AssessmentsGaucher disease (NORD)
Gaucher disease (NORD)
The gold standard for the diagnosis of Gaucher disease is .
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A 45-year-old woman presents to her physician complaining of intense hip and leg pain. The pain is severe enough to limit movement and wake her from sleep. Upon physical exam, severe hepatomegaly and splenomegaly are noted. Blood is drawn and a complete blood count obtained:RBCs: 3*106 cells/microliter (normal 3.8-5.3*106/uL)WBCs: 3.8*103 cells/microliter (normal 4.5-11 *103/uL)Platlets: 50*103 /microliter (normal 150-440 *103/uL)Hematocrit: 33% (35-47%)Hemoglobin: 10 g/dL (normal 11.7-16.0 g/dL)
An MRI of the thigh was also obtained:
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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.