General description

Infantile-onset GM1 gangliosidosis is a severe neurodegenerative lysosomal storage disorder caused by biallelic mutations in the GLB1 gene, leading to deficient activity of the enzyme β-galactosidase. This deficiency results in the accumulation of GM1 gangliosides, oligosaccharides, and keratan sulfate within lysosomes, precipitating widespread cellular dysfunction and apoptosis, particularly in the central nervous system (CNS). The disease is characterized by rapid neurological deterioration, systemic involvement, and a life expectancy rarely exceeding two to four years.

Infantile GM1 gangliosidosis usually presents within the first six months of life, beginning with symptoms like hypotonia, poor feeding, and exaggerated startle responses. Developmental regression typically starts around 3–4 months, marked by loss of motor skills and progressive cognitive decline. Coarse facial features—such as frontal bossing, gingival hypertrophy, and macroglossia—develop along with skeletal abnormalities like thoracolumbar kyphoscoliosis and anterior vertebral beaking. Around 50% of patients show macular cherry-red spots on eye exam. Systemic issues include visceromegaly, cardiomyopathy, and recurrent respiratory infections from aspiration. Most children die by age two, mainly due to respiratory or cardiac failure.

References

1. Erol, Ilknur, et al. "Neuroimaging findings in infantile GM1 gangliosidosis." European Journal of Paediatric Neurology 10.5-6 (2006): 245-248.