Chronic GM1 gangliosidosis presenting as dystonia: I. Clinical and pathological features

Area of Science:

• Neurology
• Pathology
• Biochemistry

Background:

• GM1 gangliosidosis is a rare lysosomal storage disorder.
• It is caused by a deficiency in the enzyme beta-galactosidase.
• This deficiency leads to the accumulation of GM1 ganglioside in various tissues, particularly the central nervous system.

Observation:

• A 27-year-old male patient presented with slowly progressive dystonia starting in early childhood.
• Clinical presentation included facial and limb involvement, leading to severe incapacitation with only mild intellectual decline.
• Notably absent were myoclonus, seizures, and macular cherry-red spots, distinguishing this case from typical presentations.

Findings:

• Postmortem examination revealed intraneuronal storage, predominantly in the basal ganglia, with characteristic multilamellated inclusions.
• Golgi studies identified meganeurites originating from medium spiny neurons.
• Vacuolated cells were observed in the reticuloendothelial system (Kupffer cells, histiocytes) and mild neuronal changes in the CNS.

Implications:

• This case expands the understanding of GM1 gangliosidosis clinical and pathological spectrum.
• It underscores the importance of biochemical confirmation (beta-galactosidase deficiency) in atypical neurological presentations.
• Further research into genotype-phenotype correlations in GM1 gangliosidosis is warranted.