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Type 3 (chronic) GM1 gangliosidosis presenting as infanto-choreo-athetotic dementia, without epilepsy, in three
G C Guazzi1, I D'Amore, F Van Hoof
1Istituto di Scienze Neurologiche, University of Siena, Italy.
Insights
This study details a rare case of severe dementia and neurological impairment in three sisters, linked to a combined beta-D-galactosidase and beta-D-fucosidase deficiency, a form of GM1 gangliosidosis.
Area of Science:
- Biochemistry
- Genetics
- Neurology
Background:
- GM1 gangliosidosis is a lysosomal storage disorder with significant clinical heterogeneity.
- Type 3 GM1 gangliosidosis typically presents with neurological and visceral symptoms.
Observation:
- Three sisters presented with infantile-onset dystonic dementia and spastic tetraparesis.
- Storage vacuoles were observed in CSF, bone marrow, and conjunctival cells.
- Biochemical analysis revealed increased urinary oligosaccharides and reduced acid beta-D-galactosidase and beta-D-fucosidase activity.
Findings:
- The patients exhibited a unique combination of beta-D-galactosidase and beta-D-fucosidase deficiencies.
- This enzymatic profile is associated with severe neurological manifestations, including dementia and motor deficits.
- Parents displayed heterozygous enzyme levels, indicating an autosomal recessive inheritance pattern.
Implications:
- This case highlights the broad clinical spectrum of GM1 gangliosidosis.
- The combined enzyme defect provides insight into the pathophysiology of this rare neurological disorder.
- Understanding this specific genotype-phenotype correlation is crucial for diagnosis and potential therapeutic strategies.
Abstract:
Three sisters (ages 27, 24, and 17 years) presented with slowly progressing dystonic dementia and spastic tetraparesis with infantile onset. CSF, bone marrow, and conjunctival cells showed storage vacuoles. Biochemical analysis revealed increased urinary oligosaccharide excretion and decreased activity of acid beta-D-galactosidase and beta-D-fucosidase in serum, leukocytes, and cultured fibroblasts. The parents' enzyme values were in the heterozygous range. This is the only case in the literature of severe dementia associated with the clinical symptoms of type 3 GM1 gangliosidosis. The clinical heterogeneity of GM1 gangliosidosis and the significance of the combination of beta-D-galactosidase and beta-D-fucosidase defects in this syndrome are discussed.