Lipid Storage Disorders : Biological and Medical Aspects

This book presents the proceedings of the meeting on "Lipid Storage Disorders" which took place in Toulouse, France, in September 14-18, 1987 and which was set up as a joint NATO Advanced Research Workshop and INSERM International Symposium. The meeting probably was the first truly international symposium devoted entirely to basic as well as applied aspects of lipid metabolism as related to the lipid storage disorders. Participants came from Europe, USA, Israel and Japan, and presented data on research in molecular biology and genetics, enzymology, cell biology as well as medical and epidemiological aspects of normal and pathological lipid metabolism. In the latter case, special attention was directed to the lysosomal B-glucosidase in relation to Gaucher disease and to sphin­ gomyelinase in relation to Niemann-Pick disease, and "two round" table discussions were devoted to the two respective items. But research on many other lipidoses was presented, as lectures or posters and avidly discussed. Other topics presented in special sessions were drug induced lipidoses and peroxisomal disorders. The meeting ended with a session devoted to medical aspects of disorders of lipid metabolism. The symposium which included about 50 lectures and close to 70 posters had an intense scientific character superimposed on a most pleasant and collegial atmosphere. Ample time was provided to personal discussions ; lodging of the participants in the students' residence located near the meeting place, permitted further contacts between them.

Lysosomal Storage Diseases.- Beta-glucosidases and Gaucher diseases.- The medical importance of the research on lipid storage diseases with a historical review on the advances in Gaucher disease.- The molecular biology of Gaucher disease.- Characterization of the normal human glucocerebrosidase genes and a mutated form in Gaucher’s patient.- Molecular biology of Gaucher disease: therapeutic strategies utilizing recombinant DNA technology.- Molecular properties of lysosomal glucocerebrosidase.- Comparison of human membrane-bound beta-glucosidases: lysosomal glucosylceramide-beta-glucosidase and non-specific beta-glucosidase.- Beta-glucocerebrosidase: mechanistic studies with covalent and non-covalent inhibitors.- Comparison of the acidic lipid requirement of control and type 1 Gaucher’s disease liver and brain glucocerebrosidases.- Heterogeneity in human acid beta-glucosidase with cellulose-acetate electrophoresis.- Etiology of a new identified Gaucher disease variant without glucosylceramidase defect.- Type 3 Gaucher disease : clinical and biological heterogeneity.- Parkinsonian symptomatology in a patient with type I (adult) Gaucher disease.- Sphingomyelinase and Niemann-Pick types A and B.- Acid sphingomyelinase from human urine: purification and characterisation.- Lysosomal sphingomyelinase: patients with Niemann-Pick disease have normal amounts of sphingomyelinase polypeptide.- Sphingomyelin storage in lymphoid cell lines from patients with Niemann-Pick disease types A, B and C: influence of culture conditions.- Turnover of docosahexaenoic acid in bis(monoacylglycero)phosphate induced in Niemann-Pick fibroblasts by incubation in presence of excess fatty acid.- Heterogeneity and special features of the storage process in Niemann-Pick disease.- Family with profound sphingomyelinase deficiency resisting closer subclassification.- Adult Niemann-Pick disease with psychiatric involvement.- Niemann-Pick disease types C and D.- Niemann-Pick disease type C: a lesion in intracellular cholesterol transport.- Pathophysiological approach of Niemann-Pick disease type C: definition of a biochemical heterogeneity and reevaluation of the lipid storage process.- Increase in sterol synthesis and decrease in cholesterol efflux in Niemann-Pick disease type C fibroblasts.- Abnormal cholesterol metabolism in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) murine mutant.- Studies on lysosomal storage diseases in cell culture: Niemann-Pick disease type D.- Beta-hexosaminidases and GM2-gangliosidoses.- Molecular genetics of beta-N-acetyl hexosaminidase alpha subunit mutations.