Morbus Gaucher

Metabolic and

storage lung diseases: spectrum of imaging appearances. A child with Gaucher disease. HRCT images shows fine linear opacities and hilar lymph node enlargement (arrowheads). Courtesy of Alan Brody, M.D. (Cincinnati, OH)

insightsimaging.springeropen.com • Open Access

Splenomegaly

• Gaucher disease - massive splenomegaly - Ganzer Fall bei Radiopaedia

Sargent, M. Gaucher disease - massive splenomegaly. Case study, Radiopaedia.org. (accessed on 20 Oct 2022) https://doi.org/10.53347/rID-6002 • CC by-nc-sa 3.0 (modified)

Gaucher

disease • Bone infarcts in Gaucher disease - Ganzer Fall bei Radiopaedia

Dawes L, Bone infarcts in Gaucher disease. Case study, Radiopaedia.org (Accessed on 03 Dec 2022) https://doi.org/10.53347/rID-35884 • CC by-nc-sa 3.0 (modified)

Erlenmeyer

flask deformity • Gaucher disease - Ganzer Fall bei Radiopaedia

Radswiki T, Gaucher disease. Case study, Radiopaedia.org (Accessed on 01 Dec 2022) https://doi.org/10.53347/rID-11451 • CC by-nc-sa 3.0 (modified)

Gaucher

disease • Gaucher disease - adult - Ganzer Fall bei Radiopaedia

Robertson P, Gaucher disease - adult. Case study, Radiopaedia.org (Accessed on 03 Dec 2022) https://doi.org/10.53347/rID-21944 • CC by-nc-sa 3.0 (modified)

Gaucher

disease • Gaucher's disease - splenic Gaucheroma - Ganzer Fall bei Radiopaedia

Silverstone L, Gaucher's disease - splenic Gaucheroma. Case study, Radiopaedia.org (Accessed on 03 Dec 2022) https://doi.org/10.53347/rID-92112 • CC by-nc-sa 3.0 (modified)

Radiopaedia • CC-by-nc-sa 3.0 • de

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.

Epidemiology

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

Pathology

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 .

Classification

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

type 1 (non-neuropathic form or adult form): commoner type; progressive hepatomegaly, splenomegaly, 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; hepatomegaly, splenomegaly, 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:

osteopenia
osteonecrosis
pathological/crush fractures
endosteal scalloping
Erlenmeyer flask deformities
H-shaped vertebrae
paranasal sinus obliteration due to medullary expansion

MRI

spleen
- massive splenomegaly
- splenic nodules (30%)
- splenic infarcts (33%)
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 .

Complications

o steonecrosis of the hip
pathological fracture and pyogenic osteomyelitis
lung involvement
- pulmonary infiltration by Gaucher cells (type 2)
- parenchymal infiltration with fibrosis (type 3)
- pulmonary hypertension
increased frequency of multiple myeloma, Parkinson disease and Lewy body dementia
Gaucheromas: rare pseudotumors comprising a mass of Gaucher cells