Gaucher Disease
Grace E. Kim, MD
Key Facts
Etiology/Pathogenesis
Accumulation of glucocerebroside in phagocytic cells
Autosomal recessive trait with mutation in acid β-glucosidase gene, GBA
Clinical Issues
Primarily involves liver, spleen, bone marrow, and bone
Results in hepatosplenomegaly, anemia, and thrombocytopenia
Microscopic Pathology
Accumulation of glucocerebroside in Kupffer cells and portal tract macrophages results in uniquely linear amphophilic cytoplasm
Sparing of hepatocytes
Ancillary Tests
Electron microscopy demonstrates intralysosomal compact long tubular structures
 H&E slide shows clusters of enlarged Kupffer cells  with uniquely striated cytoplasm in the lobule. |
 PAS-D positive aggregates of Kupffer cells with faintly fibrillary cytoplasm  fill the sinusoids. |
TERMINOLOGY
Synonyms
Glucocerebrosidase deficiency
Definitions
Inherited deficiency of the lysosomal enzyme glucocerebroside
ETIOLOGY/PATHOGENESIS
Inborn Error of Metabolism
Most common lysosomal glycolipid storage disorder
Enzyme deficiency
Acid β-glucosidase (glucocerebrosidase)
Accumulation of glucocerebroside (also called glucosylceramide) in phagocytic cells
Autosomal Recessive Disorder
Mutation in GBA, encoding acid β-glucosidase, on 1q21
c.1226A>G (N370S allele) is the most common mutant allele
