Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications
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Publisher version
UMass Chan Affiliations
Lysosomal Disorders Treatment and Research ProgramIntellectual and Developmental Disabilities Research Center
Document Type
Journal ArticlePublication Date
2011-12-01Keywords
AdolescentBiopsy
Child
Child, Preschool
Diagnosis, Differential
Epidermis
Female
Gaucher Disease
Genetic Association Studies
HumansInfantMaleMicroscopy, ElectronMiddle AgedMutation, MissensePregnancyPrenatal DiagnosisPrognosisYoung AdultCellular and Molecular PhysiologyCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMolecular GeneticsNervous System DiseasesNutritional and Metabolic Diseases
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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. beta-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. OBJECTIVES: To further assess the diagnostic utility of epidermal evaluations in distinguishing patients with type 2 Gaucher disease in an expanded cohort. STUDY DESIGN: 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. CONCLUSION: 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.Source
Chan A, Holleran WM, Ferguson T, Crumrine D, Goker-Alpan O, Schiffmann R, Tayebi N, Ginns EI, Elias PM, Sidransky E. Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications. Mol Genet Metab. 2011 Dec;104(4):631-6. doi: 10.1016/j.ymgme.2011.09.008. Epub 2011 Sep 16. PubMed PMID: 21982627; PubMed Central PMCID: PMC3224209. Link to article on publisher's siteDOI
10.1016/j.ymgme.2011.09.008Permanent Link to this Item
http://hdl.handle.net/20.500.14038/34807PubMed ID
21982627Related Resources
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