Gaucher Disease Molecular Basis of the Disease

Gaucher disease (GD) is another prevalent autosomal recessive lysosomal storage disorder that is found with higher incidence in the Ashkenazi Jewish population. The carrier frequency is 1 in 18 in this population and 1 in 100 in other populations12 (for comprehensive review on GD, see Reference 13). A defect in the enzyme glucocerebrosidase leads to the accumulation of glucocerebrosides in lysosomal compartments in macrophage/monocyte-derived cells, particularly in the liver, bone marrow, spleen, and lung. Several forms of GD exist. Type 1 GD has a wide range of clinical presentations, with some patients being asymptomatic, but can include bone disease, hepatosplenomegaly, anemia, and thrombocytopenia, but without primary central nervous system involvement. Types 2 and 3 have primary central nervous system involvement that varies by age of onset and rate of disease progression. Type 2 GD patients usually have an earlier age of onset than type 3 patients, with acute disease progression and death by approximately 2 years of age. Type 3 patients have onset in early childhood to adolescence and survive into their first to fourth decade of life. A perinatal-lethal form of GD also can occur, as well as a cardiovascular form characterized by aortic and mitral valve calcification, ophthalmologic abnormalities, and hydrocephalus.

The glucocerebrosidase gene (GBA) and its transcribed pseudogene (YGBA) are located on chromosome 1q21. Almost 200 mutations causing GD have been identified. Many of the mutations are most likely due to gene conversion events with the pseudogene.

0 0

Post a comment