Genetic Studies of Lysosomal Storage Disorders

• INCLUSION/EXCLUSION CRITERIA:

For inclusion, the participant, of any age after birth, on initial screening must be found to have or be a carrier of a documented lysosomal storage disorder or be a family member of a documented proband. Healthy controls, > 18 years of age, will be recruited through the NIH healthy volunteer pool or we will invite unaffected spouses or relatives to participate. Healthy controls are necessary to determine the frequency of motor and non-motor symptoms in the general population. Parkinson disease patients, > 18 years of age, will be recruited from the Parkinson disease clinic at the NIH or by self-referral and will also be used for phenotypic comparison with GBA1-associated parkinsonism.

Individuals who, in the opinion of the Investigator, are unable to comply with the protocol or have medical or social conditions that would potentially increase the risk of participation will be excluded from enrolling in the study. There will be no exclusion based upon age, gender, ethnicity, socioeconomic status, or any other factor. Cognitively impaired individuals may be enrolled if the legal guardian or durable power of attorney (DPA) consents, and assent will be obtained, when appropriate because a significant portion of patients with neurodegenerative disorders may develop cognitive impairment and it is important to include this information in the clinical phenotype. Pregnant or nursing women will also be included because all evaluations and procedures in this protocol do not pose risk to the mother and the fetus as no radiation or imaging studies will be performed for research purpose. Pregnancy in patients with GD and other lysosomal storage disorders presents specific challenges with regards to skeletal, hematological, and possibly visceral complications throughout gestation. It is important to capture the natural history of the disease during pregnancy to assess benefits of initiation/continuation/discontinuation of therapy depending on clinical signs and symptoms. Information obtained from participation of this population is of great value for counseling, prevention of complications, and prognostic implications. Participants are free to refuse any evaluation without affecting participation in this protocol.

These are generally pan-ethnic disorders. Efforts will be made to include any patient from an under-represented minority with these disorders.

Family members eligible/recruited include adult obligate carrier relatives, parents and siblings of Gaucher disease probands, and/or any relative with and without parkinsonism, where noncarriers volunteer for participation to serve as controls.

Eligibility criteria for healthy and PD control group participants include healthy participants recruited from the Healthy volunteers office or healthy non-mutation carriers family members who voluntarily agree to participate. Patients with Parkinson disease who do not carry GBA1 mutations are eligible to participate to serve as controls