Morbus Gaucher

Gaucher disease (GD) 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 . Types 2 and 3 are considered much rarer.

Clinical presentation

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
    • 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 ) , 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


Genetic changes

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 .


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

  • 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

Radiographic features

Plain radiograph

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 . Features of skeletal involvement include:

  • spleen
  • liver
    • hepatomegaly: less marked than the degree of splenomegaly
    • T2: hyperintense stellate areas representing inflammation and fibrosis
    • 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
    • may give a "salt and pepper pattern" due to scattered involvement
    • features of superimposed osteonecrosis
    • metaphyseal notching of humeri
    • pathological fractures
    • Erlenmeyer flask deformity

Treatment and prognosis

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

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


History and etymology

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

Siehe auch:
und weiter: