Clinical Information

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by reduced or absent acid beta-glucosidase (glucocerebrosidase) enzyme activity resulting in accumulation of glucosylceramide (glucocerebroside) and glucopsychosine (glucosylsphingosine) in the lysosomes. This interferes with the normal functioning of cells and leads to clinical abnormalities characteristic of the disease.

While clinical features and severity of symptoms are widely variable within Gaucher disease, common features include abnormal blood parameters such as decreased red blood cells (anemia) and/or platelets (thrombocytopenia), bone disease, and hepatosplenomegaly. Three clinical subtypes have been identified based on the presence and progression of central nervous system (CNS) involvement. Type 1 is the most common type, representing 95% of all cases, and is generally characterized by bone disease, hepatosplenomegaly, anemia and thrombocytopenia, coagulation abnormalities, lung disease, and no CNS involvement. Type 2 or acute neuronopathic (GD2), typically has a very severe progression with onset in the first 2 years of life including neurologic disease, hepatosplenomegaly, and lung disease, with death usually between 2 and 4 years due to lung failure. Individuals with type 3 or chronic neuronopathic (GD3) may have onset prior to 2 years of age, but the progression is not as severe, and they may survive into the third and fourth decade. Finally, within the spectrum, there is 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, and corneal opacities.

Treatment is available in the form of enzyme replacement therapy (ERT), substrate reduction therapy, and chaperone therapy for types 1 and 3. Individuals with type 3 may benefit from bone marrow transplantation. Currently, only supportive therapy is available for type 2. Emerging therapies currently listed at Clinicaltrials.gov include gene therapy and in utero ERT.

The incidence of type 1 ranges from 1 in 20,000 to 200,000 in the general population, but it is much more frequent among Ashkenazi Jewish population with an incidence between 1 in 400 and 900. Types 2 and 3 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. Significantly reduced or absent enzyme activity of acid beta-glucosidase along with elevation of the biomarker, glucopsychosine (GPSY / Glucopsychosine, Blood Spot; GPSYP / Glucopsychosine, Plasma; GPSYW / Glucopsychosine, Blood) is diagnostic. Molecular analysis of the GBA gene allows for detection of disease-causing variants in affected patients (GBAZ / Gaucher Disease, Full Gene Analysis, Varies or CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies [specify GBA Gene List ID IEMCP-M4F13T]).