Gangliosidosis (Type2)(GM2)

A group of inherited metabolic disorders affecting the nervous system

GM2 Gangliosidosis
Synonyms	N/A
Pronounce	N/A
Specialty	N/A
Symptoms	Developmental delay, muscle weakness, seizures
Complications	N/A
Onset	Infancy or early childhood
Duration	N/A
Types	Tay-Sachs disease, Sandhoff disease
Causes	Genetic mutations in HEXA or HEXB genes
Risks	N/A
Diagnosis	Genetic testing, enzyme assay
Differential diagnosis	N/A
Prevention	N/A
Treatment	Supportive care, experimental therapies
Medication	N/A
Prognosis	Poor, progressive neurological decline
Frequency	N/A
Deaths	N/A

GM2 Gangliosidosis is a group of lysosomal storage disorders characterized by the accumulation of gangliosides in the nervous system. These disorders are caused by a deficiency in the enzymes responsible for the degradation of GM2 gangliosides, leading to their accumulation and resulting in progressive neurological damage.

Types

GM2 Gangliosidosis is primarily divided into two main types:

Tay-Sachs Disease

Tay-Sachs disease is caused by a deficiency of the enzyme hexosaminidase A, due to mutations in the HEXA gene. It is most commonly seen in infants, who appear normal at birth but begin to show symptoms such as developmental delay, muscle weakness, and an exaggerated startle response by 6 months of age. As the disease progresses, affected children may experience seizures, vision and hearing loss, and paralysis.

Sandhoff Disease

Sandhoff disease is similar to Tay-Sachs disease but results from a deficiency in both hexosaminidase A and B, due to mutations in the HEXB gene. It affects individuals of all ethnic backgrounds and presents with similar symptoms to Tay-Sachs disease, but often with a more rapid progression.

Pathophysiology

GM2 gangliosides are complex molecules found in the cell membranes of neurons. In GM2 Gangliosidosis, the inability to degrade these molecules leads to their accumulation, particularly in the central nervous system. This accumulation disrupts normal cellular function, leading to the progressive neurological symptoms observed in affected individuals.

Diagnosis

Diagnosis of GM2 Gangliosidosis is typically made through a combination of clinical evaluation, genetic testing, and enzyme assays. Genetic testing can identify mutations in the HEXA or HEXB genes, while enzyme assays can measure the activity of hexosaminidase A and B in blood or tissue samples.

Treatment

Currently, there is no cure for GM2 Gangliosidosis. Treatment is primarily supportive and focuses on managing symptoms and improving quality of life. This may include physical therapy, medications to control seizures, and nutritional support. Experimental therapies, such as gene therapy and enzyme replacement therapy, are being investigated as potential treatments.

Prognosis

The prognosis for individuals with GM2 Gangliosidosis is generally poor, with most affected children experiencing severe neurological decline and a reduced lifespan. The rate of progression can vary depending on the specific type and severity of the enzyme deficiency.

Also see

• Lysosomal storage disorder
• Hexosaminidase A
• Genetic testing
• Neurological disorder