Gm1-gangliosidosis E75.1

Depending on the age of the disease, 3 types of GM1-Gangliosidose are distinguished:

• Type 1 GM1-Gangliosidosis, infantile form: severe, rapidly progressive form with onset before 6 months of age
• Type 2 GM1-Gangliosidosis, late-infantile or juvenile form with onset between 7 months and 3 years of age, with delayed motor and cognitive development
• Type 3 GM1-Gangliosidosis, adult, chronic form with late onset between 3 and 30 years of age and primarily generalized dystonia.

The severity of the disease seems to be related to the residual activity of beta-galactosidase.

Autosomal recessive mutations of the ß-galactosidase gene (gene locus: 3p21.33-3pter) that cause a defect in ß-galactosidase. More than 165 underlying mutations have been found so far. The enzyme defect leads to an increased toxic accumulation of GM-1 gangliosides, oligosaccharides and keratan sulfate mainly in the central nervous system (usually causing rapid decay) as well as in other organs.

Integument: appearance of angiokeratomas is possible. Clinical suspicion is based on signs of storage, such as coarsening of the face, gingival hyertrophy, cherry red macula, enlargement of internal organs, dysostosis and psychomotor retardation.

Typical symptoms are fatal cerebral degeneration, glycoside accumulation (GM1) in neurons, liver, spleen, or kidneys; also deformities of the skeleton.

Clinic; peripheral blood smear (vacuolized lymphocytes), analysis of oligosaccharides in urine. In bone marrow - Gaucher-like foam cells -. Determination of beta-galactosidase activity and/or DNA analysis.

Mucopolysaccharidoses, sphingolipidoses and oligosaccharidoses (see also lysosomal storage diseases)

The disease is usually fatal during the first 2 years of life.

Prenatal diagnosis in chorionic villi or amniotic cells is possible by determination of beta-galactosidase activity or, if familiality is known, by detection of the mutation.

1. Beck M (2001) Variable clinical presentation in lysosomal storage disorders. J Inherit Metab Dis 24: 47-51
2. Caffey JP (1951) Gargoylism (Hunter-Hurler disease, dysostosis multiplex, lipochondrodystrophy): prenatal and neonatal bone lesions and their early postnatal evolution. Bull Hosp Joint Dis 12: 38-66
3. Callahan JW (1999) Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal beta-galactosidase-like protein. Biochim Biophys Acta 1455: 85-103
4. Chen CS et al (1999) Broad screening test for sphingolipid-storage diseases. Lancet 354: 901-905
5. Chen CY et al (1998) Neuroimaging findings in late infantile GM1 gangliosidosis. AJNR Am J Neuroradiol 19: 1628-1630
6. Hanson M et al (2003) Association of dermal melanocytosis with lysosomal storage disease: clinical features and hypotheses regarding pathogenesis. Arch Dermatol 139: 916-920
7. Landing BH et al (1964) Familial neurovisceral lipidosis. An analysis of eight cases of a syndrome previously reported as Hurler-variant, pseudo-Hurler disease and Tay-Sachs disease with visceral involvement. Am J Dis Child 108: 503-522