Understanding Gaucher Disease

Gaucher disease (pronounced go-SHAY) is caused by a defect in the GBA gene. The faulty GBA gene results in a deficiency of an essential lysosomal enzyme called glucocerebrosidase (GCase), which functions to break down a fatty substance called glucocerebroside (GluCer).1  When the enzyme is deficient or does not function properly, lipid-laden lysosomes of macrophages (cells of the immune system) become engorged with glucocerebroside leading to the progressive signs and symptoms of Gaucher disease.

There are three types of Gaucher disease with type 1 being the most common.

Type 1 Gaucher disease: clinical signs and symptoms include an enlarged spleen and liver (hepatosplenomegaly), extreme fatigue due to a low number of red blood cells (anemia), easy bruising and bleeding (e.g., nosebleeds) due to a low number of platelets (thrombocytopenia) and significant bone complications including: reduced bone density and strength (osteopenia/osteoporosis), fractures, bone death (avascular necrosis), and severe bone pain/bone crisis. Growth delay is often present in children.2 Rarely type 1 Gaucher disease can affect the lungs, eyes and kidneys of patients.3 Due to the vague and common clinical symptoms, patients are often misdiagnosed.

Type 2 and 3 Gaucher disease have primary neurologic manifestations affecting the brain and central nervous system (CNS), also called neuronopathic.

Type 2 Gaucher disease is an acute neuronopathic form of Gaucher disease that presents in the first year of life.  There is a poor clinical prognosis associated with type 2 disease.4

Type 3 Gaucher disease is a chronic neuronopathic form of the disease that may initially be hard to distinguish from type 2. Individuals with type 3 Gaucher disease typically have a slower progressive disease course. Symptoms can mirror those of type 1 and type 2 disease with patients surviving into adulthood. 4

How is Gaucher Disease Inherited?

Gaucher disease is inherited in an autosomal recessive manner. Normally, a person has two working copies of the gene that provides the instruction code for making the glucocerebrosidase enzyme. When a person has one normal gene and one faulty gene they are called a “carrier” and do not develop Gaucher disease. When two carrier parents have children, each parent will pass one of their genes (either the normal gene or the faulty gene) to their child. With each pregnancy, two carrier parents have a 25% chance of having an unaffected child, a 1 in 2 (50%) chance of having a carrier child, and a 1 in 4 chance (25%) of having a child affected by Gaucher disease.4  Males and females are equally affected.

How Common is Gaucher Disease?

Type 1 Gaucher disease is one of the most common lysosomal disorders and affects approximately 1:40,000- 60,000 people in the general population. Type 1 Gaucher disease is also the most common Jewish genetic disease affecting ~1:855 of Ashkenazi ancestry.4

1 Futerman AH, Platt FM. The metabolism of glucocerebrosides - From 1965 to the present.
Mol Genet Metab. Volume 120, Issues 1-2:22-26 (2017).

2 Kaplan P et al. The clinical and demographic characteristics of nonneuronopathic Gaucher disease in 887 children at diagnosis.
Arch Pediatr Adolesc Med.160(6):603-8 (2006). 

3 Mistry PK et al. Understanding the natural history of Gaucher disease.
American Journal of Hematology. Volume 90, Issue Supplement S1:S6–S11 (2015).

4 Pastores GM et al. Gaucher Disease.
GeneReviews Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle; (2015).