Gaucher’s disease – Pathophysiology
- 02 Aug, 2018
- By UHAPO
Gaucher’s disease occurs due to deficiency of an enzyme called glucocerebrosidase (also known as acid beta-glucosidase, GBA). This enzyme acts on glucocerebroside, a part of cell membrane. The cause of decreased activity of this enzyme is a gene mutation on chromosome 1. Due to enzyme deficiency, lipids are accumulated in macrophages (large white blood cells that clear unwanted microscopic particles, such as bacteria and dead cells in the body). The macrophages get converted to Gaucher cells. The Gaucher cells infiltrate into various organs like bone marrow, spleen and liver. Three types ofGaucher’sdisease are known. The classification is based on age of onset, symptoms and whether there is neurological involvement. Gaucher disease type 1, (GD1), is characterized by splenomegaly (enlarged spleen), blood disorders, bone involvement and absence of neurological involvement. In Gaucher disease type 2 (GD2), there is hepatosplenomegaly (enlarged liver and spleen) along with neurological involvement within the first year of life. Nervous system involvement is seen right from childhood in Gaucher disease type 3 (GD3). Gaucher cells look like signet rings with crumpled tissue paper appearance. The cell nucleus is pushed to the periphery due to accumulation of lipids. There is direct toxic effect of bioactive lipids on nerve cells, causing cellular injury in the brain. There is neuronal loss and the neurons (nerve cells) look crumpled and shrunken in areas of brain like basal ganglia, midbrain, pons and medulla, cerebellum and hypothalamus. Gaucher cells are seen lying free within cerebral cortex. There is dysfunction of osteoblasts and osteoclasts (bone cells) leading to osteopenia (low bone mineral density due to bone loss). This can lead to bone pains and pathological fractures. In some cases, other organs like skin and lungs are also involved.