Genetic Heterogeneity of Gaucher Disease: Enzymatic and Immunologic Studies

  • Gregory A. Grabowski
  • Diane Fabbro
  • Tama Dinur
  • Karen Osiecki-Newman
  • Jack Goldblatt
  • Amy Feldman
  • Thomas Krulewski
  • Gunter Legler
  • Shimon Gatt
  • Robert J. Desnick
Part of the NATO ASI Series book series (NSSA, volume 116)


Gaucher disease (GD), the most prevalent lysosomal storage disease (1), is an autosomal recessive disorder of glycosphingolipid metabolism, resulting from the reduced activity of the lysosomal enzyme, acid ß-glucosidase [ß-Glc; N-acyl-sphingosyl-0-β-D-glucoside: glucohydrolase (EC] (2,3). The progressive accumulation of this enzyme’s major substrate, glucosyl ceramide (GC), within the lysosomes of the monocyte/macrophage system, leads to the diverse clinical manifestations of the disease (4,5). Three distinct phenotypes have been delineated based on the absence, or presence and severity of neuronopathic involvement (1). Type 1 GD (non-neuronopathic) is the most prevalent of the phenotypes and is characterized by remarkable variability in the age at clinical onset and degree of reticuloendothelial manifestations (6–8). Although occurring with highest frequency among Ashkenazi Jews (9), Type 1 GD has been described in patients from many different ethnic backgrounds (10–12). In contrast, Type 2 GD (acute neuronopathic) is a rare, panethnic, severe neurodegenerative disease which leads to death before two years of age (4). Type 3 GD, which occurs primarily in Sweden, is characterized by variable neuronopathic, visceral and boney involvement (13). Although originally described in Swedish individuals of Norrbottnian descent, other non-Swedish children with neuronopathic and severe reticuloendothelial manifestations have been classified as Type 3 GD (14,15). The Norrbottnian Type 3 GD patients presumably are homozygous for a single mutant allele at the ß-Glc structural gene locus, since all affected individuals were descended from a single couple who were married in the 1600s (13).


Residual Activity Phosphatidyl Serine Gauche Disease Lysosomal Storage Disease Gauche Disease Type 
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Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Gregory A. Grabowski
    • 1
  • Diane Fabbro
    • 1
  • Tama Dinur
    • 1
    • 4
  • Karen Osiecki-Newman
    • 1
  • Jack Goldblatt
    • 2
  • Amy Feldman
    • 1
  • Thomas Krulewski
    • 1
  • Gunter Legler
    • 3
  • Shimon Gatt
    • 4
  • Robert J. Desnick
    • 1
  1. 1.Division of Medical Genetics, Department of PediatricsMount Sinai School of MedicineNew YorkUSA
  2. 2.MRC Unit for Inherited Skeletal DysplasiasCapetownSouth Africa
  3. 3.lnstitut Fur BiochemieUniversitat KolnKolnGermany
  4. 4.Department of Membrane Biochemistry and NeurochemistryHebrew University-Hadassah Medical SchoolJerusalemIsrael

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