GM2-gangliosidosis, AB variant

autorecessive

GM2-gangliosidosis, AB variant is a rare lysosomal storage disorder that falls under the broader category of GM2 gangliosidosis. This genetic disorder is characterized by the accumulation of GM2 gangliosides in the neurons due to a deficiency in the GM2 activator protein, which is essential for the degradation of GM2 gangliosides by the enzyme beta-hexosaminidase A.

Pathophysiology

The GM2-gangliosidosis, AB variant, is caused by mutations in the GM2A gene located on chromosome 5q33.1. The GM2A gene encodes the GM2 activator protein, which is necessary for the proper function of beta-hexosaminidase A. In the absence of functional GM2 activator protein, GM2 gangliosides accumulate within the lysosomes of neurons, leading to progressive neurodegeneration.

Clinical Features

Patients with GM2-gangliosidosis, AB variant, typically present with symptoms in infancy or early childhood. Common clinical features include:

• Developmental delay
• Hypotonia
• Seizures
• Vision loss
• Hearing loss
• Spasticity
• Intellectual disability

Diagnosis

The diagnosis of GM2-gangliosidosis, AB variant, is based on clinical presentation, biochemical testing, and genetic analysis. Enzyme assays can demonstrate deficient activity of beta-hexosaminidase A in the presence of normal beta-hexosaminidase B activity. Genetic testing can confirm mutations in the GM2A gene.

Treatment

Currently, there is no cure for GM2-gangliosidosis, AB variant. Treatment is primarily supportive and focuses on managing symptoms and improving the quality of life. This may include:

• Anticonvulsants for seizure control
• Physical therapy to manage spasticity and maintain mobility
• Occupational therapy to assist with daily activities
• Speech therapy for communication difficulties

Prognosis

The prognosis for individuals with GM2-gangliosidosis, AB variant, is generally poor. The disease is progressive, and most affected individuals do not survive beyond early childhood.

Related Pages

• GM2 gangliosidosis
• Tay-Sachs disease
• Sandhoff disease
• Lysosomal storage disorder
• Beta-hexosaminidase
• Genetic disorder