Sjogren-Larsson syndrome

William B Rizzo MD (Dr. Rizzo of the University of Nebraska Medical Center and the Children's Hospital of Omaha has no relevant financial relationships to disclose.)
Raphael Schiffmann MD, editor. (Dr. Schiffmann, Director of the Institute of Metabolic Disease at Baylor Research Institute, received research grants from Amicus Therapeutics, Protalix Biotherapeutics, and Shire.)
Originally released October 22, 1996; last updated April 11, 2016; expires April 11, 2019

This article includes discussion of Sjogren-Larsson syndrome, ALDH3A2 deficiency, fatty alcohol:NAD+ oxidoreductase deficiency, fatty aldehyde dehydrogenase deficiency, ichthyosis, spastic neurologic disorder, and oligophrenia, Sjögren-Larsson syndrome, and SLS. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Sjögren-Larsson syndrome is an inherited neurocutaneous disorder characterized by ichthyosis, intellectual disability, and spastic diplegia or tetraplegia. Patients have deficient activity of fatty aldehyde dehydrogenase due to mutations in the ALDH3A2 gene, which results in altered lipid composition of their tissues. In this article, the author discusses new information about the biochemical pathogenesis of Sjögren-Larsson syndrome.

Key points

 

• Consider the diagnosis of Sjögren-Larsson syndrome in any patient with intellectual disability, spasticity, and dry skin or ichthyosis.

 

• Brain MRI typically shows white matter disease, and ophthalmologic exam often reveals a distinctive crystalline maculopathy.

 

• Diagnostic testing demonstrates deficiency of fatty aldehyde dehydrogenase activity in cultured skin fibroblasts or mutations in the ALDH3A2 gene.

 

• Sjögren-Larsson syndrome typically is not a progressive neurodegenerative disease, and patients survive well into adulthood.

Historical note and terminology

Sjögren and Larsson first described the genetic syndrome that bears their names in a cohort of 28 Swedish patients (Sjögren and Larsson 1957). Richards (Richards 1972) and Theile (Theile 1974) reviewed subsequent cases of Sjögren-Larsson syndrome that added considerably to the clinical description of patients and highlighted the worldwide distribution of this disease. In a series of papers published in the 1980s, Jagell and colleagues provided extensive descriptions of the phenotype in the Swedish patients, including estimates of the prevalence of the disease in Sweden. Sjögren-Larsson syndrome was transformed from a purely clinical disorder to an inborn error of metabolism by the finding that patients have impaired fatty alcohol oxidation due to deficient activity of fatty alcohol:NAD+ oxidoreductase (Rizzo et al 1988). Subsequent investigations demonstrated that the primary enzymatic defect in Sjögren-Larsson syndrome is deficient activity of the fatty aldehyde dehydrogenase component of fatty alcohol:NAD+ oxidoreductase (Rizzo and Craft 1991). Enzymatic studies have permitted the identification of genetic carriers for Sjögren-Larsson syndrome (Kelson et al 1992) and prenatal diagnosis (Rizzo et al 1994). The gene for fatty aldehyde dehydrogenase has been cloned, and patients with Sjögren-Larsson syndrome were found to carry mutations of various types (De Laurenzi et al 1996).

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