The following information may help to address your question:
What are gangliosidoses?
The gangliosidoses are a group of
inherited metabolic diseases caused by a deficiency of the different
proteins needed to break down fatty substances called
lipids. Excess lipid materials build up to harmful levels in the central and peripheral nervous systems, particularly in nerve
cells. These genetically different disorders occur when both parents pass along the same
mutated gene that regulates these proteins.
[1]
Last updated: 4/3/2012
What is GM1 gangliosidosis?
GM1 gangliosidosis is an inherited
lysosomal storage disorder that progressively destroys nerve cells (neurons) in the brain and spinal cord. The condition may be classified into three major types based on the general age that signs and symptoms first appear: classic infantile (
type 1); juvenile (
type 2); and adult onset or chronic (
type 3). Although the types differ in severity, their features may overlap significantly. GM1 gangliosidosis is caused by
mutations in the
GLB1 gene and is inherited in an
autosomal recessive manner. Treatment is currently symptomatic and supportive.
[2][3]
Last updated: 11/17/2015
What are the signs and symptoms of GM1 gangliosidosis?
There are three general types of GM1 gangliosidosis, which differ in severity but can have considerable overlap of signs and symptoms.
[2]
- Classic infantile (type 1) GM1 gangliosidosis is the most severe type, with onset shortly after birth (usually within 6 months of age).[2] Affected infants typically appear normal until onset, but developmental regression (loss of acquired milestones) eventually occurs.[2] Signs and symptoms may include neurodegeneration, seizures, liver and spleen enlargement, coarsening of facial features, skeletal irregularities, joint stiffness, a distended abdomen, muscle weakness, an exaggerated startle response to sound, and problems with gait (manner of walking). About half of people with this type develop cherry-red spots in the eye. Children may become deaf and blind by one year of age.[1][4][5] Affected children typically do not live past 2 years of age.[2]
- Juvenile (type 2) GM1 gangliosidosis is considered an intermediate form of the condition and may begin between the ages of 1 and 5. Features include ataxia, seizures, dementia, and difficulties with speech. This type progresses more slowly than type 1, but still causes decreased life expectancy (around mid-childhood or early adulthood).[2]
- Adult (type 3) GM1 gangliosidosis may cause signs and symptoms to develop anywhere between the ages of 3 and 30. Affected people may have muscle atrophy, corneal clouding and dystonia.[1][4][5] Non-cancerous skin blemishes may develop on the lower part of the trunk of the body.[1] Adult GM1 is usually less severe and progresses more slowly than other forms of the condition.[1][4][5]
Last updated: 11/17/2015
What causes GM1 gangliosidosis?
All three types of GM1 gangliosidosis are caused by
mutations (changes) in the
GLB1 gene. This gene gives the body instructions to make an
enzyme called beta-galactosidase (β-galactosidase), which plays an important role in the brain. The enzyme resides in compartments within cells called
lysosomes, where it helps break down certain
molecules, including a substance called GM1 ganglioside. GM1 ganglioside is important for nerve cell function in the brain.
Mutations in the GLB1 gene may lower or eliminate the activity of the β-galactosidase enzyme, keeping GM1 ganglioside from being broken down. As a result, it accumulates to toxic levels in
tissues and
organs, particularly in the brain. This accumulation leads to the destruction of nerve cells, causing the features of the condition. In general, people with higher enzyme activity levels usually have milder features than those with lower activity levels.
[2]
Last updated: 11/17/2015
How is GM1 gangliosidosis inherited?
GM1 gangliosidosis is a hereditary condition that is inherited in an
autosomal recessive manner.
[4][5] This means that to be affected, a person must have a
mutation in both copies of the responsible
gene in each cell. Affected people inherit one mutated copy of the gene from each parent, who is referred to as a
carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has:
- a 25% (1 in 4) chance to be affected
- a 50% (1 in 2) chance to be an unaffected carrier like each parent
- a 25% chance to be unaffected and not be a carrier
GM1 gangliosidosis is type-specific within families. This means that people with a family history of the condition are generally only at increased risk for the specific type of GM1 gangliosidosis in the family.[5]
Last updated: 11/17/2015
How might GM1 gangliosidosis be treated?
There is currently no effective medical treatment for GM1 gangliosidosis.
[1][4] Symptomatic treatment for some of the neurologic signs and symptoms is available, but does not significantly alter the progression of the condition.
[4][6] For example, anticonvulsants may initially control seizures. Supportive treatments may include proper nutrition and hydration, and keeping the affected individual's airway open.
[1]
Bone marrow transplantation was reportedly successful in an individual with infantile/juvenile GM1 gangliosidosis; however, no long-term benefit was reported. Presymptomatic cord-blood hematopoietic stem-cell transplantation has been advocated by some as a possible treatment due to its success in other lysosomal storage disorders.[4] Active research in the areas of enzyme replacement and gene therapy for the condition is ongoing but has not yet advanced to human trials.[4][6]
Neurologic and orthopedic sequelae may prevent adequate physical activity, but affected individuals may benefit from physical and occupational therapy.[4]
Last updated: 8/6/2012
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