Gaucher disease is a rare genetic disorder that affects the body’s ability to break down and store fats. It is caused by a deficiency of an enzyme called glucocerebrosidase, which leads to the accumulation of a fatty substance called glucocerebroside in cells and tissues throughout the body. This can cause a wide range of symptoms, including an enlarged spleen and liver, anemia, low platelet count, and bone abnormalities. There are three main types of Gaucher disease, classified based on the severity of the symptoms: Type 1 (non-neuronopathic): This is the most common form of Gaucher disease and is typically characterized by mild to moderate symptoms. Type 2 (acute neuronopathic): This form of Gaucher disease is characterized by severe neurological symptoms and a rapid decline in neurological function. It is the most severe form of the disease and is often fatal in infancy. Type 3 (subacute neuronopathic): This form of Gaucher disease is intermediate in severity between Types 1 and 2. It is characterized by a slower decline in neurological function and a longer lifespan than Type 2.

The symptoms of Gaucher disease can vary depending on the type of the disease and the severity of the enzyme deficiency. In general, the symptoms of Gaucher disease may include: • An enlarged spleen and liver: These organs may become swollen due to the accumulation of fat cells. The spleen may also become damaged and may need to be removed. • Anemia: People with Gaucher disease may have low levels of red blood cells, which can cause fatigue and shortness of breath. • Low platelet count: Platelets are cells that help the blood clot, and a low platelet count can cause easy bruising and bleeding. • Bone abnormalities: People with Gaucher disease may have an increased risk of bone fractures, and may experience pain in the bones and joints. Type 1 (non-neuronopathic): mild to moderate symptoms. People with Type 1 Gaucher disease may have an enlarged spleen and liver, anemia, low platelet count, and bone abnormalities. They may also have a skin rash, yellowing of the skin (jaundice), and lung problems. Type 2 (acute neuronopathic): severe neurological symptoms and a rapid decline in neurological function. It is the most severe form of the disease and is often fatal in infancy. Symptoms may include seizures, exaggerated startle response, and a loss of muscle tone. Type 3 (subacute neuronopathic): intermediate in severity between Types 1 and 2. It is characterized by a slower decline in neurological function and a longer lifespan than Type 2. Symptoms may include delayed development, intellectual disability, and movement problems.

Gaucher disease is caused by mutations in the GBA gene, which provides instructions for making the glucocerebrosidase enzyme. These mutations can lead to a deficiency of the enzyme, resulting in the accumulation of fats in cells and tissues throughout the body.

Gaucher disease is typically diagnosed through a combination of laboratory tests and genetic testing. Some common tests used to diagnose Gaucher disease may include: • Enzyme assays: These tests measure the levels of glucocerebrosidase enzyme in the blood or other body fluids. A deficiency of this enzyme is a hallmark of Gaucher disease. • Genetic testing: This test involves analyzing a person’s DNA to look for mutations in the GBA gene, which is responsible for producing the glucocerebrosidase enzyme. • Imaging tests: These may include x-rays, CT scans, or MRI scans, which can help to visualize the organs and bones and look for any abnormalities that may be characteristic of Gaucher disease. • Other tests: Other tests, such as blood tests or bone marrow biopsies, may be used to look for other characteristics of Gaucher disease, such as anemia or low platelet count.

There is no cure for Gaucher disease, but there are several treatments available that can help to manage the symptoms and improve the quality of life for people with the condition. The specific treatment options for Gaucher disease may include: • Enzyme replacement therapy: This involves replacing the missing glucocerebrosidase enzyme with a synthetic version of the enzyme. • Substrate reduction therapy: This treatment works by reducing the production of the fatty substance (glucocerebroside) that accumulates in cells and tissues. • Bone marrow transplant: In some cases, a bone marrow transplant may be recommended, particularly those with severe bone abnormalities. • Splenectomy: An enlarged spleen may cause discomfort and may need to be removed. Following are the approved Enzyme Replacement Therapy for Gaucher Disease: • Cerezyme® (imiglucerase) by Sanofi Genzyme • VPRIV® (velaglucerase alfa) by Takeda • Elelyso® (taliglucerase alfa) by Pfizer Following are the approved Substrate Reduction Therapy available for Gaucher: • Cerdelga® (eliglustat) by Sanofi Genzyme • Zavesca® (miglustat) by Actelion