1. MLAB 1315-Hematology Keri Brophy-Martinez Unit 26: Lipid Storage Diseases

2. LIPID (LYSOSOMAL)STORAGE DISEASES AND HISTIOCYTES These are autosomally inherited disorders known as lysosomal storage diseases because there is an accumulation of unmetabolized material in the lysosomes of various cells. They are caused by various enzyme defects (inborn errors) in lipid metabolism linked to an enzyme deficiency.

3. There are three main disorders: Gaucher’s Disease Enzyme deficiency: β-glucocerebrosidase Causes an accumulation of glucocerebroside in predominantly the monocyte-macrophage system Gaucher’s cell: large histiocyte (20-100Fm) with displace nucleus which contains one or more round nucleoli. Cytoplasm is faintly blue/white with characteristic “crumpled tissue paper” appearance which is probably the result of glycolipid deposition.

4. Gaucher’s Disease Prevalent in the Ashkenazi Jewish population (eastern European) Adult form (Type I) - most common; mild form Infantile form (Type II) - rare; death occurs by age 2 (failure to thrive); neurological involvement Juvenile form (Type III) - clinical and physical findings range between Type I and Type II

5. Gaucher’s Disease Treatment Enzyme replacement therapy approved in 1991 in U.S. Bone marrow transplant Supportive therapy (splenectomy)

6. Niemann-Pick Disease Enzyme deficiency: sphingomyelinase Causes an accumulation of unmetabolized sphingomyelin and cholesterol Niemann-Pick cell: lipid-laden giant foamy cell found in BM, tissues and other organs

7. Niemann-Pick Disease Increased incidence in the Jewish population Five types have been described Classic form presents with jaundice at birth, hepatosplenomegaly, enlarged lymph nodes, neurological symptoms, retarded physical and mental development. Death occurs by age 2.

8. Niemann-Pick Disease Treatment No current treatment is available for Type A. Type B has been successfully treated with bone marrow transplant.

9. Tay Sachs Disease Enzyme deficiency: hexosaminidase A Foamy lymphocytes are present but are not diagnostic.

10. Tay Sachs Disease Higher incidence in Ashkenazi Jewish population Severity of the disease correlates with residual enzyme activity. The buildup of unmetabolized GM2 ganglioside in the tissues has devastating effects in the central nervous system and eye. Physical and mental deterioration occur along with seizures and paralysis. Death comes by age 4.