Test ID: BGA
Beta-Galactosidase, Leukocytes

Diagnosis of GM1 gangliosidosis and Morquio B disease

Not recommended for carrier detection.

Depending on the site of mutations within the same gene, 2 clinically distinct disorders can result from the subsequent deficiency of the lysosomal enzyme acid beta-galactosidase.

The first mutation, which affects the site specificity of the enzyme for GM1-gangliosides, leads to GM1-gangliosidosis. This autosomal recessive lysosomal storage disorder results in the accumulation of glycosphingolipids primarily in the gray matter of the brain. There are 3 clinical subtypes; presentation is presumably dependent on the level of residual enzyme activity in the cells. Infantile GM1 gangliosidosis, type 1, is the most common form of the disease and is characterized by early developmental delay, hepatosplenomegaly, coarse facial features, failure to thrive, and skeletal deformities. About 50% of patients have a cherry red spot in the retina. As the disease progresses, spasticity and seizures are common, with death occurring around age 2. Type 2, or juvenile GM1 gangliosidosis, progresses slower and is somewhat milder than type 1. It begins at about age 1. Development is normal at first, with loss of coordination and muscular strength later on. Additionally, mental and motor deterioration often progress rapidly. The course of the disease is similar to type 1. The average life span may vary between 3 and 10 years. The adult form of GM1 gangliosidosis, type 3, is very rare with only 20 families reported. Patients may be diagnosed in late childhood with progressive speech impairment and spasticity. In time, loss of intellectual function is evident.

The second mutation, which affects the site specificity of the enzyme for keratan sulphate, leads to Morquio type B syndrome (MPS-IVB). Also autosomal recessive, this disorder results in the accumulation of keratan sulphate primarily in the skeletal system. Characteristic features include short truncal dwarfism, scoliosis, odontoid hypoplasia, and vertebral deformities that worsen over time. There is typically no central nervous system involvement and intelligence is normal. Both mild and severe forms of the disease have been documented.

Enzyme replacement therapy is currently not available and treatment for both disorders is symptomatic and supportive. 

2.11-3.95 U/g protein

Very low enzyme activity levels are consistent with GM1 gangliosidosis and Morquio B disease. Clinical findings must be used to differentiate those 2 diseases.

At this time there is no known clinical significance to elevated enzyme levels.

This test is not suitable for carrier detection.

Suzuki Y, Sakuraba H, Oshima A: Beta-galactosidase deficiency In The Metabolic Basis of Inherited Disease. Vol. 3. 8th edition. Edited by CR Scriver, AL Beaudet, WS Sly, D Valle. New York, McGraw-Hill Book Company, 2001, chapter 151

• Lysosomal Storage Disorders
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