Lipid Storage Diseases
Gaucher's Disease
a. 1882 - 1991: i. 1882: first described by Philippe Gaucher, "Gaucher's cell" in spleen at autopsy ii. 1900: defined as a familial disorder iii. 1920: neurological involvement characterized iv. 1965: enzyme deficiency identified as glucocerebrosidase v. 1984: glucocerebrosidase gene cloned vi. 1991: enzyme replacement therapy in clinical trials b. Deficiency of glucocerebrosidase which leads to an accumulation of glucocerebroside c. Gaucher's cells are macrophages seen in BM - look like creased tissue paper
Pseudo-Gaucher's Cells
a. Any disorder with high intramedullary turnover b. Seen in CML, thalessemia, AML, CLL, ITP, MA c. Gaucher-like histiocytes d. Cytoplasm looks like baby blue tissue paper
Mucopolysaccahridosis
a. Deficiency of enzymes involved in breakdown of mucopolysaccaharides b. Alder-Reilly bodies in WBCs, including lymphocytes and PMN; "Hurler's syndrome" , "Hunter's syndrome"
Tay-Sach's Disease
a. Deficiency of hexosaminidase A which leads to an accumulation of ganglioside GM2 b. Affecting neuron, eye c. Higher incidence in Ashkenazi Jews, death by 4 years old d. Vaculated lymphocytes and monos, helpful but not diagnostic
Niemann-Pick
a. Deficiency of sphingomyelinase which leads to an accumulation of sphingomyelin b. Niemann-Pick cells: large histiocytes (20-90 µ in diameter) with inconspicuous nucleus: Cytoplasm is filled with and distended by round uniformly sized and shaped lipid droplets c. Vaculated lymphs & monos
Lipid Storage Diseases
a. Rare genetic disorders - Abnormality in the catabolism of various glycolipids. gangliosides and globosides. As cells degrade, the lipids accumulate in organs (liver, spleen & BM) resulting in enlargement and/or dysfunction b. Lysosomal storage disease, subcellular accumulation of unmetabolized materials in the lysosome of various cells c. Usually present in hematology as problems related to hepatosplenomegaly - or with infection (lipid laden macrophages do poorly against infectious agents) d. Range from asymptomatic to severely debilitating and leading to early death e. Therapy is enzyme replacement, through prenatal detection - some cases need a BMT f. Lipid Storage Diseases: Gaucher's Disease, Niemann-Pick, Tay-Sachs, Sea-blue Histiocyte Syndrome, and Mucopolysaccharidosis
Sea-Blue Histiocytosis
a. Unknown enzyme deficiencies? that lead to the accumulation of ceroid (finely granular yellow brown pigment) b. Ceroid accumulates in macrophages of BM, liver and spleen c. Large histiocytes (50-60 µ in diameter) filled with colored granules that stain a tropical blue-green with Wright's stain
