Clinical Information

Beta-galactosidase is a lysosomal enzyme responsible for catalyzing the breakdown of gangliosides. Isolated deficiency of this enzyme is expressed clinically as 2 different autosomal recessive diseases, GM1 gangliosidosis and Morquio syndrome B (mucopolysaccharidosis IVB [MPS IVB] or Morquio B). Galactosialidosis (GS) is associated with a combined deficiency of beta-galactosidase and neuraminidase secondary to a defect in protective protein cathepsin A. 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 respect to age of onset and clinical presentation. Type 1, or infantile onset, typically presents between birth and 6 months of age with a very rapid progression of hypotonia, dysostosis multiplex, hepatosplenomegaly, central nervous system degeneration, and death usually by 1 to 2 years of age..Type 2 is generally classified as late infantile or juvenile with onset between 7 months and 3 years of age presenting with developmental delays and a slower progression. Type 3 is an adult or chronic variant with onset between 3 and 30 years of age 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 Morquio B, reduced or absent beta-galactosidase activity leads to the accumulation of glycosaminoglycans, particularly keratan sulfate, in lysosomes and interferes with normal functioning of cells, tissues, and organs. Morquio B 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 respect 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, while the late infantile form is characterized by short stature, dysostosis multiplex, coarse facial features, corneal clouding, hepatosplenomegaly, and/or heart valve problems. Individuals of Japanese ancestry make up the majority of patients with the juvenile/adult form of GS and typically develop symptoms after 4 years of age. These include neurologic degeneration, ataxia, and angiokeratomas.

A diagnostic workup in an individual with GM1 gangliosidosis, Morquio B, 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 LSDS / Lysosomal Storage Disorders Screen, Random, Urine, which analyzes urine mucopolysaccharides, oligosaccharides, ceramide trihexosides, and sulfatides. The LSDS test can help differentiate between the 3 conditions to guide physicians in choosing the best confirmatory molecular testing option. See Lysosomal Storage Disorders Diagnostic Algorithm, Part 1 .