Gaucher disease (NORD)
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AssessmentsGaucher disease (NORD)
Gaucher disease (NORD)
USMLE® Step 1 style questions USMLE
An 8-year-old boy is brought to the emergency room for evaluation of severe hip pain over the past several hours. His parents have noticed that he has begun to walk with a limp due to pain in his right hip over the last 2 weeks, which acutely worsened today. His past medical history is significant for recurrent upper respiratory infections over the past 2 years. The patient has also had multiple episodes of epistaxis over the past year. His birth and developmental history are unremarkable, and his immunizations are up to date. His family is of Ashkenazi Jewish descent. Vitals are within normal limits. A complete physical examination is unable to be performed because of irritability and severe hip pain. Complete blood counts are shown below:
|Complete blood count|
|Leukocyte count||2,100 /mm3|
MRI of the right hip reveals avascular necrosis. The physician suspects a genetic disorder. Which of the following is most likely to be seen on further examination?
Gaucher disease (NORD) exam links
Content Reviewers:Rishi Desai, MD, MPH, Viviana Popa, MD
Contributors:Evan Debevec-McKenney, Jung Hee Lee, MScBMC
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.
Gaucher disease (GD) is a rare, inherited disorder that affects the body's ability to break down glucocerebroside molecules, because there is a lack of an enzyme called glucocerebrosidase that normally breaks down this molecule. This results in the accumulation of glucocerebrosidase in the lysosomes of macrophages, and other tissues, in different parts of the body.
There are three major types of Gaucher disease, depending on which tissues are most affected. In type 1 Gaucher disease, bone marrow cells are the most affected, which can lead to bone marrow fibrosis and anemia, and hepatosplenomegaly. In type 2 Gaucher disease, neurons in the brain are damaged and symptoms progress rapidly, resulting in death within the first few years. Finally, type 3 Gaucher disease is like type 2, but the symptoms develop at a slower rate.