Skip to Main Content

Gaucher disease and Niemann-Pick disease are the two lipid storage disorders that are most likely to be encountered by the hematologist because both may cause hepatosplenomegaly and cytopenias.

Gaucher disease is the most common autosomal recessive lipid storage disorder. It is most prevalent in Ashkenazi Jews, in whom the disease genotype occurs in approximately 1 in 850 births. Deficiency of the enzyme β-glucocerebrosidase results in accumulation of the glycolipid glucocerebroside in the cells of the macrophage-monocyte system. Patients with the common type 1 disease have no primary neuronopathic symptoms, but there is involvement of the central nervous system in type 2 and type 3 diseases. Diagnosis of Gaucher disease depends on demonstration of deficiency of β-glucocerebrosidase or identification of mutations in the β-glucocerebrosidase gene. Disease manifestations include hepatosplenomegaly, thrombocytopenia, anemia, osteoporosis with pathologic fractures and osteonecrosis, and, less commonly, pulmonary infiltration. Many patients, especially those who are homozygous for the common N370S (1226C→G) mutation, are protected against neurologic involvement, probably because of some residual glucocerebrosidase activity, and may manifest a mild disease that does not require specific therapy. There has been some concern about an increased incidence of malignancies and parkinsonism in patients with type 1 disease. For patients who have more severe signs and symptoms, effective enzyme replacement therapy with imiglucerase is available. The glucocerebroside substrate reduction therapy is also available but may cause adverse events.

Niemann-Pick disease is a heterogeneous group of autosomal recessive disorders. Type A and type B result from deficiency of the enzyme sphingomyelinase, whereas type C results from mutations in the NPC1 or NPC2 genes that appear to be involved in cholesterol trafficking, and results in accumulation of cholesterol as well as sphingomyelin. Type A is a severe lethal infantile form of the disease with marked progressive neurologic involvement. Type B is a later-onset form of the disease with no neurologic involvement but with hepatosplenomegaly in many patients. Patients with type C disease manifest neurologic signs and hepatosplenomegaly and may survive into adulthood. The marrow of these patients contains typical foam cells with small droplets in the cytoplasm and sea-blue histiocytes. Miglustat therapy was approved for patients with type C disease in 2008 in Europe.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: cDNA, complementary DNA; ERT, enzyme replacement therapy; HSGP, horizontal supranuclear gaze palsy; MRI, magnetic resonance imaging; SRT, substrate reduction therapy.

The glycolipid storage diseases are hereditary disorders in which one or more tissues become engorged with specific lipids, because of deficiencies of specific lysosomal enzymes required for hydrolysis of one of the glycosidic bonds. Figure 73–1 shows the catabolic pathway of glycosphingolipids and lists the diseases that are involved in impaired degradation because of specific enzyme deficiencies. The type of lipid and its tissue distribution have a characteristic pattern in each disorder. This chapter deals mainly with Gaucher disease, in which glucocerebroside is stored. It is the most ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.