title: Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications.
abstract: BACKGROUND
  Type 2 Gaucher disease is a rare and progressive subtype of this lysosomal storage disorder, marked by rapid, early-onset neurodegeneration. Distinguishing type 2 from types 1 and 3 Gaucher disease has remained challenging, due to the lack of a clear correlation between phenotype and enzymatic activity or genotype. β-glucocerebrosidase, the enzyme deficient in Gaucher disease, also has an essential role in maintaining epidermal permeability function, by regulating the ratio of ceramides to glucosylceramides in the stratum corneum of the skin.
  
  
  OBJECTIVE
  To further assess the diagnostic utility of epidermal evaluations in distinguishing patients with type 2 Gaucher disease in an expanded cohort.
  
  
  METHODS
  Epidermal samples were evaluated from twenty children with type 2, three patients with type 3 Gaucher disease and two adults with type 1 Gaucher disease with different clinical manifestations and genotypes. Electron microscopy on ruthenium tetroxide post-fixed tissue was performed.
  
  
  RESULTS
  Compared to controls and subjects with type 1 and type 3 Gaucher disease, only patients with type 2 Gaucher disease displayed characteristic electron dense, non-lamellar clefts and immature-lamellar membranes.
  
  
  CONCLUSIONS
  The appearance of characteristic alterations in epidermal ultrastructure provides an early and specific diagnostic tool to help in distinguishing type 2 from the other types of Gaucher disease.
authors: Department of Dermatology, VA Medical Center & University of California, San Francisco, CA, USA.
authors: Aegean
authors: A
authors: Chan
authors: Walter M
authors: WM
authors: Holleran
authors: Tajh
authors: T
authors: Ferguson
authors: Debra
authors: D
authors: Crumrine
authors: Ozlem
authors: O
authors: Goker-Alpan
authors: Raphael
authors: R
authors: Schiffmann
authors: Nahid
authors: N
authors: Tayebi
authors: Edward I
authors: EI
authors: Ginns
authors: Peter M
authors: PM
authors: Elias
authors: Ellen
authors: E
authors: Sidransky
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D004817:Epidermis / Q000473:pathology*; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008854:Microscopy, Electron; D008875:Middle Aged; D020125:Mutation, Missense; D011247:Pregnancy; D011296:Prenatal Diagnosis; D011379:Prognosis; D055815:Young Adult