What is Gaucher Disease?

Gaucher disease is a rare metabolic disorder characterized by accumulation of lipids in organs and bones. The signs and symptoms can vary in severity and age of onset depending on the type of disorder, ranging from asymptomatic to severe, infancy to adulthood. Gaucher disease has been categorized clinically into three general types: Non-neuronopathic (central nervous system is typically not affected) 1. Type 1 Gaucher disease This is the most common form in individuals of Ashkenazi Jewish background. Typical symptoms include hepatosplenomegaly (enlarged liver and spleen), anemia (low red blood cell count), thrombocytopenia (bruising due to low number of platelets), osteopenia (decreased bone mass) and bone abnormalities. Neuronopathic (Central nervous system such as brain and spinal cord are affected) 2. Type 2 Gaucher disease This form is more severe. It has an early onset before the age of 2, and often causes life-threatening conditions at infancy. It is associated with the common symptoms observed in type 1 Gaucher disease, except bone disease is not observed. Other symptoms such as abnormal eye movement, seizure and damage to the brain are also observed in type 2 disease. 3. Type 3 Gaucher disease This form of the disease has a later age of onset and slower rate of progression than type 2. It is also associated with the common symptoms observed in type 1 Gaucher disease, in addition to symptoms such as abnormal eye movement, seizure and brain damage. Gaucher disease is caused by mutations in the GBA gene, which encodes the enzyme, beta-glucocerebrosidase. This enzyme functions in the lysosome to help break down lipids (glucocerebroside) into fragments (i.e. glucose and ceramide) for recycling. Mutations in the GBA gene prevent or reduce the function of beta-glucocerebrosidase. Individuals with a deficiency of this enzyme cannot break down glucocerebroside properly, resulting in accumulation of lipids in organs and tissues. Excessive levels of lipids can impair the functionality of the cells, leading to further damage and complications to the body. References: Hruska KS, LaMarca ME, Scott CR and Sidransky E (2008). Gaucher Disease: Mutation and Polymorphism Spectrum in the Glucocerebrosidase Gene (GBA). Human Mutation 29(5): 567-583. Jose CP, Ferreira MD, Schreiber-Agus N, Carter SM, Klugman S, MDa, Gregg AR, Gross SJ (2014). Carrier testing for Ashkenazi Jewish disorders in the prenatal setting: navigating the genetic maze. American Journal of Obstetrics and Gynecology. 211(3): 197-204. Pastores GM, Hughes DA (2000)