Taking Charge of Your Health

Gaucher disease is an inherited condition
characterized by insufficient levels of the enzyme glucocerebrosidase, also called beta-glucosidase.
It’s named for the French physician, Philippe Gaucher, who first described the condition. Glucocerebroside is a glycolipid, which is
a molecule containing both sugar and fat, that’s included in the membrane of many different
cells. Glucocerebroside is formed through a set of reactions in the cell that require
enzymes. Once the glucocerebroside is made it becomes a part of various cells and when
these cells become old or damaged, they are often engulfed, or eaten, by immune cells
called macrophages. Macrophages contain lysosomes, which are organelles that act as the cells’
digestive center. Inside lysosomes, large, potentially harmful substances are broken
down, to be either discharged or reused by the body. One example is glucocerebroside
which is broken down by the enzyme glucocerebrosidase, or GBA, which is a product of the GBA gene. In Gaucher disease, the GBA gene is faulty,
meaning it has a mutation that leads to a reduction in the level or activity of glucocerebrosidase.
Hence, glucocerebroside can’t be broken down and it accumulates inside the lysosomes
of macrophages. So under a microscope, macrophages have a characteristic lipid-laden, or “fatty”
appearance, similar to “crumpled tissue-paper.” These transformed macrophages are called Gaucher
cells, and they accumulate in multiple organs and tissues, including the bone marrow, liver,
and spleen. While the reason is unclear, Gaucher cells and other nearby macrophages secrete
damaging lysosomal enzymes and inflammatory signals into the surrounding area. This causes
an immune response and production of scar tissue, resulting in many characteristic signs
and symptoms. GBA gene mutations are inherited in an autosomal recessive manner. There are a few subtypes of Gaucher disease.
In type 1, some individuals are asymptomatic, but when there are signs and symptoms they
can be due to bone marrow fibrosis, which causes reduced production of red blood cells,
resulting in anemia and associated fatigue. Rarely, white blood cells are also affected,
causing leukopenia. There can also be bone infarctions, caused by reduced blood flow
to part of a bone, can lead to a painful “bone crisis”, and result in physical deformity
and avascular necrosis, or death of bone tissue. Osteoporosis, or low bone density, is another
manifestation. Both the liver and spleen can become enlarged, and when platelets are sequestered,
or trapped, within the enlarged spleen, this can cause thrombocytopenia, or low platelets
in the blood. This can lead to bleeding and easy bruising. Type 2, also called acute neuronopathic Gaucher
disease, is characterized by severe neurological involvement early in life due to glucocerebroside
buildup in the brain. In addition to the symptoms associated with type 1, there’s also loss
of motor skills, decreased muscle tone, muscle spasms, and trouble swallowing. This can progress
to severe breathing and feeding difficulties, and death within the first few years of life. Lastly, type 3, also called chronic neuronopathic
Gaucher disease, is like type 2, but the symptoms develop at a slower rate, and in some individuals
can develop over decades. Seizures can be a major problem for some individuals with
type 3 Gaucher disease. Diagnosis of Gaucher disease relies on clinical
presentation, and measuring glucocerebrosidase enzyme activity with the beta-glucocerebrosidase
leukocyte blood test. Genetic testing can be done to look for mutations in the GBA gene. Treatment depends on the severity of the condition,
and can include enzyme replacement therapy with a synthetic form of glucocerebrosidase,
as well as substrate reduction therapy designed to block the enzyme that helps synthesizes
glucocerebroside. Symptoms can be managed with supportive therapy. All right, as a quick recap…Gaucher disease
is an inherited condition characterized by insufficient levels of glucocerebrosidase.
Glucocerebroside accumulates in the lysosomes of macrophages that accrue in multiple tissues
and cause damage. The types 2 and 3 forms of Gaucher disease involve the brain, while
type 1 does not. Diagnosis includes measuring the glucocerebrosidase enzyme activity and
genetic testing, and treatment includes a manufactured form of glucocerebrosidase.

4 thoughts on “Gaucher disease – causes, symptoms, diagnosis, treatment, pathology

  1. yessss please pass this on <3 I suffer from Gaucher type 1 it's very uncommon many doctors didn't diagnose it because of how rare it is.. please future doctors have this in your minds!!!

  2. Um Um Um … I didn’t understand a damn word so I’m just showing my doctor this video and ask him to make sure I don’t have whatever this video is talking about !!! ??????????

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