g(m1)-ganglioside and Lactose-Intolerance

Topics: Aspartylglucosaminuria; Carbohydrate Metabolism, Inborn Errors; Chromatography, Paper; Fucose; G(M1) Ganglioside; Gangliosidoses; Glucosidases; Glycoproteins; Humans; Lactose Intolerance; Mannose; Mucolipidoses; Mucopolysaccharidoses; Neuraminidase; Oligosaccharides; Sandhoff Disease

Beta-galactosidase-deficient siblings in two litters of English springer spaniel puppies showed a progressive neurological impairment, dwarfism, orbital hypertelorism, and dysostosis multiplex. An excess of GM1-ganglioside was found in the brain. Three abnormal oligosaccharides were present in samples of urine, brain, liver, and cartilage. Light microscopy of selected tissue specimens revealed cytoplasmic vacuoles in neurons, circulating blood cells, macrophages, and chondrocytes. Ultrastructural studies demonstrated that these membrane-bound vacuoles were of two types--one containing lamellated membranes and the other, finely granular material. These clinical and pathological findings are similar to those observed in human patients affected by the infantile form of GM1-gangliosidosis.

Topics: Animals; Bone Diseases, Metabolic; Dog Diseases; Dogs; Female; G(M1) Ganglioside; Gangliosidoses; Humans; Lactose Intolerance; Male; Neurons; Oligosaccharides; Pedigree; Vacuoles

A patient with combined deficiency of sialidase and beta-galactosidase is described. This now 39-year-old man, who is of Japanese origin, showed gradually progressive clinical features from the age of six years. Many of these features are commonly found in sialidosis type 2 or in GM1-gangliosidosis. Both sialidase and beta-galactosidase activities were deficient in leucocytes and cultured fibroblasts. Leucocytes of his mother showed activities of both enzymes in the lower limit of the control range. Morphologically, the pattern of storage products in a skin biopsy resembled in many respects that seen in GM1-gangliosidosis. Moreover, storage products which could be typical of sialidosis were also observed. Since the patient showed angiokeratomata, the morphological findings were compared with those specific to Fabry's disease, but no similarities were found. An enzymological diagnosis of the disease is most reliable on cultured fibroblasts, discriminating it from sialidosis type 2 and GM1-gangliosidosis. In view of recent findings, leucocytes seem to be less suitable for the establishment of the diagnosis galactosialidosis.

Topics: Adult; Axons; Fibroblasts; G(M1) Ganglioside; Gangliosidoses; Humans; Lactose Intolerance; Leukocytes; Male; Neuraminidase; Skin; Vacuoles

Sphingolipid activator protein-1 (SAP-1) is a glycoprotein found in human tissue extracts that stimulates the enzymatic hydrolysis of at least two glycosphingolipids, including GM1 ganglioside and sulfatide. The ability of purified SAP-1 to stimulate GM1 ganglioside hydrolysis by extracts of cultured fibroblasts from patients with beta-galactosidase deficiency was examined, and all patients had a pronounced deficiency (under 10% of control). Using monospecific antibodies against SAP-1, the concentration was determined in cultured fibroblasts by rocket immunoelectrophoresis. Extracts from 15 control cell lines were found to have 0.72 +/- 0.24 micrograms cross-reactive material/mg protein, while cell extracts from 8 patients with GM1 gangliosidosis involving mental retardation were found to have 1.08 +/- 0.17, which is significantly elevated. When the fibroblast extracts were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by electroblotting, multiple bands were observed. Controls were found to have two major bands with estimated molecular weights of 9000 and 9500, and a minor band at 7800. Extracts from patients with GM1 gangliosidosis were found to have multiple bands ranging upward to 13,000. Extracts from patients with the most severe clinical types of GM1 gangliosidosis had almost exclusively high-molecular-weight forms (molecular weights above 10,000). Treatment of SAP-1 from control liver with endoglycosidase D caused a decrease in the Mr 9500 band and increased in the Mr 7800 band. When SAP-1 from GM1 gangliosidosis liver was treated sequentially with neuraminidase, beta-galactosidase, and endoglycosidase D, almost all of it was converted to the forms found in control human liver.

