Prevalence and Incidence • Overall incidence of 1 in 40,000 to 1 in 60,000 live births. Incidence is much higher (1 in 850) in people with Ashkenazi Jewish ancestry.  • All forms of Gaucher Disease affect males and females in equal numbers.  • The carrier frequency in general population is 0.7 to 0.8%, while in Ashkenazi Jewish population is 6%.
	Age of onset • Delays in diagnosis of up to 10 years are not uncommon.  • Age at presentation from GD type 2 occurs around infancy and type 3 around childhood.

 

General symptoms include anemia, thrombocytopenia, chronic fatigue, bleeding, splenomegaly, and bone involvement. 

Type 1 is the most common and least severe form, typically presenting in adulthood with:

• Hepatosplenomegaly.
• Anemia.
• Thrombocytopenia.
• Bone pain.
• Osteopenia.
• Fractures.

Type 2 and type 3 are more severe and usually present in infancy or childhood.

Type 2 presents with severe neurological symptoms such as:

• Seizures.
• Strabismus.
• Oculomotor apraxia.
• Hypertonia.

Type 3 has neurological symptoms that develop more slowly, most often including slowing of the horizontal saccadic eye movements, and may not be as severe as in type 2.

All types can present with:

• Osteoporosis.
• Avascular necrosis of the femur.
• Pancytopenia.
• Pulmonary manifestations.
• Failure to thrive. 

Gaucher disease can be diagnosed by enzyme assay, and DNA testing.

Enzymatic testing of peripheral blood samples is the definitive diagnostic tool; results of the assay directly identify the causal enzyme deficiency in leukocytes. However, false negatives or positives are not uncommon (up to 30%) when enzyme testing is used to detect carrier status.

The decreased acid β-glucosidase activity in peripheral blood leukocytes or dried blood spots, and genetic testing are currently options for the diagnostic for Gaucher. Enzyme testing is diagnostic but not predictive of clinical course; residual enzyme activity is not associated with clinical outcomes.

Sequencing of the GBA gene can provide additional diagnostic confirmation, potential delineation of type of Gaucher, and overall insight into disease progression.

Biochemical markers such as chitotriosidase and chemokine CC motif ligand 18 (CCL18) may be used as supplementary diagnostic tools. Elevations in the chemokine CCL18 are indicative of Gaucher disease but may not proportionally reflect symptom severity.

Lyso-Gb1 is the most promising biomarker of GD, as demonstrated by its reliability in reflecting disease burden and monitoring treatment response. Furthermore, lyso-Gb1 has an important role in the pathogenetic mechanism of PD due to its cerebral accumulation, and in B-cell lymphoproliferative disorders, such as multiple myeloma, due to humoral immunity dysregulation by chronic antigenic stimulation.

The treatment of Gaucher’s disease aims to manage the clinical signs and symptoms of the disease and prevent complications.

Two treatment approaches are currently available for Gaucher type 1: enzyme replacement therapy (ERT) with recombinant acid-β-glucosidase, and substrate reduction therapy (SRT).

Bone marrow transplantation may also be considered in certain cases.

The complications of Gaucher disease can lead to premature mortality; estimated life expectancy among patients with GD1 is about 9 years lower compared with the US general population.

Delays in the diagnosis of Gaucher disease can lead to severe, sometimes irreversible complications, including bone complications (e.g., chronic bone pain, osteonecrosis, osteofibrosis, lytic lesions, AVN, and bone crises), severe and life-threatening bleeding, growth failure, and functional and symptomatic consequences of visceromegaly (e.g., acute abdominal pain).

Common complications include Parkinson disease   and increased risk of malignancy such as multiple myeloma and lymphoma. Type 2 Gaucher disease, also known as infantile Gaucher disease, has a poor prognosis with death occurring within the first years of life. Neurodegeneration is a common complication in type 3 Gaucher disease, also known as juvenile Gaucher disease.