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Genetic and Rare Diseases Information Center (GARD)

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GM1 gangliosidosis type 1


Other Names for this Disease
  • Beta galactosidase deficiency type 1
  • Gangliosidosis generalized GM1 infantile form
  • Gangliosidosis generalized GM1 type 1
  • GLB deficiency type 1
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Your Question

My son has been diagnosed with GM1 gangliosidosis. Please tell me more about this condition.

Our Answer

We have identified the following information that we hope you find helpful. If you still have questions, please contact us.

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. 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. This condition is caused by mutations in the GLB1 gene and is inherited in an autosomal recessive fashion.[2]
Last updated: 4/3/2012

What are the signs and symptoms of GM1 gangliosidosis?

There are three types of GM1 gangliosidosis. They 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 individuals with this type develop cherry-red spots in the eye. Children may become deaf and blind by one year of age.[1][3][4] Affected children typically do not live past 2 years of age.[2]

Signs and symptoms of juvenile (type 2) GM1 gangliosidosis, considered an intermediate form of the condition, may begin between the ages of 1 and 5. Features include 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 ganglioosidosis may cause signs and symptoms to develop anywhere between the ages of 3 and 30. Affected individuals may have muscle atrophy, corneal clouding and dystonia.[1][3][4] 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][3][4]
Last updated: 8/6/2012

What causes GM1 gangliosidosis?

All three types of GM1 gangliosidosis are caused by mutations (changes) in the GLB1 gene. This gene provides instructions for making an enzyme called beta-galactosidase (β-galactosidase), which plays an important role in the brain. The enzyme is located 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 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.

In general, individuals with higher enzyme activity levels usually have milder signs and symptoms than those with lower activity levels because they have less accumulation of GM1 ganglioside within the body.[2]
Last updated: 8/6/2012

How is GM1 gangliosidosis inherited?

GM1 gangliosidosis is inherited in an autosomal recessive manner.[3][4] 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. 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 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.[4]
Last updated: 8/6/2012

How might GM1 gangliosidosis be treated?

There is currently no effective medical treatment for GM1 gangliosidosis.[5] Symptomatic treatment for some of the neurologic signs and symptoms is available, but does not significantly alter the progression of the condition.[3][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.[5] Active research in the areas of enzyme replacement and gene therapy for the condition is ongoing but has not yet advanced to human trials.[3][6]

Neurologic and orthopedic sequelae may prevent adequate physical activity, but affected individuals may benefit from physical and occupational therapy.[5]

Last updated: 8/6/2012

References