Wednesday, March 29, 2023

Gaucher Disease

Practice Essentials

Gaucher disease is a rare genetic disorder characterized by the deposition of glucocerebroside in cells of the macrophage-monocyte system. The disorder results from the deficiency of the enzyme glucocerebrosidase.

Signs and symptoms

While Gaucher disease manifests with vast clinical heterogeneity, it has traditionally been differentiated into the following three clinical subtypes, delineated by the absence or presence of neurologic involvement and its progression:

Type 1 – Nonneuronopathic Gaucher disease

Type 2 – Acute neuronopathic Gaucher disease

Type 3 – Chronic neuronopathic Gaucher disease

Patients with type 1 disease commonly present with painless splenomegaly, anemia, or thrombocytopenia. They may also have chronic fatigue, hepatomegaly (with or without abnormal liver function test findings), bone pain, or pathologic fractures and may bruise easily because of thrombocytopenia. Bleeding secondary to thrombocytopenia may manifest as nosebleeds, bruising, or both.

Patients with type 2 disease may present at birth or during infancy with increased tone, seizures, strabismus, and organomegaly. Failure to thrive, swallowing abnormalities, oculomotor apraxia, hepatosplenomegaly, and stridor due to laryngospasm are typical in infants with type 2 disease.

In addition to organomegaly and bony involvement, individuals with type 3 disease have neurologic involvement, most often including slowing of the horizontal saccadic eye movements.

See Clinical Presentation for more detail.


Diagnosis can be confirmed through measurement of glucocerebrosidase activity in peripheral blood leukocytes. A finding of less than 15% of mean normal activity is diagnostic. Minor elevations of liver and angiotensin-converting enzyme levels are common. DNA analysis is also used to establish the diagnosis based on presence of two mutant alleles, especially in diagnostic panels.

See Workup for more detail.


Enzyme replacement therapy (ERT) is indicated for patients with type 1 and type 3 Gaucher disease who exhibit clinical signs and symptoms of the disease, including anemia, thrombocytopenia, skeletal disease, or visceromegaly. Substrate reduction therapy (SRT) is an alternative treatment for appropriate adult patients with type 1 Gaucher disease. SRT works via global reduction of glucosylceramide synthase and has been shown to yield outcomes similar to those of ERT in adults.

See Treatment and Medication for more detail.

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