Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
A deficiency of the beta galactosidase enzyme can lead to the following autosomal recessive lysosomal storage disorders: GM1 gangliosidosis, Morquio syndrome B, and galactosialidosis.
GM1 gangliosidosis can result from reduced or absent beta-galactosidase activity leading to the accumulation of GM1 gangliosides, oligosaccharides, and keratan sulfate. This 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.
Mucopolysaccharidosis type IVB (MPS IVB, Morquio B) is caused by reduced or absent beta-galactosidase activity. The mucopolysaccharidoses are a group of disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of glycosaminoglycans (GAGs). Clinical features and severity of symptoms of MPS IVB are widely variable ranging from severe disease to an attenuated form, which generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, short stature, hepatosplenomegaly, hoarse voice, stiff joints, cardiac disease, but no neurological involvement. The incidence has been estimated to be 1 in 100,000 to 200,000 live births.
Galactosialidosis is disease associated with a combined deficiency of beta-galactosidase and neuraminidase secondary to a defect in the cathepsin A protein. The disorder can be classified into 3 subtypes that vary with regard to age of onset and clinical presentation. Typical clinical presentation is coarse facial features, cherry-red spots, or skeletal dysplasia. The early infantile form is associated with fetal hydrops, skeletal dysplasia, 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 typically characterized by progressive neurologic degeneration, ataxia, and/or angiokeratomas. The incidence of the juvenile/adult form is greater in individuals with Japanese ancestry.
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. Enzymatic testing is not reliable to detect carriers. Individuals with galactosialidosis would also have decreased neuraminidase activity in leukocytes and/or fibroblasts in addition to decreased beta-galactosidase enzyme activity. Molecular sequencing of the GLB1 gene allows for detection of the disease-causing mutations in affected patients with GM1 gangliosidosis and/or Morquio B and sequencing of the CTSA gene allows for detection of disease-causing mutations in patients with galactosialidosis.
Diagnosis of GM1 gangliosidosis, Morquio syndrome B, and galactosialidosis
Beta-galactosidase is deficient in GM1 gangliosidosis and Morquio syndrome B. The deficiency of beta-galactosidase combined with neuraminidase deficiency is characteristic of galactosialidosis.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
This test is not suitable for carrier detection.
Leukocytes are the preferred specimen for the diagnosis of GM1 gangliosidosis.
Because beta-galactosidase is decreased in 3 clinically distinct disorders, a careful review of the clinical findings is necessary to differentiate between GM1 gangliosidosis and Morquio syndrome B. Patients with galactosialidosis will also exhibit decreased neuraminidase values in addition to decreased beta-galactosidase.
Interfering factors include lack of viable cells, bacterial contamination, failure to transport tissue in an appropriate media, excessive transport time, and exposure of the specimen to temperature extremes (freezing or >30 degrees C).
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.
> or =7.11 nmol/min/mg protein
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Suzuki Y, Sakuraba H, Oshima A: Beta-galactosidase deficiency (GM1 gangliosidosis, Morquio's syndrome type B). In The Metabolic Basis of Inherited Disease. Vol 2. Seventh edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. New York, McGraw-Hill Book Company, 1995, pp 2785-2838
2. Brunetti-Pierri N, Scaglia F: GM1 gangliosidosis: review of clinical, molecular, and therapeutic aspects. Mol Genet Metab 2008 Aug;94(4):391-396
3. 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