Test ID: BGAW    
Beta-Galactosidase, Blood

Diagnosis of GM1 gangliosidosis,  Morquio syndrome B, and galactosialidosis in whole blood specimens

This test is not useful for carrier detection.

Beta-galactosidase enzyme is deficient in the following conditions: GM1 gangliosidosis, Morquio syndrome B, and galactosialidosis.

See Lysosomal Storage Disorders Diagnostic Algorithm, Part 1 in Special Instructions.

Beta-galactosidase is a lysosomal enzyme responsible for catalyzing the hydrolysis of gangliosides. Isolated deficiency of this enzyme is expressed clinically as 2 different autosomal recessive diseases, GM1 gangliosidosis and Morquio syndrome B (MPS IVB, Morquio B). Galactosialidosis (GS) is also associated with a deficiency of beta-galactosidase, but in conjunction with neuraminidase deficiency secondary to a defect in protective protein cathepsin A (PPCA). Enzymatic testing is not reliable for carrier detection of these conditions.

In GM1 gangliosidosis, reduced or absent beta-galactosidase 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 presenting with developmental delays and a slower progression. 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.

In MPS IVB, reduced or absent beta-galactosidase activity leads to the accumulation of glycosaminoglycans (GAG) in lysosomes and 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 caused by variants in the cathepsin A gene (CTSA) resulting in a combined deficiency of the enzymes beta-galactosidase and neuraminidase. The disorder can be classified into 3 subtypes that vary with regard to age of onset and clinical presentation. Typical clinical presentation includes coarse facial features, cherry-red spots, and skeletal dysplasia. The early infantile form is associated with fetal hydrops, visceromegaly, skeletal dysplasia, and early death. The late infantile form typically presents with short stature dysostosis multiplex, coarse facial features, corneal clouding, hepatosplenomegaly, and/or heart valve problems. The majority of individuals with the juvenile/adult form of GS are of Japanese ancestry and develop symptoms after 4 years of age, which include neurologic degeneration, ataxia, and angiokeratomas.

A diagnostic workup in an individual with GM1 gangliosidosis, MPS IVB, or GS typically demonstrates decreased beta-galactosidase enzyme activity in leukocytes or fibroblasts; however, additional testing and consideration of the patient's clinical findings are necessary to differentiate between these conditions. Follow-up testing may include LYSDU / Lysosomal Storage Disorders Screen, Urine, which analyzes urine mucopolysaccharides, oligosaccharides, ceramide trihexosides, and sulfatides. The  Lysosomal storage disorders screencan help differentiate between the 3 conditions to guide physicians in choosing the best confirmatory molecular testing option.

> or =5.0 nmol/hour/mL

An interpretive report will be provided.

Results below 5.0 nmol/hour/mL in properly submitted specimens are consistent with beta-galactosidase deficiency (GM1 gangliosidosis, MPS IVB, or galactosialidosis). Further differentiation between GM1, MPS IVB, and galactosialidosis is dependent on the patient's clinical findings and results of additional biochemical testing.

Normal results (> or =5.0 nmol/h/mL) are not consistent with beta-galactosidase deficiency.

This test cannot reliably determine carrier status.

This test does not differentiate between GM1 gangliosiosis, MPS IVB, and galactosialidosis.

1. Suzuki Y, Nanba E, Matsuda J, et al: Beta-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. Accessed 3/11/2019. Available at

https://ommbid.mhmedical.com/content.aspx?sectionid=225547263&bookid=2709&Resultclick=2

2. Chamoles NA, Blanco M, Gaggioli D, Casentini C: Hurler-like phenotype: enzymatic diagnosis in dried blood spots on filter paper. Clin Chem 2001 Dec;47(12):2098-2102

3. Regier DS, Tifft CJ: GLB1-Related Disorders. In GeneReviews. Edited by RA Pagon, MP Adam, HH Ardinger, et al. Updated 29 Aug 2019. Accessed 1/30/2017. Available at www.ncbi.nlm.nih.gov/books/NBK164500/

4. d'Azzo A, Andria G, Bonten E, Annunziata I: Galactosialidosis. In The Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill. Accessed 3/11/2019. Available at https://ommbid.mhmedical.com/content.aspx?sectionid=225547663&bookid=2709&Resultclick=2

• Informed Consent for Genetic Testing
• Biochemical Genetics Patient Information
• Informed Consent for Genetic Testing (Spanish)
• Lysosomal Storage Disorders Diagnostic Algorithm, Part 1