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Test ID: BGA Beta-Galactosidase, Leukocytes

Reporting Name

Beta-Galactosidase, Leukocytes

Useful For

Diagnosis of GM1 gangliosidosis, Morquio B disease, and galactosialidosis

Specimen Type

Whole Blood ACD


Shipping Instructions


For optimal isolation of leukocytes, it is recommended the specimen arrive refrigerated within 72 hours of draw to be stabilized. Draw specimen Monday through Thursday only and not the day before a holiday. Specimen should be drawn and packaged as close to shipping time as possible.



Specimen Required


Container/Tube:

Preferred: Yellow top (ACD solution B)

Acceptable: Yellow top (ACD solution A)

Specimen Volume: 6 mL

Collection Instructions: Do not transfer blood to other containers.


Specimen Minimum Volume

5 mL

Specimen Stability Information

Specimen Type Temperature Time
Whole Blood ACD Refrigerated (preferred) 72 hours
  Ambient  72 hours

Reference Values

≥1.56 nmol/min/mg

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday.

Assay is performed on Monday; Varies.

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

82657

LOINC Code Information

Test ID Test Order Name Order LOINC Value
BGA Beta-Galactosidase, Leukocytes 24061-4

 

Result ID Test Result Name Result LOINC Value
8486 Beta-Galactosidase, Leukocytes 24061-4
34979 Interpretation (BGA) 59462-2
34907 Reviewed By No LOINC Needed

Clinical Information

Beta-galactosidase is a lysosomal enzyme responsible for catalyzing the hydrolysis of gangliosides. The deficiency of this enzyme can lead to 1 of the following conditions: GM1 gangliosidosis, Morquio syndrome B, and galactosialidosis. Enzymatic testing is not reliable for carrier detection of these conditions.

 

GM1 gangliosidosis is an autosomal recessive lysosomal storage disorder caused by reduced or absent beta-galactosidase activity. Absent or reduced activity leads to the accumulation of GM1 gangliosides, oligosaccharides, and keratan sulfate. The disorder can be classified into 3 subtypes that vary with regard to age of onset and clinical presentation. Type 1, or infantile onset, typically presents between birth and 6 months with a very rapid progression of hypotonia, dysostosis multiplex, hepatosplenomegaly, central nervous system degeneration, and death usually by 1 to 2 years. Type 2 is generally classified as late infantile or juvenile with onset between 7 months and 3 years and presenting with developmental delays or regression and a slower clinical course. Type 3 is an adult or chronic variant with onset between 3 and 30 years and is typically characterized by slowly progressive dementia with Parkinsonian features and dystonia. The incidence has been estimated to be 1 in 100,000 to 200,000 live births.

 

Morquio B (MPS IVB) is an autosomal recessive mucopolysaccharidosis caused by reduced or absent beta-galactosidase activity resulting in the accumulation of keratan sulfate in the lysosomes. The mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans: GAG). Accumulation of GAG in lysosomes interferes with normal functioning of cells, tissues, and organs. MPS IVB typically manifests as a systemic skeletal disorder with variable severity ranging from early severe disease to a later onset attenuated form. Virtually all patients have dysostosis multiplex and short stature along with other symptoms that may include coarse facies, hepatosplenomegaly, hoarse voice, stiff joints, cardiac disease, but no neurological involvement.

 

Galactosialidosis is an autosomal recessive lysosomal storage disease (LSD) associated with a combined deficiency of beta-galactosidase and neuraminidase secondary to a defect in the cathepsin A protein. Clinical features are those typically associated with LSDs including coarse facial features, cherry-red spots, or skeletal dysplasia. The disorder can be classified into 3 subtypes that vary with respect to age of onset and clinical presentation. The early infantile form is associated with fetal hydrops, visceromegaly, skeletal and ophthalmologic disorders, and early death. The late infantile form typically presents with short stature, dysostosis multiplex, coarse facial features, hepatosplenomegaly, and/or heart valve problems. The juvenile/adult form is characterized by progressive neurologic degeneration, ataxia, cognitive disability, and/or angiokeratomas. Most of the juvenile/adult form cases have been found in individuals with Japanese ancestry.

 

Patients with mucolipidosis II/III (I-cell disease) may also demonstrate deficiency of beta-galactosidase in leukocytes, in addition to deficiency of other hydrolases. I-cell disease is an autosomal recessive lysosomal storage disorder resulting in impaired transport and phosphorylation of newly synthesized lysosomal proteins to the lysosome due to deficiency of N-acetylglucosamine 1-phosphotransferase (GlcNAc). Characteristic clinical features include short stature, skeletal and cardiac abnormalities, and developmental delay. Measurement of beta-galactosidase activity is not the preferred diagnostic test for I-cell disease, but may be included in the testing strategy.

 

A diagnostic workup in an individual with GM1 gangliosidosis, Morquio B, or galactosialidosis typically demonstrates decreased beta-galactosidase enzyme activity in leukocytes and/or fibroblasts; however, additional testing and consideration of the patient's clinical findings are necessary to differentiate between these conditions. Individuals with GM1 gangliosidosis can have characteristic abnormalities on urine oligosaccharides and have elevated keratan sulfate in urine (however, to a lesser degree than seen in patients with Morquio B). Individuals with Morquio B can have increased keratan sulfate in urine. Molecular sequence analysis of the GLB1 gene allows for detection of the disease-causing mutations in affected patients with GM1 gangliosidosis and Morquio B. Individuals with galactosialidosis also demonstrate abnormalities on urine oligosaccharides as well as decreased neuraminidase activity in fibroblasts. Enzymatic testing is not reliable to detect carriers. Sequencing of the CTSA gene allows for detection of disease-causing mutations in patients with galactosialidosis.

Interpretation

Very-low enzyme activity levels are consistent with GM1 gangliosidosis and Morquio B disease. Clinical findings must be used to differentiate between those 2 diseases. The deficiency of beta-galactosidase combined with neuraminidase deficiency (see NEURF / Neuraminidase, Fibroblasts) is characteristic of galactosialidosis.

Clinical Reference

1. Suzuki Y, Nanba E, Matsuda J: Galactosidase Deficiency (Beta-Galactosidosis): GM1 Gangliosidosis and Morquio B Disease. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill; 2014. Accessed January 27, 2017. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62645114

2. d'Azzo A, Andria G, Bonten E, Annunziata I: Chapter 152: Galactosialidosis. In The Metabolic Basis of Inherited Disease. 2014. Edited by D Valle, AL Beaudet, B Vogelstein. New York, McGraw-Hill Book Company. Accessed 01/16/2015. Available at www.ommbid.com

3. Brunetti-Pierri N, Scaglia F: GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab 2008 Aug;94(4):391-396

4. Caciotti A, Garman SC, Rivera-Colon Y, et al: GM1 gangliosidosis and Morquio B disease: an update on genetic alterations and clinical findings. Biochim Biophys Acta 2011 Jul;1812(7):782-790

Analytic Time

8 days

Method Name

Fluorometric

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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