Gaucher Disease

Gaucher disease is a rare genetic disorder in which a person lacks an enzyme called glucocerebrosidase. This results in a fatty material, or lipid, accumulating in the body. Avascular Necrosis and bone fractures are common orthopedic manifestations of this disease.

The signs and symptoms of the condition can vary considerably. Several different types of gaucher disease have been proposed:

  • Type 1 - Non-neuronopathic
    • The most common form
    • Central nervous system not affected
    • Symptoms include enlargement of liver, low red blood cell count, thrombocytopenia, lung disease, and bone abnormalities (i.e. fractures, arthritis)
    • Typically manifests in early life or adulthood
  • Type 2 - Neuronopathic
    • Central nervous system is affected
    • Symptoms include abnormal eye movements, seizures, and brain damage
    • Usually causes life-threatening medical problems
    • Typically manifests within 6 months of birth
  • Type 3 - Neuronopathic
    • Similar to type 2, but onset is slower and milder
    • Typically manifests in early life or adulthood

Another, severe form of Gaucher disease has also been proposed: perinatal lethal form. This condition causes severe life-threatening conditions before birth. Most infants with this type do not survive a few days after birth.

Gaucher disease occurs in 1 in 50,000 to 100,000 live births. Type 1 is significantly more common than the other types. Type 1 Gaucher disease occurs more frequently in individuals with Ashkenazi Jewish heritage (at a rate of 1 in 500 to 1,000 live births).

Gaucher disease has been linked to mutations in the GBA gene. The GBA gene is responsible for making an enzyme, glucocerebrosidase, that processes glucocerebrosides in the body. In unaffected individuals glucocerebrosidase breaks down glucocerebrosides into sugar and simple fat molecules. Without this process glucocerebrosides accumulate in the cells causing the characteristic features of Gaucher disease. 

Mutations to the GBA gene are inherited in a recessive pattern. Affected individuals carry both copies of the mutated gene. Parents carry the recessive allele but do not show signs and symptoms of Gaucher disease.

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