Gaucher Disease: Beta-glucosidase Enzyme Analysis

Clinical Information

Gaucher disease, a lysosomal storage disease (LSD), presents with a wide spectrum of severity, ranging from a perinatal lethal phenotype to asymptomatic cases. There are three primary types and two additional subtypes, categorized by differences in clinical presentation. Common features across most types include hepatosplenomegaly, pulmonary disease, and cytopenia.

Gaucher disease type 1 is characterized by varying degrees of bone disease as the primary feature, without central nervous system involvement. Types 2 and 3 present with primary neurologic disease and are distinguished by age of onset and disease progression. Type 2 typically begins before age 2, with rapid progression and early death. Type 3 has a slower course, with patients often surviving into adulthood. Neurologic findings in types 2 and 3 include bulbar and pyramidal signs, oculomotor apraxia, seizures, and, in later stages, dementia and ataxia. The perinatal lethal form may present with nonimmune hydrops fetalis or with pyramidal neurologic signs and ichthyosiform skin changes. The cardiovascular form is characterized primarily by calcification of the mitral and aortic valves, along with other minor findings.

Technical Information

Beta-glucosidase enzyme activity is measured using a 4-methylumbelliferyl (4-MU) substrate (leukocytes, fibroblasts) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) (DBS).

Specimen Requirements

• Accepted sample types for this test include dried blood spots (DBS), fibroblasts, and leukocytes.
• DBS: Approximately 75 uL of blood should be applied to each of the five circles on filter paper dried blood spot card. Allow blood to dry for at least 4 hours before shipping.
• Fibroblasts: Tissue sample should be stored in sterile culture media; cultured fibroblasts should be sent in two T25 flasks. Do NOT place tissue in formalin or formaldehyde. Do not freeze tissue.
• Leukocytes: A minimum of 5 mL whole blood (7-10 mL preferred) collected in a sodium heparin tube.

Transport Instructions

• DBS: Ship DBS card at ambient temperature.
• Fibroblasts: Ship tissue sample or cultured fibroblasts at ambient temperature
• Leukocytes: Whole blood should be shipped at ambient temperature. If leukocytes are being isolated at another laboratory, the pellet should be frozen after specimen processing and shipped frozen on dry ice.