gangliosidosis

Gangliosidosis refers to a group of lysosomal storage disorders caused by deficiency of enzymes needed to degrade gangliosides, leading to accumulation of GM1 or GM2 gangliosides in cells, especially neurons. The condition is inherited in an autosomal recessive pattern and is classified into GM1 and GM2 types, with several subtypes under GM2.

GM1 gangliosidosis results from deficient beta-galactosidase (GLB1 gene). It has three clinical phenotypes: infantile, late-infantile/juvenile, and adult. Infants typically show hypotonia, developmental delay, hepatosplenomegaly, skeletal abnormalities, and coarse facial features, with rapid neurodegeneration. Later forms may present with ataxia, dysarthria, and movement disorders. Diagnosis is based on reduced beta-galactosidase activity in blood or fibroblasts and confirmatory GLB1 gene testing. Management is supportive and multidisciplinary, focusing on symptom control and quality of life.

GM2 gangliosidoses include Tay-Sachs disease (HEXA deficiency), Sandhoff disease (HEXB deficiency), and GM2 activator protein deficiency (GM2AP). Tay-Sachs is characterized by early neurodegeneration, exaggerated startle response, vision loss, and often a characteristic cherry-red macula; hepatosplenomegaly is typically absent. Sandhoff disease mirrors Tay-Sachs but commonly includes hepatosplenomegaly. GM2AP deficiency causes a variable GM2 accumulation. Diagnosis relies on deficient HEXA or HEXB enzyme activity and genetic testing for the respective genes. Imaging may reveal progressive neurodegeneration.

There is no widely available cure for gangliosidosis; care is primarily supportive and symptomatic. Some experimental approaches, including enzyme replacement or gene therapies, are under investigation. Prognosis varies by subtype and onset, with infantile forms generally associated with severe progression and early mortality, while later-onset forms may have slower progression. Carrier testing is advised in at-risk populations.