Topics: Cells, Cultured; Electrophoresis, Polyacrylamide Gel; Fibroblasts; G(M1) Ganglioside; Gangliosidoses; Glycoproteins; Humans; Hydrolysis; Immunoelectrophoresis; Lactose Intolerance; Metabolism, Inborn Errors; Molecular Weight; Proteins; Saposins; Sphingolipid Activator Proteins

Topics: Adult; beta-Galactosidase; Female; Fibroblasts; G(M1) Ganglioside; Gangliosides; Gangliosidoses; Humans; Infant; Lactose Intolerance; Placenta; Pregnancy; Reference Values

Urine samples from patients with different types of glycoprotein storage disease were chromatographed by gel filtration and the fractions analysed for sialic acid. Patients with mucolipidoses I and II excreted the largest amounts of bound sialic acid. One patient with GM1 gangliosidosis showed an abnormal level of sialyloligosaccharide excretion. Other patients showed normal results. With the present method mucolipidoses I and II, together with GM1 gangliosidosis, are readily distinguished from other possible oligosaccharidurias.

Topics: G(M1) Ganglioside; Gangliosidoses; Humans; Lactose Intolerance; Mucolipidoses; Mucopolysaccharidoses; N-Acetylneuraminic Acid; Neuraminidase; Oligosaccharides; Sialic Acids

An 11-year-old boy with type 2 GM1-gangliosidosis was presented, providing further evidence for the clinical and biochemical heterogeneity of the disease. The patient had several characteristics of type 2 GM1-gangliosidosis, but was different from so-called typical type 2 GM1-gangliosidosis from the point of view of survival and the degree of GM1-ganglioside accumulation. GM1-gangliosidosis was diagnosed by absence of beta-galactosidase activity in leukocytes and the parents had the enzyme levels of heterozygotes. However, the amount of the brain GM1-ganglioside was accumulated to a less degree in comparison with that of typical type 2 GM1-gangliosidosis, though the activity of GM1-beta-galactosidase in the brain was deficient to the same degree as in the typical case.

Topics: beta-Galactosidase; Child; G(M1) Ganglioside; Gangliosidoses; Humans; Lactose Intolerance; Leukocytes; Male; Prognosis

Kinetic studies of 4-methylumbelliferyl neuraminidase activity were carried out in cultured skin fibroblasts from patients with various disorders of neuraminidase deficiency. Cell extracts from two patients with dysmorphic type sialidosis of infantile onset, with isolated deficiency of neuraminidase activity, and three patients with dysmorphic type sialidosis of juvenile onset, with combined deficiency of neuraminidase and beta-galactosidase activities, demonstrated 7-12 times higher apparent Km values than those of normal controls (1.0-1.5 mmol/l as compared with 0.12-0.15 mmol/l). The apparent Ki values for N-acetylneuraminic acid and colominic acid were also increased in the dysmorphic type (7-15 and 7-11 times the normal values, respectively). In contrast, in the normomorphic type, normal apparent Km and Ki values were found for 4-methylumbelliferyl neuraminidase activity in fibroblasts from one patient with isolated neuraminidase deficiency and two patients with combined deficiency of neuraminidase and beta-galactosidase. The altered kinetics in the dysmorphic cases indicates a primary defect in neuraminidase with a secondary deficiency of beta-galactosidase in patients with combined deficiency. It is not clear if the primary defect in the normomorphic cases involves a defect in neuraminidase other than a Km defect or if neuraminidase or both neuraminidase and beta-galactosidase deficiencies are secondary to another defect as yet undetermined.

Topics: Cell Line; Fibroblasts; G(M1) Ganglioside; Gangliosidoses; Humans; Hymecromone; Kinetics; Lactose Intolerance; Mucolipidoses; Neuraminidase

Topics: Female; G(M1) Ganglioside; Gangliosidoses; Humans; Infant; Lactose Intolerance; Male; Microscopy, Electron; Pedigree; Skin; Tomography, X-Ray Computed

An infant with GM1 gangliosidosis was found to have an eruption at birth consisting of extensive and unusual slate blue macules resembling mongolian spots. All areas of skin were involved except face, scalp, palms, and soles. A biopsy of a macule obtained at 5 months of age demonstrated melanocytic cells in the dermis consistent with monogolian spot but also a perivascular histiocytic infiltrate. At 8 months of age, absence of beta-galactosidase activity was documented in both peripheral leukocytes and skin fibroblasts confirming the diagnosis of GM1 gangliosidosis. The dermal histiocytic cells noted on skin biopsy were interpreted as a manifestation of this storage disease. The coexistence of the hyperpigmented lesions and the heritable enzyme defect was believed to be coincidental.

