GLB1-related conditions including GM1-gangliosidosis and mucopolysaccharidosis type IVB (MPSIVB) are two distinct lysosomal storage disorders caused by mutations the GLB1 gene. This leads to a build up of GM1 gangliosides which causes the destruction of certain cells in many organs, particularly those in the brain. There is a wide range of severity for this disorder, however most individuals tend to be severely affected.
GM1-Gangliosidosis:
- Types: Divided into three subtypes based on age of onset and severity.
- Type I (Infantile form): Most common type. Infants show developmental delay, regression of milestones, cherry-red spot in the eye, skeletal issues, enlarged liver and spleen, and corneal clouding. Rapid progression leads to blindness and deafness by age one, with death often occurring before age three.
- Type II (Late-Infantile & Juvenile forms): Onset between one to ten years. Features include motor and cognitive delay, brain atrophy, potential cardiac problems, and corneal clouding. Life expectancy varies, with late-infantile form surviving up to 10 years, while some in the juvenile form may live into early adulthood.
- Type III (Adult form): Mild subtype with symptoms appearing in adulthood, including abnormal movements, speech difficulties, heart disease, brain atrophy, and skeletal issues. Lifespan varies.
MPS IVB (Mucopolysaccharidosis Type IVB):
- Features: Autosomal recessive disorder causing short stature, skeletal dysplasia, kyphoscoliosis, pectus carinatum, and “knocked-knees.” Corneal clouding and cardiac disease can occur. Intellectual abilities are typically normal.
- Severity: Onset in early childhood or adolescence; severe forms show symptoms between one to three years.
Management:
- GM1-Gangliosidosis: No cure; management focuses on improving quality of life. Therapies include physical, occupational, and speech therapy. Specialized strollers or wheelchairs might be necessary. Hydration, nutrition, and seizure management are crucial. Heart disease symptoms are treated.
- MPS IVB: No cure or specific treatment; management includes physical and occupational therapies. Regular monitoring by specialists (pulmonologists, audiologists, ophthalmologists, cardiologists) is essential.
This group of conditions is caused by pathogenic (disease-causing) variants in the GLB1 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
Resources:
Revised October 2023
