Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion

William B. Rizzo, Dana S'Aulis, M. Anitia Jennings, Debra A. Crumrine, Mary L. Williams, Peter M. Elias

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Sjögren-Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjögren-Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal lamellar bodies, many with disrupted limiting membranes or lacking lamellar contents. Entombed lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of lamellar body secretion. At the stratum granulosum-stratum corneum interface, non-lamellar material displaced or replaced secreted lamellar membranes, and in the stratum corneum, the number of lamellar bilayers declined and lamellar membrane organization was disrupted by foci of lamellar/non-lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjögren-Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in lamellar body formation and secretion.

Original languageEnglish (US)
Pages (from-to)443-451
Number of pages9
JournalArchives of Dermatological Research
Volume302
Issue number6
DOIs
StatePublished - Aug 2010

Keywords

  • Aldehyde dehydrogenase
  • Fatty alcohol
  • Fatty aldehyde
  • Genetic disease
  • Ichthyosis
  • Stratum corneum

ASJC Scopus subject areas

  • Dermatology

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