g(m2)-ganglioside and Metabolism--Inborn-Errors

Topics: alpha-Galactosidase; Arylsulfatases; beta-Galactosidase; Cystine; Fabry Disease; G(M1) Ganglioside; G(M2) Ganglioside; Galactosylceramidase; Gangliosidoses; Genetic Carrier Screening; Glycoproteins; Heparitin Sulfate; Humans; Hydrolases; Isoelectric Focusing; Isoenzymes; Kinetics; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Lipid Metabolism, Inborn Errors; Lysosomes; Metabolism, Inborn Errors; Molecular Weight; Mucolipidoses; Niemann-Pick Diseases; Sphingolipidoses; Sphingomyelin Phosphodiesterase

Topics: Adolescent; beta-Galactosidase; Brain Diseases, Metabolic; Child; Child, Preschool; Clinical Enzyme Tests; Female; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosidoses; Humans; Infant; Infant, Newborn; Isoenzymes; Mass Screening; Metabolism, Inborn Errors; Models, Genetic; Phenotype; Pregnancy; Prenatal Diagnosis; Sandhoff Disease; Tay-Sachs Disease

Topics: Animals; Cats; Cattle; Disease Models, Animal; Dogs; G(M2) Ganglioside; Gangliosidoses; Gaucher Disease; Glycogen; Glycogen Storage Disease Type II; Glycopeptides; Humans; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Lipidoses; Lysosomes; Mannosidases; Metabolism, Inborn Errors; Mice; Niemann-Pick Diseases; Rabbits; Sphingolipids

Neurological dysfunction and structural cerebral abnormalities are commonly found in patients with methylmalonic and propionic acidemia. However, the mechanisms underlying the neuropathology of these disorders are poorly understood. We have previously demonstrated that methylmalonic and propionic acids induce a significant reduction of ganglioside N-acetylneuraminic acid in the brain of rats subjected to chronic administration of these metabolites. In the present study, we investigated the in vivo effects of chronic administration of methylmalonic (MMA) and propionic (PA) acids (from the 6th to the 28th day of life) on the distribution and composition of gangliosides in the cerebellum and cerebral cortex of rats. Control rats were treated with the same volumes of saline. It was first verified that MMA and PA treatment did not modify body, cerebellum, or cortical weight, nor the ganglioside concentration in the cerebral cortex of the animals. In contrast, a significant reduction in total ganglioside content in the cerebellum of approximately 20-30% and 50% of control levels occurred in rats injected with MMA and PA, respectively. Moreover, chronic MMA and PA administration did not interfere with the ganglioside pattern in the cerebral cortex, whereas the distribution of individual gangliosides was altered in the cerebellum of MMA- and PA-treated animals. Rats injected with MMA demonstrated a marked decrease in GM1 and GD3, whereas chronic PA treatment provoked a significant reduction of all ganglioside species, with the exception of an increase in GM2. Since gangliosides are closely related to the dendritic surface and other neural membranes, indirectly reflecting synaptogenesis, these ganglioside abnormalities may be associated with the brain damage found in methylmalonic and propionic acidemias.

Topics: Animals; Animals, Newborn; Body Weight; Central Nervous System; Cerebellum; Cerebral Cortex; Drug Administration Schedule; Female; G(M1) Ganglioside; G(M2) Ganglioside; Gangliosides; Metabolism, Inborn Errors; Methylmalonic Acid; Organ Size; Propionates; Rats; Rats, Wistar

Topics: alpha-Mannosidosis; Female; Fetal Diseases; G(M2) Ganglioside; Humans; Leukodystrophy, Metachromatic; Metabolism, Inborn Errors; Mucopolysaccharidoses; Pregnancy; Prenatal Diagnosis; Tay-Sachs Disease

Topics: G(M2) Ganglioside; Genetic Complementation Test; Hexosaminidases; Humans; Hybrid Cells; Hybridization, Genetic; Lipidoses; Metabolism, Inborn Errors