Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients

Natural History Study of Infantile and Juvenile GM1 Gangliosidosis (GM1) Patients

Owing to the rarity, severity, speed of progression and fatal prognosis of infantile and juvenile GM1, there is a limited understanding of overall disease progression and meaningful outcome measures. This study aims to build a natural history data set through collection of a number of clinical, imaging, and laboratory assessments that may be specific predictors of GM1 disease progression and clinical outcome. Having a GM1 natural history data set can inform potential efficacy endpoints and biomarkers for future clinical trials.

This natural history study will follow up to 40 subjects diagnosed with GM1 gangliosidosis (up to 20 infantile (Type 1) and 20 late infantile/juvenile (Type 2)) for up to 3 years. Visits will be conducted every 6 months, during which several procedures will be performed and the data recorded in order to learn about the natural course of the disease, including changes in clinical and neurological assessments and electrophysiologic, imaging and biofluid biomarkers. Study procedures include: physical & neurological exam, blood & urine sample collection, questionnaires & assessments of development, seizure diary, ECHO, ECG, x-ray and ultrasound (if MRI not performed), EEG and genetic testing (if not already done).

The following procedures are subject to local/institutional policies and the medical discretion of the Study Physician: MRI, lumbar puncture (spinal tap) and General anesthesia/sedation (for MRI and LP).

Inclusion Criteria:

1. Documentation/ Confirmation of reduced beta-galactosidase enzyme activity in leukocytes
2. Confirmed diagnosis of infantile or juvenile GM1 gangliosidosis with documentation of GLB1 mutations
3. Parent/Caregiver capable of providing informed consent (if cognitively able, child to provide assent as well)
4. Infantile (Type 1) GM1 subjects: Documented symptom onset by 6 months of age with significant hypotonia on exam or history elicited from parent(s)/ caregiver(s)
5. Juvenile (Type 2) GM1 subjects: Documented symptom onset after 6 months of age OR documented symptom onset prior to 6 months of age without significant hypotonia on exam or elicited from parent(s)/ caregiver(s)

Exclusion Criteria:

1. Enrollment in any other clinical study with an investigational product/ therapy (patients receiving miglustat off-label will be eligible)
2. Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or a secondary cause that may, in the opinion of the investigator, confound interpretation of study results
3. Any condition that, in the opinion of the investigator, would put the subject at undue risk or make it unsafe for the subject to participate