title: Ichthyosis in Sjögren-Larsson syndrome reflects defective barrier function due to abnormal lamellar body structure and secretion.
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.
authors.affiliation: Department of Pediatrics, University of Nebraska Medical Center, 985456 Nebraska Medical Center, Omaha, NE 68198-5456, USA. wrizzo@unmc.edu
authors.forename: William B
authors.initials: WB
authors.lastname: Rizzo
authors.forename: Dana
authors.initials: D
authors.lastname: S'Aulis
authors.forename: M Anitia
authors.initials: MA
authors.lastname: Jennings
authors.forename: Debra A
authors.initials: DA
authors.lastname: Crumrine
authors.forename: Mary L
authors.initials: ML
authors.lastname: Williams
authors.forename: Peter M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D000293:Adolescent; D000328:Adult; D000445:Aldehyde Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000235:genetics; D022081:Cell Surface Extensions / Q000473:pathology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004817:Epidermis / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017490:Ichthyosis, Lamellar; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics; D010084:Oxidation-Reduction; D055571:Secretory Pathway / Q000235:genetics; D016111:Sjogren-Larsson Syndrome / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
chemical_list: D000445:Aldehyde Oxidoreductases; C038828:long-chain-aldehyde dehydrogenase