Sjögren-Larsson syndrome

Molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency

Research output: Contribution to journalReview article

97 Citations (Scopus)

Abstract

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. Affected patients display ichthyosis, mental retardation and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients including amino acid substitutions, deletions, insertions and splicing errors. Most mutations are private, but several common mutations reflect founder effects, consanguinity or recurrent mutational events. FALDH oxidizes fatty aldehyde substrates arising from metabolism of fatty alcohols, leukotriene B4, ether glycerolipids and other potential sources such as sphingolipids. The pathogenesis of the cutaneous and neurologic symptoms is thought to result from abnormal lipid accumulation in the membranes of skin and brain; the formation of aldehyde Schiff base adducts with amine-containing lipids or proteins; or defective eicosanoid metabolism. Therapeutic approaches are being developed to target specific metabolic defects associated with FALDH deficiency or to correct the genetic defect by gene transfer.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMolecular Genetics and Metabolism
Volume90
Issue number1
DOIs
StatePublished - Jan 1 2007

Fingerprint

long-chain-aldehyde dehydrogenase
Sjogren-Larsson Syndrome
Molecular Biology
Metabolism
Mutation
Fatty Alcohols
Gene transfer
Lipids
Defects
Sphingolipids
Leukotriene B4
Schiff Bases
Eicosanoids
Neurocutaneous Syndromes
Founder Effect
Ichthyosis
Consanguinity
Aldehydes
Ether
Skin

Keywords

  • Fatty alcohol
  • Fatty aldehyde
  • Ichthyosis
  • Leukotriene
  • Mental retardation
  • Mutation
  • Spastic diplegia
  • ω-Oxidation

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Endocrinology, Diabetes and Metabolism

Cite this

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title = "Sj{\"o}gren-Larsson syndrome: Molecular genetics and biochemical pathogenesis of fatty aldehyde dehydrogenase deficiency",
abstract = "Sj{\"o}gren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. Affected patients display ichthyosis, mental retardation and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients including amino acid substitutions, deletions, insertions and splicing errors. Most mutations are private, but several common mutations reflect founder effects, consanguinity or recurrent mutational events. FALDH oxidizes fatty aldehyde substrates arising from metabolism of fatty alcohols, leukotriene B4, ether glycerolipids and other potential sources such as sphingolipids. The pathogenesis of the cutaneous and neurologic symptoms is thought to result from abnormal lipid accumulation in the membranes of skin and brain; the formation of aldehyde Schiff base adducts with amine-containing lipids or proteins; or defective eicosanoid metabolism. Therapeutic approaches are being developed to target specific metabolic defects associated with FALDH deficiency or to correct the genetic defect by gene transfer.",
keywords = "Fatty alcohol, Fatty aldehyde, Ichthyosis, Leukotriene, Mental retardation, Mutation, Spastic diplegia, ω-Oxidation",
author = "Rizzo, {William B}",
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AU - Rizzo, William B

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N2 - Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. Affected patients display ichthyosis, mental retardation and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients including amino acid substitutions, deletions, insertions and splicing errors. Most mutations are private, but several common mutations reflect founder effects, consanguinity or recurrent mutational events. FALDH oxidizes fatty aldehyde substrates arising from metabolism of fatty alcohols, leukotriene B4, ether glycerolipids and other potential sources such as sphingolipids. The pathogenesis of the cutaneous and neurologic symptoms is thought to result from abnormal lipid accumulation in the membranes of skin and brain; the formation of aldehyde Schiff base adducts with amine-containing lipids or proteins; or defective eicosanoid metabolism. Therapeutic approaches are being developed to target specific metabolic defects associated with FALDH deficiency or to correct the genetic defect by gene transfer.

AB - Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase (FALDH), an enzyme that catalyzes the oxidation of fatty aldehyde to fatty acid. Affected patients display ichthyosis, mental retardation and spastic diplegia. More than 70 mutations in ALDH3A2 have been discovered in SLS patients including amino acid substitutions, deletions, insertions and splicing errors. Most mutations are private, but several common mutations reflect founder effects, consanguinity or recurrent mutational events. FALDH oxidizes fatty aldehyde substrates arising from metabolism of fatty alcohols, leukotriene B4, ether glycerolipids and other potential sources such as sphingolipids. The pathogenesis of the cutaneous and neurologic symptoms is thought to result from abnormal lipid accumulation in the membranes of skin and brain; the formation of aldehyde Schiff base adducts with amine-containing lipids or proteins; or defective eicosanoid metabolism. Therapeutic approaches are being developed to target specific metabolic defects associated with FALDH deficiency or to correct the genetic defect by gene transfer.

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KW - ω-Oxidation

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