i(3)so3-galactosylceramide and Metabolism--Inborn-Errors

Topics: Animals; Arylsulfatases; Brain; Ceramides; Cerebrosides; Female; Glycolipids; Humans; Kidney; Lipid Metabolism; Lipids; Male; Metabolism, Inborn Errors; Placenta; Pregnancy; Sphingolipids; Sulfatases; Sulfoglycosphingolipids; Sulfotransferases; Sulfuric Acids; Sulfurtransferases; Testis

Dysmyelination describes an inborn error of metabolism affecting myelinogenesis that causes it to be abnormal, arrested, or delayed. Abiotrophy or myelin as defined by Gowers, due to metabolic failure of the myelin maintenance system, is yet another feature of dysmyelination. In addition to the leukodystrophies, genetically determined conditions such as infantile amaurotic idiocy, hematosidosis, Niemann-Pick's disease and several of the aminoacidopathies are examples of dysmyelinating diseases. In order to reconcile morphological and neurochemical data in these conditions, it is necessary to reexamine a number of pathogenetic hypotheses based on known enzymatic deficiencies, and the interpretation of fragmentary biochemical analyses. The obligatory role of the neuron and axon in myelin formation and maintenance is reviewed. The hypothesis is advanced that gangliosides and their degradative products constitue precursors for the synthesis of the characteristic myelin sphingolipids cerebrosides, sulfatides, and sphingomyelin. Alterations in axoplasmic flow and of ganglioside metabolism must be condidered as important factors in the pathogenesis of dysmyelination.

Topics: Axons; Brain Diseases; Cerebrosides; Galactosidases; Gangliosides; Humans; Leukodystrophy, Globoid Cell; Leukodystrophy, Metachromatic; Lipidoses; Metabolism, Inborn Errors; Myelin Sheath; Sulfoglycosphingolipids

A patient with a new variant of multiple sulphatase deficiency (MSDv) is reported. Unlike the usual type, onset was late and progress was slow. The phenotypic changes were those usually seen in multiple sulphatase deficiency but much milder. Cytoplasmic accumulations were found in skin fibroblasts, and urinary mucopolysaccharides and sulphatides were high. Arylsulphatases A, B and C (ASA, B and C), heparan N-sulphatase sulphoiduronate sulphatase, and N-acetylgalactosamine 6-sulphatase all had low activity in lymphocytes and cultured skin fibroblasts. Complementation for ASA activity was found in hybrids between MSDv and metachromatic leukodystrophy (MLD) as well as between multiple sulphatase deficiency (MSD) and MLD. Complementation for ASC activity was also seen in hybrids between MSDv and X-linked ichthyosis (XLI), and between MSD and XLI. However, neither ASA nor ASC activity increased in hybrid cells of MSDv and MSD. These results suggested that the mutations of MSDv and of MSD were allelic, although of different phenotypes.

Topics: Adult; Alleles; Arylsulfatases; Female; Genetic Complementation Test; Glycosaminoglycans; Humans; Hybridization, Genetic; Leukodystrophy, Metachromatic; Metabolism, Inborn Errors; Mutation; Sulfatases; Sulfoglycosphingolipids

Topics: Acid Phosphatase; Cell Line; Cells, Cultured; Female; Fibroblasts; Fucose; Glycosaminoglycans; Glycoside Hydrolases; Hexosaminidases; Humans; Inclusion Bodies; L-Lactate Dehydrogenase; Malate Dehydrogenase; Male; Metabolism, Inborn Errors; Phenols; Sulfatases; Sulfoglycosphingolipids; Sulfur Radioisotopes

Topics: Anemia, Macrocytic; Atrophy; Autopsy; Blood Vessels; Brain; Brain Chemistry; Cerebrosides; Child; Cholesterol; Chromatography, Thin Layer; Demyelinating Diseases; Esters; Fatty Acids; Fatty Acids, Unsaturated; Female; Galactose; Gliosis; Globus Pallidus; Homocystinuria; Humans; Malonates; Metabolism, Inborn Errors; Phosphatidylcholines; Phospholipids; Sphingomyelins; Sulfoglycosphingolipids; Vitamin B 12

Topics: Adolescent; Adult; Brain; Cerebrosides; Diffuse Cerebral Sclerosis of Schilder; Female; Humans; Lipids; Male; Metabolism, Inborn Errors; Sulfates; Sulfoglycosphingolipids; Sulfur Isotopes