What are GM2 Gangliosidoses?

GM2 gangliosidoses are a group of diseases classified as “lysosomal storage diseases .”
Individuals with GM2 gangliosidoses are born with either a deficiency or reduced activity of the enzyme beta-hexosaminidase.
As a result, substances that should be broken down by this enzyme accumulate, leading to various symptoms throughout the body.

Types of GM2 Gangliosidoses

GM2 gangliosidoses are classified based on the affected gene and the age of onset.

1）Classification by Affected Gene:

GM2 gangliosidoses are divided into three subtypes based on the causative gene.

Disease Name

Affected Gene

Tay-Sachs Disease

HEXA

Sandhoff Disease

HEXB

GM2 Ganglioside Activator Protein Deficiency (AB Variant)
*Extremely rare

GM2A

2）Classification by Age of Onset:

GM2 gangliosidoses are also classified into infantile, juvenile, and adult forms based on the age of onset and enzyme activity levels.
The infantile form is the most common, while the juvenile and adult forms are less common.

Symptoms

Symptoms vary depending on the type of GM2 gangliosidoses (infantile, juvenile, or adult). Common symptoms of the infantile form include (illustrated below):

Diagnosis

If GM2 gangliosidoses are suspected, the diagnosis is confirmed through tests such as measuring enzyme activity in white blood cells and genetic testing.

Treatment

As of December 2025, there is no approved treatment for GM2 gangliosidoses.
Treatment focuses on managing symptoms, such as using anti-seizure medications for seizures and other therapies tailored to the patient's needs.

Prognosis

GM2 gangliosidoses are progressive diseases in which the symptoms described above gradually develop. The infantile form, in particular, is known for its rapid progression.

Editorial supervision: Norio Sakai, MD, PhD (Vice Head, Center for Promoting Treatment of Intractable Diseases, ISEIKAI International General Hospital)