Glucopsychosine, Blood Spot
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
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). Gaucher disease is caused by mutations 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, 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. Further 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/or 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) and molecular genetic analysis of the GBA gene (GAUP / Gaucher Disease, Mutation Analysis, GBA; or GBAZ / Gaucher Disease, Full Gene Analysis). Glucopsychosine is elevated in symptomatic patients and supports a diagnosis of Gaucher disease. It may also be helpful in determining treatment response.
Quantification of glucopsychosine (glucosylsphingosine) in dried blood spots supports the biochemical diagnosis of Gaucher disease
May aid in monitoring a patientâ€™s response to treatment
An elevation of glucopsychosine is indicative of Gaucher disease.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not capable of identifying carriers of GBA mutations.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
Normal <47 nmol/L glucopsychosine
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Orvisky E, Park J, LaMarca M, et al: Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype. Mol Genet Metab 2002;76:262-270
2. Pastores GM, Hughes DA: Gaucher Disease. In GeneReviews Edited by RA Pagon, MP Adam, HH Ardinger, et al: University of Washington, Seattle, 1993-2015. 2000 Jul 27 (Updated 2015 Feb 26). Available at http://www.ncbi.nlm.nih.gov/books/NBK1269/
3. Dekker N, Dussen L, Hollak C, et al: Elevated plasma glucosylsphingosine in Gaucher disease: relation to phenotype, storage cell markers, and therapeutic response. Blood 2011;118(16):118-127
4. Kaplan P, Baris H, De Meirleir L, et al: Revised recommendations for the management of Gaucher disease in children. Eur J Pediatr 2013;172:447-458
5. Grabowski GA, Petsko GA, Kolodny EH: Gaucher Disease. In The Online Metabolic and Molecular Bases of Inherited Diseases. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York. McGraw-Hill, 2013, Accessed January 21, 2014.
6. Murugeasan V, Chuan WL, Liu J, et al: Glycosylsphingosine is a key biomarker of Gaucher disease. Am J Hematol 2016; EPub ahead of print