- The molecular biology of beta-hexosaminidase: localization of the proteolytic processing and carbohydrate containing sites.- GM2-ganliosidosis: B1 variant with thermostable beta-hexosaminidase A and molecular analysis of the mutant enzyme.- Diagnosis of hexosaminidase A deficiency with sulphated substrate: evidence for an alpha-locus genetic compound in a Tay-Sachs variant.- Clinical and neurophysiological changes in carriers from a family with type O chronic GM2-gangliosidosis with ALS phenotype.- Other lysosomal enzymes and storage diseases.- Immunochemical studies of cerebroside sulphatase.- Correlation between degradation of sulfatide in cultured skin fibroblasts and residual arylsulfatase A activity.- Biochemical and ultrastructural studies of a fetus with arylsulfatase A deficiency.- Galactosylsphingosine in murine and human tissues of normal and globoid cell leukodystrophy cases.- Histoenzymological study of one case of Fabry disease before and after transplantation.- Alpha-L-fiicosidase: on the specificity of the two forms of normal human sera and their possible relationship to fucosidosis.- Molecular characterization of mutations causing fucosidosis in Italy.- Human placental sialidase: substrate specificity, molecular size and purification.- Metabolism of extracellular triacylglycerols (from lipoproteins) in a Wolman lymphoid cell line.- Activators and related pathologies.- The physiological roles of activator proteins for lysosomal glycolipid degradation.- Isoelectric focusing in immobilized pH gradients: a new approach for the study of the SAP-1 binding to lipids.- Studies on the defect in SAP-1 (sulfatide/GM1 activator)-deficient patients.- The role of a new glucosylceramidase activator protein in the binding of the enzyme to its natural substrate.- Splenic glucocerebrosidase and its cytosolic activator protein: effects on substrate hydrolysis and covalent inhibition by conduritol B epoxides.- Peroxisomes And Peroxisomal Disorders.- Peroxisomal disorders of lipid catabolism.- Genetic diseases affecting peroxisomal lipid biosynthesis.- Complementation analysis of peroxisomal diseases: kinetics of assembly of peroxisomes after fusion of complementary cell lines from patients deficient in peroxisomes.- Heterogeneity of beta-oxidation enzyme defects in peroxisomal diseases.- Beta-oxidation of omega-hydroxymonocarboxylic acids in rat liver peroxisomes and mitochondria.- Identification of the enzymic defect in X-linked adrenoleukodystrophy: oxidation of very long chain fatty acids is deficient due to an impaired ability of peroxisomes to activate very long chain fatty acids.- The metabolism of dicarboxylic acids in rat liver.- Mammalian metabolism of phytanic acid: recent findings.- Very long chain fatty acids and phytanic acid in genetic peroxisomal diseases.- Genetic peroxisomal disorders: GC-MS and SIM-GC-MS detection of pipecolic and phytanic acids.- Neonatal adrenoleukodystrophy. Ultrastructural variability in cultured skin fibroblasts from two skin biopsies of the same case.- Other Lipid Storage Disorders.- Use of 1-pyrenedecanoic acid for demonstrating the catabolic block of cytoplasmic triacylglycerols in a lymphoid cell line established from a patient affected with multisystemic lipid storage myopathy (type 3).- Alkane storage disease (very long chain N-alkanes): An original type of lipid storage of dietary origin from plant wax hydrocarbons.- Physical alterations of plasma lipoproteins in Tangier disease and their hypothetic involvement in pathogenesis.- Late infantile neuronal ceroid lipofuscinosis: abnormalities in the polyunsaturated fatty acid profiles of phospholipids in cultured skin fibroblasts.- Some characteristics of skin fibroblasts from ceroid-lipofuscinosis cultivated in vitro.- General Aspects Of Lipid Metabolism Related To Lipid Storage Disorders.- New methodologies.- Radiation fragmentation and inactivation of membrane proteins: interpretation of data for normal and muted oligomers.- Microscale synthesis of fluorescent cholesteryl esters for the study of lysosomal cholesteryl esterases and diagnosis of Wolman disease.