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Key Points

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  • Disease summary:

    • Gaucher disease is a lysosomal storage disease (LSD) which results from the deficient activity of the degradative enzyme, acid β-glucosidase, and the lysosomal accumulation of its glycosphingolipid substrate, glucosylceramide (GL-1), primarily in the monocyte-macrophage system.

    • Three major clinical subtypes of Gaucher disease have been described. Type 1 is the most common, and is differentiated from type 2 and type 3 by a lack of primary central nervous system involvement.

    • Type 1 Gaucher disease is most common in the Ashkenazi Jewish population (∼1 in 1000 affected; 1 in 15 is a carrier) and is characterized by hepatosplenomegaly, pancytopenia, and bone disease.

    • Type 2 Gaucher disease is characterized by onset in infancy and progressive psychomotor retardation with death by age 2. Individuals with type 3 diseases may have onset in infancy with a slowly progressive neurologic course and may survive into the third or fourth decade of life.

  • Hereditary basis:

    • Gaucher disease (all subtypes) is inherited as an autosomal recessive trait. Heterozygous carriers are asymptomatic, and when both parents are carriers there is a 25% risk for an affected child with each pregnancy.

  • Differential diagnosis (Table 87-1):

    • LSDs and mucopolysaccharidosis: Hepatosplenomegaly, which is seen in Gaucher disease, is present in other lysosomal storage diseases including types A and B Niemann-Pick disease and the mucopolysaccharidoses types I, II, III, VI, and VII. The presence of other clinical features as well as biochemical testing distinguishes these.

    • Saposin C deficiency: Patients with saposin C deficiency can present with symptoms similar to severe neuronopathic Gaucher disease. However, they have normal acid β-glucosidase activity.

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Table Graphic Jump Location
Table 87-1System Involvement
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Diagnostic Criteria and Clinical Characteristics

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Diagnostic Criteria

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Diagnosis is established by

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  • Determining the acid β-glucosidase enzyme activity in peripheral blood leucocytes is diagnostic for all subtypes. Affected individuals will have activity which is markedly decreased to less than 10% of normal mean activity. Enzyme activity does not differentiate the subtypes or predict disease severity.

  • Mutation analysis of the five most common mutations (N370S, L444P, 84GG, IVS2+1, and R496H) in the acid β-glucosidase gene will detect over 95% of mutations in Ashkenazi Jewish patients and around 50% to 60% in non-Jewish patients. DNA sequencing of the acid β-glucosidase gene will identify other mutations, and mutation analysis can predict disease subtype and prognosis.

  • Bone marrow examination ...

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