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

[lamellar ichthyosis]

Sjögren-Larsson syndrome is a genetic disease characterized by ichthyosis , mental retardation , spasticity and mutations in the ALDH 3 A 2 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 .