What are the other Names for this Condition? (Also known as/Synonyms)

• Adult GM1 Gangliosidosis
• Beta-Galactosidase Deficiency Type 3
• Gangliosidosis Generalized GM1, Chronic type

What is GM1 Gangliosidosis Type 3? (Definition/Background Information)

• 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)
  • Adult-onset or chronic (type 3)
• Although the types differ in severity, their features may overlap significantly
• GM1 Gangliosidosis Type 3 is caused by mutations in the GLB1 gene and is inherited in an autosomal recessive manner
• The treatment of GM1 Gangliosidosis Type 3 is currently symptomatic and supportive

(Source: GM1 Gangliosidosis Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets GM1 Gangliosidosis Type 3? (Age and Sex Distribution)

• GM1 Gangliosidosis Type 3 is a very rare congenital disorder, with only about 70 cases being reported in the medical literature
• The presentation of symptoms can occur at any age
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected. However, most individuals with GM1 Gangliosidosis are of Japanese origin

What are the Risk Factors for GM1 Gangliosidosis Type 3? (Predisposing Factors)

• A positive family history may be an important risk factor, since GM1 Gangliosidosis Type 3 can be inherited
• Currently, no other risk factors have been clearly identified for this disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of GM1 Gangliosidosis Type 3? (Etiology)

• GM1 Gangliosidosis Type 3 is a genetic disorder that occurs due to mutation(s) involving the GLB1 gene. This gene codes for the enzyme beta-galactosidase
• The condition is inherited in an autosomal recessive manner

Autosomal recessive pattern of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of GM1 Gangliosidosis Type 3?

The signs and symptoms of GM1 Gangliosidosis Type 3 may include:

• Abnormality of blood and blood-forming tissues
• Abnormality of the face
• Anterior beaking of lumbar vertebrae
• Decreased beta-galactosidase activity
• Diffuse cerebral atrophy
• Flared iliac wings
• Foam cells
• Hypoplastic acetabulae
• Kyphosis
• Opacification of the corneal stroma
• Platyspondyly
• Skeletal muscle atrophy
• Slurred speech

(Source: GM1 Gangliosidosis Type 3; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is GM1 Gangliosidosis Type 3 Diagnosed?

GM1 Gangliosidosis Type 3 is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing to check for or confirm GLB1 gene mutation(s)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of GM1 Gangliosidosis Type 3?

The complications of GM1 Gangliosidosis Type 3 may include:

• Progressive deterioration of vision
• Extreme pain due to bone deformities
• Difficulty with movement
• Epileptic fits, which may cause falls and injury
• Loss of speech

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is GM1 Gangliosidosis Type 3 Treated?

There is no cure for GM1 Gangliosidosis Type 3, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can GM1 Gangliosidosis Type 3 be Prevented?

Currently, GM1 Gangliosidosis Type 3 may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of GM1 Gangliosidosis Type 3? (Outcomes/Resolutions)

• The prognosis of GM1 Gangliosidosis Type 3 is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for GM1 Gangliosidosis Type 3:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/