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    Skin ultrastructural findings in type 2 Gaucher disease: diagnostic implications

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    Authors
    Chan, Aegean
    Holleran, Walter M.
    Ferguson, Tajh
    Crumrine, Debra
    Goker-Alpan, Ozlem
    Schiffmann, Raphael
    Tayebi, Nahid
    Ginns, Edward I.
    Elias, Peter M.
    Sidransky, Ellen
    UMass Chan Affiliations
    Lysosomal Disorders Treatment and Research Program
    Intellectual and Developmental Disabilities Research Center
    Document Type
    Journal Article
    Publication Date
    2011-12-01
    Keywords
    Adolescent
    Biopsy
    Child
    Child, Preschool
    Diagnosis, Differential
    Epidermis
    Female
    Gaucher Disease
    Genetic Association Studies
    Humans
    Infant
    Male
    Microscopy, Electron
    Middle Aged
    Mutation, Missense
    Pregnancy
    Prenatal Diagnosis
    Prognosis
    Young Adult
    Cellular and Molecular Physiology
    Congenital, Hereditary, and Neonatal Diseases and Abnormalities
    Molecular Genetics
    Nervous System Diseases
    Nutritional and Metabolic Diseases
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3224209/
    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. 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 site
    DOI
    10.1016/j.ymgme.2011.09.008
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34807
    PubMed ID
    21982627
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    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ymgme.2011.09.008
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