GM2A

GM2A is a gene in humans that encodes the GM2 ganglioside activator protein. This protein is crucial for the catabolism of gangliosides; it is a cofactor necessary for the activity of the enzyme beta-hexosaminidase A. Beta-hexosaminidase A is responsible for the degradation of GM2 gangliosides, and its activity is significantly reduced in the absence of the GM2A protein. Mutations in the GM2A gene can lead to a rare inherited disorder known as GM2 gangliosidosis, type AB, characterized by an accumulation of GM2 gangliosides in the neurons, leading to neurodegeneration.

Function

The GM2A gene product is a small glycoprotein that acts as a lipid transfer protein. It facilitates the interaction between the lysosomal enzyme beta-hexosaminidase A and its substrate, the GM2 ganglioside. This interaction is essential for the hydrolysis of GM2 gangliosides into GM3 gangliosides. The process is critical for the normal turnover of gangliosides in the brain and other tissues.

Clinical Significance

Mutations in the GM2A gene are associated with GM2 gangliosidosis, type AB. This condition is part of a group of metabolic disorders known as lysosomal storage diseases. Patients with GM2 gangliosidosis type AB typically present in infancy with progressive neurological deterioration, including developmental delay, motor weakness, and seizures. The disease is progressive and often leads to death in early childhood.

Genetic

The GM2A gene is located on the long (q) arm of chromosome 5 at position 31.3-31.2, from base pair 129,886,686 to 129,896,112. The gene spans approximately 9.4 kilobases and consists of four exons. Various mutations in the GM2A gene, including missense mutations, nonsense mutations, and deletions, have been identified in individuals with GM2 gangliosidosis type AB.

Diagnosis

Diagnosis of GM2 gangliosidosis type AB involves a combination of clinical evaluation, biochemical testing, and genetic testing. Biochemical testing can detect reduced activity of beta-hexosaminidase A in leukocytes or fibroblasts. Genetic testing can identify mutations in the GM2A gene, confirming the diagnosis.

Treatment

There is currently no cure for GM2 gangliosidosis type AB. Treatment is supportive and symptomatic. Management may include physical therapy, nutritional support, and medications to manage seizures and other symptoms. Research into gene therapy and enzyme replacement therapy is ongoing and may offer hope for future treatments.

See Also

• Lysosomal storage disease
• Ganglioside
• Beta-hexosaminidase A