GBA 2 gene

The GBA gene (GBA stands for glucosylceramidase beta) is a protein-coding gene located on chromosome 1q22. This gene encodes a lysosomal membrane protein that cleaves the beta-glucoside bond of glycosylceramide, an intermediate in glycolipid metabolism.

Mutations in this gene cause Gaucher syndrome, a lysosomal storage disease characterized by accumulation of glucocerebrosides. A related pseudogene is located approximately 12 kb downstream of this gene on chromosome 1. Alternative splicing results in multiple transcript variants.

Diseases associated with GBA include:

• Gaucher syndrome, type 1
• Gaucher syndrome, type 2

Gaucher syndrome is caused by beta-glucocerebrosidase (also called glucosylceramidase or acid beta-glucosidase) activity deficiency.

Type 2 Gaucher syndrome is a rare, autosomal recessive neurologically accentuated form of the disease and accounts for only 1% of all cases. Tsuji et al (1987) identified a homozygous mutation in the GBA gene (L444P; 606463.0001) in patients with Gaucher type II disease.

Symptoms usually begin in infancy, during the first 3 to 6 months of life, with hepatosplenomegaly and a severe neurologic syndrome. The first signs of the disease are oculomotor paralysis or bilateral fixed strabismus, bulbar signs, especially in the form of dysphagia, and progressive spasticity and dystonic movements. Later, cerebral convulsions occur in the form of myoclonic epilepsy that does not respond to anticonvulsants.

1. Daykin EC et al (2021) Diagnosing neuronopathic Gaucher disease: new considerations and challenges in assigning Gaucher phenotypes. Molec Genet Metab 132: 49-58.
2. Filocamo M et al (2005) Homozygosity for a non-pseudogene complex glucocerebrosidase allele as cause of an atypical neuronopathic form of Gaucher disease. (Letter) Am J Med Genet 134A: 95-96.
3. Goker-Alpan O et al.(2003) Phenotypic continuum in neuronopathic Gaucher disease: an intermediate phenotype between type 2 and type 3. J Pediat 143: 273-276.
4. Grace ME et al (1990) Gaucher disease: a molecular basis for the type 2 and type 3 phenotypes. (Abstract) Am J Hum Genet 47 (suppl.): A156 only.
5. Tsuji S et al (2001) A mutation in the human glucocerebrosidase gene in neuronopathic Gaucher's disease. New Eng J Med 316: 570-575.