Clinical Information

Gaucher disease is an autosomal recessive lysosomal storage disorder caused by a deficiency of the enzyme, beta-glucosidase. Beta-glucosidase facilitates the lysosomal degradation of glucosylceramide (glucocerebroside) and glucopsychosine (glucosylsphingosine: lyso-GL1). Gaucher disease is caused by variants in the GBA gene. There are 3 described types of Gaucher disease with varying clinical presentations and age of onset from a perinatal lethal disorder to an asymptomatic type. Features of all types of Gaucher disease include hepatosplenomegaly and hematological abnormalities.

Gaucher disease type I is the most common form, representing more than 90% of cases. It is generally characterized by bone disease, hepatosplenomegaly, anemia and thrombocytopenia, coagulation abnormalities, lung disease, but no central nervous system (CNS) involvement. Gaucher disease types II and III are characterized by the presence of primary neurologic disease. In addition, Type II typically presents with limited psychomotor development, hepatosplenomegaly, and lung disease, resulting in death usually between 2 and 4 years of age. Individuals with Gaucher disease type III may present prior to 2 years of age, but the progression is not as rapid and patients may survive into the third and fourth decade. Additional subtypes of Gaucher disease include a perinatal lethal form associated with skin abnormalities and nonimmune hydrops fetalis, and a cardiovascular form presenting with calcification of the aortic and mitral valves, mild splenomegaly, corneal opacities, and gaze impairment.

Treatment is available in the form of enzyme replacement therapy and substrate reduction therapy for types I and III. These treatment options have generally made bone marrow transplantation obsolete. Currently, only supportive therapy is available for type II because of the inability of enzyme provided by replacement therapy to cross the blood-brain barrier.

The incidence of Gaucher disease type I ranges from 1 in 30,000 to 1 in 100,000 in the general population, but is much more frequent among Ashkenazi Jews with an incidence of approximately 1 in 900. Types II and III both have an incidence of approximately 1 in 100,000 in the general population.

A diagnostic workup for Gaucher disease may demonstrate the characteristic finding of Gaucher cells on bone marrow examination, other hematologic abnormalities, and hepatosplenomegaly. The diagnosis can be confirmed by the demonstration of reduced or absent acid beta-glucosidase activity in leukocytes (BGL / Beta-Glucosidase, Leukocytes), or dried blood spots (PLSD / Lysosomal and Peroxisomal Storage Disorders Screen, Blood Spot) and molecular genetic analysis of the GBA gene (GAUP / Gaucher Disease, Mutation Analysis, GBA, Varies; or GBAZ / Gaucher Disease, Full Gene Analysis, Varies). Lyso-GL1 is elevated in symptomatic patients and supports a diagnosis of Gaucher disease. It may also be helpful in determining treatment response.