also affected, making it harder to hold a pencil, cut with scissors and perform other fine motor activities.
There is a build up of material in the joints, as well as destruction of cartilage over time. In later years, the joints become painful and arthritic and Luke may need a wheelchair for mobility.
The cells in the brain are also affected. The cerebellum is affected, affecting balance and co-ordination. Luke will also have some degree of mental impairment, which will affect his learning and require extra support at school.
- Life expectancy
People with alpha-manosidosis, have a reduced life expectancy. Some children with the severe form die in infancy, while those with a milder form live well into adulthood.
Is it treatable?
There is no cure at this time; treatment is limited to reducing or controlling the symptoms. Because the condition is so rare, there is not a lot of information on this condition, or the treatment. Currently there are two ideas for potential treatments:
- Enzyme replacement therapy:
The missing enzyme is artificially manufactured and then intravenously introduced into the body, eventually getting to the cells and allowing the cells to break down the waste products. This therapy has been developed for some other lysosome storage disorders, but has thus far only been tested on mice for alpha-mannosidosis. At present, it appears that this therapy is many years away for treating alpha-mannosidosis. It is also not clear that the enzyme would be able to reach the cells in the bones or the brain, since the enzymes are very large molecules.
- Bone marrow transplants:
This is currently the only therapy that has been tried for treating alpha-mannosidosis, and we are aware of only 24 patients worldwide that have had it done to treat alpha-mannosidosis. Blood is manufactured in the bone marrow, and the purpose of this treatment is to replace Luke’s bone marrow, with bone marrow from a donor, capable of producing the alpha-mannosidase enzyme. Luke’s bone marrow would be destroyed with chemotherapy and/or radiation therapy, and then bone marrow from a donor would be implanted (like a blood transfusion) to take the place of Luke’s bone marrow. The donor’s bone marrow would then start making blood cells with the missing enzyme, allowing Luke’s body to break down the waste products in his cells. It appears there has been some success with this treatment, but it is a very invasive and risky procedure. We are in contact with a number of families that have had this procedure and are discussing the outcomes that they have experienced.
What can we do?
We are getting excellent care at BC Children’s hospital. We are seeing many doctors from many different departments to discuss various options for treatment of the disorder and the symptoms. Luke will need extra support at school, which we are applying for through his school. The most important thing is to understand what Luke has, and how it affects him, and being sensitive to the special needs he might have. He is still the happy, loveable boy we all know, and we don’t want this to change the way he is treated, or how people act with him.