Pathogenic variants in the GLB1 gene can result in two different disorders called GM1 gangliosidosis and mucopolysaccharidosis type IVb. Both diseases have severe and mild forms. Type 1 GM1 gangliosidosis presents in infancy and is characterized by developmental delay and regression, progressive rigidity and spasticity, cardiomyopathy, and loss of vision and hearing. Life expectancy is 2 to 3 years. Type 2 GM1 gangliosidosis (late-infantile form) has an age of onset during toddlerhood and progresses more slowly than type 1. Death usually occurs by age 10. Type 2 GM1 gangliosidosis (juvenile form) begins between ages 3 and 10, and is characterized by a plateau and then loss of previously attained motor and cognitive skills. Type 3 GM1 gangliosidosis has an age of onset during adulthood and resembles Parkinson disease with symptoms including an unsteady gait and cardiomyopathy. Mucopolysaccharidosis Type IVb is often diagnosed between ages 1 and 3 and involves severe skeletal abnormalities, cardiomyopathy and respiratory problems. Intellect is not usually affected. A later-onset form also exists, where symptoms do not begin until later in childhood. Life expectancy is dependent upon the severity of the disease and may vary from childhood to adulthood. Depending on the variants inherited by the patient, it may be possible to predict whether the development of GM1 gangliosidosis or mucopolysaccharidosis type IVb is more likely, but it is not currently possible to predict the severity of the disease.
For information about carrier frequency and residual risk, please see the residual risk table.