- Determination of sphingomyelinase activity in cells and body fluids using a new fluorescent derivative of sphingomyelin; application to diagnosis of Niemann-Pick disease (application).- Determination of arylsulfatase A activity using pyrene derivatives of cerebroside sulfate.- Use of new fluorescent triacylglycerols for determining lipase activities and diagnosing Wolman disease.- Use of new fluorescent lipids for the study of the organization and dynamics of lipids in membranes.- Continuous spectrofluorometric measurements of the dispersion state and the uptake of pyrene dodecanoic acid by liposomes and cells.- One step purification of human pancreatic cholesterol ester hydrolase : application to the related enzyme of human milk.- Molecular and cellular biology and pathology.- Clinical diversity in lysosomal storage disorders: molecular and cellular aspects.- Gangliosides: uptake, intracellular transport and metabolism in normal and mutant cells.- Use of lipidotic cultured cells (from Wolman disease and multisystemic lipid storage myopathy) for studying the metabolic relations between the cellular compartments containing neutral lipids.- Administration of fluorescent derivatives of lipids into cultured cells and its use for detecting disorders of lipid metabolism.- Effect of albumin or serum on the uptake and degradation of pyrene cerebroside sulfate by lymphoblasts and skin fibroblasts.- Mitogenic effect of high density lipoprotein (HDL) on lymphoblastoid cells involved HMG-CoA reductase activity.- Metabolism of psychosine in SV40-transformed Schwann cell lines.- Psychosine and sphingosylphosphorylcholine bind to mitochondrial membranes and disrupt their function.- Beta-galactosidase and alpha-fucosidase of human fibroblasts show hardly binding to the mannose 6-phosphate receptor in comparison with beta-hexosaminidase.- In vivo uptake and metabolism of lactosylceramide on LDL in homozygotes with familial hypereholesterolemia.- Drug-induced models and animal models.- Effect of tricyclic antidepressants on lysosomal sphingomyelinase activity.- Castanospermine-induced deficiency of lysosomal beta-D-glucosidase: a model of Gaucher’s disease in fibroblasts.- The molecular basis of canine fucosidosis.- Alpha-mannosidase deficiency in persian cats: a model of human alpha-mannosidosis.- Sialidase deficiency in the SM/J mouse : a physically altered mutant enzyme in the liver.- Lipid metabolism and related enzymes.- Evolution of lysosomal proteins.- Lysosomal enzyme activity in rat brain during aging.- Purification and characterization of UDP-Gal: ceramide galactosyltransferase and reconstitution of its activity by incorporation into liposomes.- Stimulation of lipolytic enzymes in Alzheimer’s disease.- The de novo synthesis of choline in primary cultures of rat and chick neuron.- Effect of ethanol ingestion and pentazocine treatment on the forebrain gangliosides from rat.- Effect of fish oil feeding on rat heart lipids: composition and ultramicroscopic study.- Studies of phospholipase A2 activity and prostaglandin E2 levels in rat stomach following the ingestion of fish oil.- Influence of wheat bran and wheat germ on triglyceride and cholesterol absorption by the rat intestinal mucosa.- Glycoprotein alterations in lipid storage diseases.- Hyperlipoproteinemia in glycogen storage disease type I: effect of nocturnal intragastric feeding.- Diagnostic aspects and therapeutic trials.- Clinical heterogeneity of the lipidoses — A short overview.- Results of diagnosis and genetic counseling of sphingolipidoses in the GDR.- A new spot test for the screening of pathological urinary sulfated glycosaminoglycan excretion.- Differential approaches to therapy in lysosomal storage disorders.- Repeated implantations of human amniotic epithelial cells as a curative therapy of Niemann-Pick disease.- Neurological improvement following bone marrow transplantation in twitcher mice (murine globoid cell leukodystrophy).- Late submissions.- Gaucher Disease: enzymatic and molecular studies.- Clinical, biochemical, pathological “Zellweger-Like” disorder with morphologically normal peroxisomes.- Human alpha-galactosidase: characterization and TEukaryotic expression of the full-length cDNA and structural organization of the gene.- Participants.- Contributors.