Gaucher disease is an autosomal recessive, lysosomal storage disorder, caused by a mutation in the acid β-glucosidase gene, located on chromosome 1q21. This results in the accumulation of the substrate glucosylceramide and other glycolipids due to a deficiency of beta-glucocerebrosidase. Gaucher disease is divided into three phenotypic forms:
- Type I disease (or nonneuropathic type) is most common. It involves bone disease, anemia, an enlarged spleen and thrombocytopenia. Type I affects both children and adults.
- Type II disease (or acute infantile neuropathic Gaucher disease) usually begins in infancy with severe neurologic involvement and is rapidly progressive leading to death by age 2-4 years
- Type III disease (chronic neuropathic form) may cause liver, spleen, and brain complications. Often more slowly progressive, patients may survive into the third or fourth decade.
High carrier frequency in individuals of Ashkenazi Jewish descent (1:16)
Major Phenotypic Features
- Bone lesions
- Hematologic changes
- Enlarged spleen (splenomegaly)
- Enlarged liver (hepatomegaly)
- Cognitive impairment
Enzyme replacement and substrate reduction therapies may be effective. Some patients may benefit from blood transfusion. Other patients may require joint replacement surgery to improve mobility and quality of life. Other treatment options include antibiotics for infections, anti-epileptics for seizures, bisphosphonates for bone lesions, bone marrow transplants, and liver transplants.