Diagnostic Criteria

GLB1-related disorders comprise two phenotypically unique disorders, GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB). Based on age of presentation, three types of GM1 gangliosidosis have been described: type I (infantile), type II (late infantile and juvenile) and type III (chronic/adult).

Suggestive Findings

A GLB1-related disorder is suspected in individuals with the following clinical, radiographic, neuroimaging, and laboratory findings and family history.

Clinical Findings

Type I (infantile; onset age 1 year) GM1 gangliosidosis should be suspected in infants with the following clinical findings:

Source: GeneReviews — "GLB1-Related Disorders"

Differential Diagnosis

GM1 Gangliosidosis Type I (infantile) GM1 gangliosidosis. See . Table 4. Genetic Disorders of Interest in the Differential Diagnosis of Type I (Infantile) GM1 Gangliosidosis

Management Guidelines

No clinical practice guidelines for GLB1-related disorders (GM1 gangliosidosis and MPS IVB) have been published. It is important to note that all GLB1-related disorders may be associated with anesthetic risks. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a GLB1-related disorder, the evaluations summarized in , , , and (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 7. Recommended Evaluations Following Initial Diagnosis in Individuals with Type I (Infantile) GM1 Gangliosidosis

Source: GeneReviews — "GLB1-Related Disorders"

Clinical Guidance

The following should be avoided:

• Unplanned anesthesia management. Because children with MPS IVB and those with GM1 gangliosidosis with skeletal involvement (spine anomalies, short neck, large head, and risk for atlantoaxial instability due to odontoid hypoplasia) are at increased risk for complications of anesthesia anesthesia is best done with advanced planning by experienced specialists whenever possible.

• Psychotropic medications. Because psychotropic medications have been associated with worsening neurologic disease in adults with Tay-Sachs disease (which is caused by deficiency of the second enzyme in the beta-galactosidase pathway) , use of these medications in individuals with a GLB1-related disorder should be avoided whenever possible.

• For individuals with type I (infantile) GM1 gangliosidosis

• Positioning that increases aspiration risk during feedings

• Seizure medication dosages that result in excessive sedation

• For individuals with types II and III (juvenile and adult) GM1 gangliosidosis. Circumstances that exacerbate fall risk

• For persons with MPS IVB. Excessive weight gain, which causes undue stress on the axial skeleton and may decrease the ability to ambulate independently. It is important that nutrition optimize growth while maintaining a lean habitus.

Source: GeneReviews — "GLB1-Related Disorders"

Surveillance Guidelines

Table 15. Recommended Surveillance for Individuals with GM1 Gangliosidosis

Source: GeneReviews — "GLB1-Related Disorders"