Gaucher disease

Abstract

Gaucher disease (GD) is the most common autosomal recessive lysosomal storage disease (LSD). It is caused by a mutation in the gene GBA1, which encodes enzyme acid p- glucosidase (glucocerebrosidase or glucosylceramidase E.C.3.2.1.45, GCase). A deficiency in GCase can lead to glucocerebroside (GLC) accumulation in the tissue macrophages. GD is classified into three subtypes: type 1 GD (GD1) is a chronic and non- neuronopathic phenotype accounting for 95% of GD cases; type 2 (GD2) and type 3 (GD3) cause nerve cell destruction or progressive neuroleptic deterioration. Currently, treatment of GD includes enzyme replacement therapies (ERTs) and substrate reduction therapies (SRTs). ERTs work by supplementing the defective enzyme GCase, while SRTs work by inhibiting the enzyme uridine diphosphate glucosylceramides synthase (UDP-GLC), which then inhibits the accumulation of GLC. Because the current ERTs or SRTs cannot cross the blood-brain barrier (BBB) of the central nervous system (CNS), these therapies cannot address the neurological problems seen in GD2 or GD3. This chapter summarizes classification, clinical manifestations, epidemiology, pathophysiology, diagnostic tools, available treatments options, and novel therapies.