What is GM1 Gangliosidosis?
GM1 gangliosidosis is an inherited lysosomal storage disorder that progressively destroys nerve cells
(neurons) in the brain and spinal cord. Some researchers classify this condition into three major types
based on the age at which signs and symptoms first appear. The three types include: classic infantile
(type 1), juvenile (type 2), and adult onset or chronic (type 3). Although the three types differ in
severity, their features can overlap significantly. Because of this overlap, other researchers believe
that GM1 gangliosidosis represents a continuous disease spectrum instead of three distinct types.
Signs and Symptoms
- Ataxia which is uncoordinated movement is due to a muscle control problem that causes an inability to coordinate
- Dementia or loss of brain function which affects memory, thinking,
language, judgment, and behavior
- Difficulties with speech
- Progressive psychomotor retardation
- Little visceromegaly which is enlargement of the internal organs in the abdomen, such as liver, spleen, stomach,
kidneys, or pancreas
- Milder skeletal disease can be present in the infantile form
What causes it?
Mutations in the GLB1 gene may decrease or eliminate the activity of the β-galactosidase enzyme, which means
that the GM1 ganglioside cannot be broken down. As a result, it accumulates to toxic levels in tissues and organs,
particularly in the brain. This accumulation then leads to the destruction of nerve cells in the brain, which
causes the features of the condition.
Galactosidases are enzymes that breakdown GM1, and the failure to remove GM1 results in GM1 gangliosidosis.
GM1 gangliosidosis are inherited disorders that progressively destroys neurons in the brain and spinal cord as GM1
accumulates. Without treatment, this results in developmental decline and muscle weakness, eventually leading to
severe retardation and death.
Likelihood of manifestation
- When 2 carriers of an autosomal recessive condition have children, each child has a 25% (1 in 4)
risk to have the condition, a 50% (1 in 2) risk to be a carrier like each of the parents, and a 25%
risk to not have the condition and not be a carrier.
- GM1 gangliosidosis is type-specific within families. This means that
individuals with a family history of the condition are generally only at increased risk for that
How is it treated?
There is currently no effective medical treatment for GM1 Gangliosidosis. Symptomatic treatment for some
of the neurologic signs and symptoms is available, but does not yet significantly alter the progression of the condition.
- Aspiration pneumonia
- Respiratory infections
- Congestive heart failure
- Atlantoaxial instability which is characterized by excessive movement
at the junction between the atlas (C1) and axis (C2) as a result of either a bony or ligamentous
abnormality. Neurologic symptoms occur when the spinal cord is involved. AAI can develop because of
abnormally shaped cervical vertebrae.
- Type I - Infantile - manifestation within the first 6 months of life: Death usually
occurs during the second year of life because of infection and cardiopulmonary failure.
- Type 2 - Late Infantile - manifestation within the first
2-3 years of life: Patients typically survive into mid-childhood (6-12 years old).
- Type 2 - Juvenile - manifestation after age 3 to 5: Patients may live into early adulthood.
- Type 3 - Adult - Phenotypic variability is marked, but progressive development of neurologic
sequelae usually leads to a shortened lifespan.