Journal of Inherited Metabolic Disease

, Volume 38, Issue 1, pp 65–76 | Cite as

Human genetic disorders of sphingolipid biosynthesis

  • Leonardo Astudillo
  • Frédérique Sabourdy
  • Nicole Therville
  • Heiko Bode
  • Bruno Ségui
  • Nathalie Andrieu-Abadie
  • Thorsten Hornemann
  • Thierry LevadeEmail author
Complex Lipids


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.


Ceramides Hereditary Spastic Paraplegia Sphingoid Base Ceramide Synthases GBA2 Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Autosomal recessive congenital ichthyosis










Hereditary sensory and autonomic neuropathy


Magnetic resonance imaging


Sphingosine 1-phosphate







This work was supported by INSERM, Université Paul Sabatier, ANR (SphingoDR program), RITC, LNCC (Equipe Labellisée 2013), CHU Toulouse, and the Vaincre les Maladies Lysosomales Foundation (for TL’s group), and the Gebert Rüf Foundation, the Center for Integrative Human Physiology (ZIHP, University of Zurich), “radiz” – Rare Disease Initiative Zurich, Clinical Research Priority Program for Rare Diseases, University of Zurich, and the European Commission (LSHM-CT-2006-037631) (for TH’s group).

Compliance with Ethics Guidelines

Conflict of Interest


Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


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© SSIEM 2014

Authors and Affiliations

  • Leonardo Astudillo
    • 1
    • 2
    • 3
  • Frédérique Sabourdy
    • 1
    • 2
    • 4
  • Nicole Therville
    • 1
    • 2
  • Heiko Bode
    • 5
  • Bruno Ségui
    • 1
    • 2
  • Nathalie Andrieu-Abadie
    • 1
    • 2
  • Thorsten Hornemann
    • 5
  • Thierry Levade
    • 1
    • 2
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    Email author
  1. 1.Centre de Recherches en Cancérologie de Toulouse (CRCT)Institut National de la Santé et de la Recherche Médicale (INSERM) UMR1037ToulouseFrance
  2. 2.Equipe Labellisée Ligue Nationale Contre le Cancer 2013, Centre de Recherches en Cancérologie de Toulouse (CRCT)Université de ToulouseToulouseFrance
  3. 3.Service de Médecine InterneCHU PurpanToulouseFrance
  4. 4.Laboratoire de Biochimie Métabolique, Institut Fédératif de BiologieCHU PurpanToulouseFrance
  5. 5.Institute for Clinical Chemistry, University Hospital Zurich and Center for Integrative Human PhysiologyUniversity of ZurichZurichSwitzerland

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