Gaucher Disease : General Disease Information

	The enzyme involved in Gaucher disease can be referred to in several different ways.  You may see acid β-glucosidase, glucocerebrosidase, or the abbreviation GCase. Likewise, the substrate that accumulates in Gaucher disease can be referred to as glucosylceramide, glucocerebroside, or the abbreviation GlcCer.  This website will use GCase and glucocerebroside to refer to the enzyme and substrate, respectively, involved with Gaucher disease.

Gaucher disease is an inherited lysosomal storage disorder caused by deficiency of an enzyme called β-glucocerebrosidase (GCase). The role of GCase within the body is to break down a complex fatty substance called glucocerebroside.  Reduced or absent levels of GCase activity leads to the accumulation of glucocerebroside in the affected tissues, including the spleen, liver, lungs, bone marrow, and sometimes in the brain. This accumulation of GCase is believed to cause the various symptoms of Gaucher disease, including an enlarged liver and spleen, skeletal disorders, and, in some instances, lung, kidney, and central nervous system impairment. Individuals with Gaucher disease may also bruise easily and experience pain and fatigue due to anemia and low blood platelets.

Historically, Gaucher disease has been described as a disorder caused by a missing enzyme. While some individuals do not make any enzyme, many individuals with Gaucher disease do make enzyme.   What’s Missing in Lysosomal Storage Diseases? (pdf - 6.5MB)     About Pharmacological Chaperones (pdf - 3.4MB)

It is estimated that Gaucher disease affects approximately 8,000 to 10,000 people worldwide. Gaucher disease is an autosomal recessive genetic disorder that affects both men and women. Most individuals with Gaucher disease have missense mutations in the GBA gene. Missense mutations can alter the structure of GCase, which results in the accumulation of the enzyme in a part of the cell called the endoplasmic reticulum (ER). As a result of the accumulation of GCase in the ER, the enzyme is unable to reach the lysosome, the part of the cell where GCase does its work.