Gaucher disease is a rare genetic disorder affecting individuals across all ages. It is recognized as a “storage disease” because it involves the abnormal buildup of certain fatty substances within the body’s cells and organs.
What Are Storage Diseases?
Storage diseases are genetic conditions where the body cannot properly break down specific molecules. Cells contain small compartments called lysosomes, often referred to as cellular recycling centers. Lysosomes house various enzymes designed to digest complex materials into simpler components. When one of these specialized enzymes is deficient or malfunctions due to a genetic change, the substances it normally processes begin to accumulate within the lysosomes. This unchecked buildup can lead to cellular dysfunction and tissue damage over time.
The Missing Piece in Gaucher Disease
Gaucher disease arises from a genetic alteration in the GBA1 gene. This gene provides instructions for producing an enzyme called glucocerebrosidase (GCase). Glucocerebrosidase normally functions within lysosomes to break down a fatty substance known as glucocerebroside. When the GBA1 gene is altered, the body produces insufficient amounts of functional glucocerebrosidase. This deficiency prevents the proper breakdown of glucocerebroside, causing it to remain within the lysosomes.
The Accumulation Process
Without adequate glucocerebrosidase, glucocerebroside accumulates within the lysosomes of specialized immune cells called macrophages. These macrophages, engorged with the undigested fatty substance, transform into characteristic “Gaucher cells.” Gaucher cells are often described as having a “crumpled tissue paper” appearance under a microscope. These enlarged Gaucher cells then collect in various organs. Their presence is most prominent in the spleen, liver, and bone marrow. In some forms of Gaucher disease, these cells can also accumulate in the lungs and brain, depending on the specific type of the condition.
How Storage Affects the Body
The accumulation of Gaucher cells in different organs leads to various symptoms. Buildup in the spleen and liver can cause these organs to become enlarged, resulting in a swollen abdomen and discomfort. This enlargement can also interfere with their normal functions. In the bone marrow, the presence of Gaucher cells can displace healthy cells, leading to anemia (low red blood cell counts) and thrombocytopenia (reduced platelets causing easy bruising and bleeding). Bone involvement can manifest as bone pain, bone crises, and an increased risk of fractures due to compromised bone strength. When accumulation impacts the brain, it can lead to neurological complications such as movement problems, seizures, and cognitive changes.