title: Human genetic disorders of sphingolipid biosynthesis.
abstract: Monogenic defects of sphingolipid biosynthesis have been recently identified in human patients. These enzyme deficiencies affect the synthesis of sphingolipid precursors, ceramides or complex glycosphingolipids. They are transmitted as autosomal recessive or dominant traits, and their resulting phenotypes often replicate the abnormalities seen in murine models deficient for the corresponding enzymes. In quite good agreement with the known critical roles of sphingolipids in cells from the nervous system and the epidermis, these genetic defects clinically manifest as neurological disorders, including paraplegia, epilepsy or peripheral neuropathies, or present with ichthyosis. The present review summarizes the genetic alterations, biochemical changes and clinical symptoms of this new group of inherited metabolic disorders. Hypotheses regarding the molecular pathophysiology and potential treatments of these diseases are also discussed.
authors.affiliation: Centre de Recherches en Cancérologie de Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037, Team n 4, CHU Rangueil, BP, 84225, 31432, Toulouse, France.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Astudillo
authors.forename: Frédérique
authors.initials: F
authors.lastname: Sabourdy
authors.forename: Nicole
authors.initials: N
authors.lastname: Therville
authors.forename: Heiko
authors.initials: H
authors.lastname: Bode
authors.forename: Bruno
authors.initials: B
authors.lastname: Ségui
authors.forename: Nathalie
authors.initials: N
authors.lastname: Andrieu-Abadie
authors.forename: Thorsten
authors.initials: T
authors.lastname: Hornemann
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
mesh_terms: D000818:Animals; D001259:Ataxia / Q000235:genetics; D004195:Disease Models, Animal; D004827:Epilepsy / Q000235:genetics; D006028:Glycosphingolipids / Q000096:biosynthesis*; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000235:genetics*; D051379:Mice; D009154:Mutation; D010264:Paraplegia / Q000235:genetics; D010523:Peripheral Nervous System Diseases / Q000235:genetics; D010641:Phenotype; D012173:Retinitis / Q000235:genetics; D013107:Sphingolipids / Q000096:biosynthesis*
chemical_list: D006028:Glycosphingolipids; D013107:Sphingolipids