GM1 Gangliosidosis: GLB1 Gene Deletion/Duplication

Condition Description

GM1-gangliosidosis and Morquio B disease are both rare autosomal recessive lysosomal storage disorders caused by a deficiency of the enzyme beta-galactosidase (GLB1; E.C. due to mutations in the GLB1 gene. The enzyme has a catalytic effect on the ganglioside GM1, keratan sulfate, and glycopeptides, and the enzyme is absent or reduced in GM1-gangliosidosis and Morquio B patients. Morquio B patients show reduced catalytic activity for keratan sulfate and oligosaccharides but normal activity for ganglioside GM1. Ganglioside GM1 is mainly stored in neuronal tissue, while keratan sulfate mainly accumulates in cartilage. GM1-gangliosidosis has been classified into three major clinical forms according to age of onset and severity of symptoms: type I (infantile), type II (late infantile/juvenile) and type III (adult) [Suzuki et al., 2001]. Type I is the most severe and is associated with developmental arrest observed within 3 to 6 months of birth, macular cherry-red spots, skeletal dysplasia and death usually within the first two years of life.

Morquio B disease or mucopolysaccharidosis type IVB (MPS IVB) is characterized by progressive, generalized skeletal dysplasia without central nervous system involvement and no clinical signs of storage disease in neuronal tissues.

More than 50 disease-causing mutations and several polymorphisms have been described in the GLB1 gene. There are very few mutational studies in specific populations, such as those of patients from Italy [Caciotti et al., 2003; Morrone et al., 2000] or Brazil [Silva et al., 1999]. Furthermore, less than 30 Morquio B patients worldwide have been characterized for their DNA mutations [Bagshaw et al., 2002; Paschke et al., 2001]. Diagnostic sequencing analysis of the GLB1 gene coding region is available for GM1 patients and their at-risk relatives on a clinical basis.

For questions about testing for GM1, call EGL Genetics at (470) 378-2200 or (855) 831-7447. For further clinical information about lysosomal storage diseases, including management and treatment, call the Emory Lysosomal Storage Disease Center at (404) 778-8565 or (800) 200-1524.

1. Silva CM, et al. 1999. Six novel beta-galactosidase gene mutations in Brazilian patients with GM1-gangliosidosis. Hum Mutat 13:401-9.
2. Santamaria R et al. Twenty-one novel mutations in the GLB1 gene identified in a large group of GM1-gangliosidosis and Morquio B patients: possible common origin for the prevalent p.R59H mutation among gypsies. Hum Mutat. 2006 Oct; 27(10):1060.

Genes (1)



  • Confirmation of clinical diagnosis of GM1.
  • Prenatal testing for known familial mutation(s).
  • Assessment of carriers in high risk family members - known mutation analysis.


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. Array CGH will not detect point mutations or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
  • Mucopolysaccharide screen (urine GAG) (GA)
  • Lysosomal Enzyme Screening Panel (LS)
  • Known mutation analysis (Custom Diagnostics) is available to test family members.
  • Prenatal testing is available for known familial mutations only. Please call the Laboratory Genetic Counselor for specific requirements for prenatal testing before collecting a fetal sample.

How to Order

Requisition Forms