Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinical description of an apparently classical case of type 1 GM1 gangliosidosis is presented. The patient was the first-born child of first cousins. She was diagnosed at 6 weeks and died at 6 months. beta-Galactosidase activity was deficient in cultured fibroblasts using [3H]GM1 ganglioside and [3H]ceramide-lactose as substrates. Genetic complementation studies performed after cell fusion between cultured fibroblasts from the patient and from two other type 1, one type 2, and one juvenile GM1 gangliosidosis strain were positive with all strains. Subsequent studies revealed an increased excretion of a sialic acid-containing hexasaccharide in the patient's cells. Parents' fibroblasts contained normal levels of beta-galactosidase. The case emphasizes the variability of the clinical expression in sialidosis and the importance of demonstrating a primary gene defect in establishing a diagnosis of an inborn error or metabolism.
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PMID:Infantile sialidosis: a phenocopy of type 1 GM1 gangliosidosis distinguished by genetic complementation and urinary oligosaccharides. 11

GM1 gangliosidosis is characterized by a deficiency in the lysosomal hydrolase beta-galactosidase, progressive nervous system disease and ocular lesions. Diagnosis of GM1 gangliosidosis in humans and cats with the analogous disease has been made by measurement of the enzyme activity in various tissues including brain, liver and cultured skin fibroblasts. The authors report the use of cultured conjunctival cells for this purpose derived from cats with feline GM1 gangliosidosis, a model of the human disease (juvenile GM1 gangliosidosis, Derry's disease). Full thickness conjunctival biopsies from three cats with GM1 gangliosidosis and two normal controls were used to initiate cell cultures. Optimal conditions for beta-galactosidase activity were established with an uncultured conjunctival biopsy from a normal cat. The fluorgen, 4-methylumbelliferyl-beta-D-galactopyranoside was used as substrate. After 2 months in culture, and 2 weeks after subculture, cells from cats affected with GM1 gangliosidosis exhibited specific activities for beta-galactosidase of 10, 9 and 12 nmoles 4MU/hr/mg protein, whereas specific activities for normals were 630 and 469 nmoles 4MU/hr/mg. Enzymatic analysis of cultured conjunctival cells may offer an effective alternative for the diagnosis of GM1 gangliosidosis.
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PMID:Diagnosis of feline GM1 gangliosidosis by enzyme assay of cultured conjunctival cells. 312 24

GM1 gangliosidosis is a genetic disease with lysosomal beta-galactosidase deficiency caused by mutations of the gene coding for this enzyme. However, apparently normal enzyme activity was found in plasma or serum from juvenile GM1 gangliosidosis patients homozygous for a mutation, R201C (201Arg-->Cys), after clotting for 30 min. This extracellular fluid finding is unusual in patients with primary and genetic deficiency of beta-galactosidase. The serum enzyme activity became relatively low only after 3 1/2-hour clotting because its increase in normal controls was not observed in these patients. beta-Galactosidase assay is not always reliable, particularly with serum or plasma as an enzyme source, for the diagnosis of hereditary beta-galactosidase deficiency, unless it is conducted under well-controlled conditions.
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PMID:Normal serum beta-galactosidase in juvenile GM1 gangliosidosis. 806 59

GM1 gangliosidosis and Morquio B syndrome, both arising from beta-galactosidase (GLB1) deficiency, are very rare lysosomal storage diseases with an incidence of about 1:100,000-1:200,000 live births worldwide. Here we report the beta-galactosidase gene (GLB1) mutation analysis of 21 unrelated GM1 gangliosidosis patients, and of 4 Morquio B patients, of whom two are brothers. Clinical features of the patients were collected and compared with those in literature. In silico analyses were performed by standard alignments tools and by an improved version of GLB1 three-dimensional models. The analysed cohort includes remarkable cases. One patient with GM1 gangliosidosis had a triple X syndrome. One patient with juvenile GM1 gangliosidosis was homozygous for a mutation previously identified in Morquio type B. A patient with infantile GM1 gangliosidosis carried a complex GLB1 allele harbouring two genetic variants leading to p.R68W and p.R109W amino acid changes, in trans with the known p.R148C mutation. Molecular analysis showed 27 mutations, 9 of which are new: 5 missense, 3 microdeletions and a nonsense mutation. We also identified four new genetic variants with a predicted polymorphic nature that was further investigated by in silico analyses. Three-dimensional structural analysis of GLB1 homology models including the new missense mutations and the p.R68W and p.R109W amino acid changes showed that all the amino acid replacements affected the resulting protein structures in different ways, from changes in polarity to folding alterations. Genetic and clinical associations led us to undertake a critical review of the classifications of late-onset GM1 gangliosidosis and Morquio B disease.
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PMID:GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings. 2149 94