Gaucher disease

Gaucher disease (GD) is the most common lysosomal storage disease in humans ^4,5 and the most common genetic disease among Ashkenazi Jews ⁶.  It is a genetic multisystem disease arising from a deficiency of glucocerebrosidase activity, resulting in accumulation of a glycolipid (glucocerebroside) within the lysosomes of macrophages, particularity in the bone marrow, spleen and liver ^1,4-5.

Pathology

Classification

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

• type I (non-neuropathic form or adult form): commoner type ; progressive hepatosplenomegaly, anaemia and thrombocytopaenia, and marked skeletal involvement; lungs and kidneys may also be involved but the CNS is spared
• type II (acute neuropathic form or infantile form): severe progressive neurological involvement with death by 1 to 2 years of age; hepatosplenomegaly is also present (usually evident by 6 months of age)
• type III: type I with neurological involvement

Demographics and clinical presentation

Age of presentation depends on the type of Gauchers:

• type I:
  • 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), hepatosplenomegaly and haematological disturbances
• type II: evident by 6 months of age, with progressive neurological deterioration resulting in death by the age of 1 or 2
• type III: presents with mild neurological complications by late adolescence or early childhood ⁶

Radiographic features

Plain film

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:

• osteopenia
• osteonecrosis
• pathological / crush fractures
• endosteal scalloping
• Erlenmeyer flask deformities
• H shaped vertabrae 

MRI

• spleen
  • massive splenomegaly
  • splenic nodules (30%) ¹
  • splenic infarcts (33%)
• liver
  • hepatomegaly: less marked than the degree of splenomegaly
  • T2: hyperintense stellate areas representing inflammation and fibrosis ³
  • areas of hepatic ischaemia
• skeletal system
  • long bones are most severely affected
  • reduced T1 and T2 signal from involved bone marrow (due to infiltration with 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

Complications

• development of haemochromatosis
• avascular necrosis (AVN) of bone

Treatment and prognosis

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

Etymology

It is named after the French doctor Philippe Gaucher, who originally described it in 1882 ².