Gaucher disease

Last revised by Henry Knipe on 10 Feb 2023

Gaucher disease is the most common lysosomal storage disorder in humans. It is an autosomal recessive, multisystem disease arising from a deficiency of glucocerebrosidase or beta-glucosidase activity, resulting in the accumulation of a glycolipid (glucocerebroside) within the lysosomes of macrophages, particularity in the bone marrow, spleen and liver.

Type 1 is the most common, affecting 1:500-1,000 Ashkenazi Jews and 1:50,000-100,000 of the general population 7. Types 2 and 3 are considered much rarer.

Age of presentation depends on the type of Gaucher disease:

  • type 1 (most common form)

    • age of presentation varies widely, with the mean age of diagnosis being 21 years of age 6

    • some patients present in childhood while others remain asymptomatic throughout life

    • clinical presentation tends to be with skeletal symptoms (bone pain, pathological fractures, osteonecrosis and bone crises ) 4, hepatomegaly, splenomegaly, and hematological disturbances

  • type 2: evident by 6 months of age, with progressive neurological deterioration resulting in death by the age of 1 or 2

  • type 3: presents with mild neurological complications by late adolescence or early childhood 6

Three types of Gaucher disease are described, each with different manifestations 1:

  • type 1 (non-neuropathic form or adult form): commoner type; progressive hepatomegalysplenomegaly, anemia and thrombocytopenia, and marked skeletal involvement; lungs and kidneys may also be involved, but the CNS is spared

  • type 2 (acute neuropathic form or infantile form): severe progressive neurological involvement with death by 1 to 2 years of age; hepatomegalysplenomegaly, is also present (usually evident by 6 months of age)

  • type 3: type 1 with neurological involvement

The glucosylceramide beta (GBA) gene provides instructions for making ß-glucocerebrosidase. Mutations in the GBA gene reduce or eliminate the function of this lysosomal enzyme leading to a build-up of toxic glucocerebroside and related substances in various tissues and organs 7.

Skeletal involvement is seen in 70-100% of patients and primarily involves long bones (tibia, humerus, femur) as well as vertebrae. Ribs, hands and wrists, ankles and feet, and mandible may also be involved 6. Features of skeletal involvement include:

  • spleen

  • liver

    • hepatomegaly: less marked than the degree of splenomegaly

    • T2: hyperintense stellate areas representing inflammation and fibrosis 3

    • areas of hepatic ischemia

  • skeletal system

    • long bones are most severely affected

    • reduced T1 and T2 signal from involved bone marrow (due to infiltration of Gaucher cells

    • bone marrow burden (BMB) score may be obtained from MRI images 4

    • may give a "salt and pepper pattern" due to scattered involvement

    • features of superimposed osteonecrosis

    • metaphyseal notching of humeri

    • pathological fractures

    • Erlenmeyer flask deformity

Enzyme replacement with macrophage-targeted glucocerebrosidase has been shown to be highly effective in type 1 Gaucher disease, halting the progression and even reversing both bone marrow and visceral infiltration 5. Radiographically, hepatomegaly and splenomegaly respond more rapidly than skeletal changes.

Glucosylceramide synthase inhibitors are available for patients with type 1 Gaucher disease who cannot receive enzyme replacement therapy 8.

First described by French physician Philippe CE Gaucher (1854-1918) in 1882, while still a medical student 2.

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Cases and figures

  • Case 1: splenomegaly
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  • Case 2: with bone infarcts in pelvis
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  • Case 3
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  • Case 4
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  • Case 5: splenic Gaucheroma
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