Lysosomal Storage Disorder -
Genetic Brain Disorder -
Inborn Error of Metabolism and Metabolic Disorder
What is it?
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.
Some Signs and Symptoms of Type II Gm1 Gangliosidosis which begin between the ages of 1 and 5.
- Ataxia (Uncoordinated movement is due to a muscle control problem that causes an inability to coordinate
movements. It leads to a jerky, unsteady, to-and-fro motion of the middle of the body (trunk) and an unsteady
gait (walking style). It can also affect the limbs.)
- Seizures (Eli has had no seizures that we know of)
- Dementia, (Dementia is a loss of brain function that occurs with certain diseases. It affects memory, thinking,
language, judgment, and behavior.)
- Difficulties with speech (One characteristic of the late-infantile verses juvenile is that the late-infantile
usually don't develop speech, juvenile can often speak pretty well, but then lose that ability. Both Eli and
Evan have not developed understandable speech)
- Type 2 typically presents at age 1-2 years with progressive psychomotor retardation.
- Little visceromegaly (is enlargement of the internal organs in the abdomen, such as liver, spleen, stomach,
kidneys, or pancreas)
- milder skeletal disease are present compared to the infantile form
What causes Gm1 Gangliosidosis?
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. How is it inherited? GM1 gangliosidosis is inherited in an autosomal
recessive manner. Affected individuals inherit 2 mutated copies of the disease-causing gene, one from each
parent. Carrier parents (with 1 normal copy and 1 mutated copy) typically are unaffected and do not have any
signs or symptoms of the condition.
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. (it has equal sex distributions between male and female)
- It is important to note that 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 the
specific type of GM1 gangliosidosis in the family.
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 significantly alter the progression of the condition.
- Patients with Gm1 gangliosidosis are at risk for aspiration pneumonia and recurrent respiratory infections
resulting from neurologic compromise.
- Congestive heart failure may result secondary to cardiomyopathy (Cardiomyopathy is a weakening of the
heart muscle or another problem with the heart muscle. It often occurs when the heart cannot pump as well
as it should, or with other heart function problems. Most patients with cardiomyopathy have heart failure.)
- Atlantoaxial instability - Atlantoaxial instability (AAI) 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. (We know Eli has abnormally shaped vertebrae because of an MRI
we have of his spine). If this occurs, patients should be monitored, and they eventually should undergo
surgical stabilization to avoid the risk of spinal cord injury.
- Type I - Infantile - Type 1 will usually manifest 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/Juvenile - The late infantile type usually manifests within the first
2-3 years of life, often around 18 months. The juvenile form will usually manifest after age 3 to 5.
Type II progresses more slowly than type I, but still causes a shortened life expectancy. People with
the late infantile form typically survive into mid-childhood (6-12 years old), while those with the
juvenile form may live into early adulthood.
- Type 3 - Adult - Phenotypic variability is marked, but progressive development of neurologic
sequelae usually leads to a shortened lifespan.