Topics: beta-Galactosidase; G(M1) Ganglioside; Gangliosidoses; Humans; Infant; Lactose Intolerance; Nevus, Pigmented; Skin; Skin Neoplasms

A patient with chronic GM1 gangliosidosis was studied enzymatically and biochemically. Leukocyte acid beta-galactosidase activity was severely deficient. In brain and liver, the 4-methylumbelliferyl beta-galactosidase with acidic pH optimum and lactosylceramidase II were deficient while other hydrolases were present in normal amounts, including sialidase determined with N-acetylneuramin-lactose and fetuin as substrates. Neutral beta-galactosidase in liver was increased up to fourfold over the control. Corresponding to the pathological findings, GM1 ganglioside sialic acid was increased in the basal ganglia to 57% of the total (normal, 12 to 16%), accounting for the rise in total ganglioside to 180% of normal in this origin. Only slight to moderate elevations in the proportion of GM1 ganglioside were noted in the cerebral cortex and white matter, without major increase in total ganglioside. Elevated asialo GM1 ganglioside was also confined to the basal ganglia. There was no increase in hepatic glycoproteins or in keratan sulfate-like materials. This is the only known patient with chronic GM1 gangliosidosis in whom abnormal accumulation of GM1 ganglioside has been demonstrated in affected tissue and sialidase deficiency has been excluded as the primary genetic defect.

Topics: Adult; beta-Galactosidase; Brain Chemistry; Chronic Disease; G(M1) Ganglioside; Gangliosides; Gangliosidoses; Humans; Lactose Intolerance; Leukocytes; Liver; Lysosomes; Male

Topics: alpha-L-Fucosidase; Arabinose; beta-Galactosidase; Clinical Enzyme Tests; G(M1) Ganglioside; Gangliosidoses; Glycoside Hydrolases; Humans; Lactose Intolerance; Leukocytes

Available evidence indicates that a least two genetically distinct acidic lysosomal beta-galactosidases are present in mammalian tissues. One of them, galactosylceramidase, is primarily responsible for degradation of galactosylceramide, galactosylsphingosine, and monogalactosyl-diglyceride, while the other, GM1-ganglioside beta-galactosidase, degrades GM1-ganglioside and asialo GM1-ganglioside. Lactosylceramide can be hydrolyzed by either of the two enzymes. These substrate specificities of the two beta-galactosidases can adequately explain the known findings in the two genetic beta-galactosidase deficiency diseases. The possibilities of the specific lactosylceramidase have not yet received the necessary independent confirmation.

Topics: beta-Galactosidase; Brain; Ceramides; G(M1) Ganglioside; Galactosidases; Humans; Lactose Intolerance; Substrate Specificity

Topics: Acetylglucosaminidase; Arylsulfatases; beta-Galactosidase; Brain; Cerebrosides; Child, Preschool; Female; G(M1) Ganglioside; Glucuronidase; Hexosamines; Humans; Lactose Intolerance; Lipid Metabolism; Mucolipidoses; Mucopolysaccharidosis I; Organ Specificity; Sialic Acids; Sphingolipids

Topics: Alleles; G(M1) Ganglioside; Gangliosides; Gangliosidoses; Heterozygote; Homozygote; Humans; Lactose Intolerance; Lysosomes; Models, Biological; Mutation; Phenotype

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.

Topics: beta-Galactosidase; Consanguinity; Diagnosis, Differential; Female; Fibroblasts; G(M1) Ganglioside; Gangliosidoses; Genetic Complementation Test; Genotype; Humans; Infant, Newborn; Lactose Intolerance; Metabolism, Inborn Errors; Oligosaccharides; Phenotype; Sialic Acids

Topics: Brain; Child, Preschool; Diagnosis, Differential; Female; G(M1) Ganglioside; Gangliosides; Gangliosidoses; Humans; Infant; Lactose Intolerance; Liver; Male