Longitudinal Natural History Protocol for PRKN- and PINK1-Linked PD

• INCLUSION CRITERIA:

To be eligible to participate in this study, an individual must meet all of the following criteria:

All participants:

• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female between the ages of 18-80 years old
• Ability of subject to understand and the willingness to sign an informed consent document
• Ability of subject to travel to the NIH Clinical Center

Additional inclusion criteria for each cohort as below:

PD Mito Biallelic:

• Established clinical diagnosis of Parkinson s disease
• Two Pathogenic or likely pathogenic variants in PRKN or PINK1

PD Mito Monoallelic:

• Established clinical diagnosis of Parkinson s disease
• One Pathogenic or likely pathogenic variant in PRKN and/or PINK1

Idiopathic Parkinson s Disease (PD):

• Established clinical diagnosis of Parkinson s disease
• Etiology of PD is idiopathic/sporadic based on investigator determination

Non-manifesting mito:

• One or two pathogenic or likely pathogenic variant in PRKN and/or PINK1
• Lack of clinical diagnosis of Parkinson s disease
• Lack of current or clinically significant neurological disorder (based on investigator determination)

Healthy Volunteer

-Lack of current or clinically significant neurological disorder (based on investigator determination)

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

All participants:

• Symptomatic PD syndromes due to drugs (e.g., metoclopramide, flunarizine, neuroleptics), metabolic disorders (e.g., Wilson s disease hypothyroidism), encephalitis, brain lesion, atypical parkinsonism, other monogenic forms of PD (e.g., GBA1, LRRK2, SNCA, VPS35, CHCHD2, DJ1, ATP13A2) other genetic disorders that may cause parkinsonism (e.g., spinocerebellar ataxia, X-linked dystonia parkinsonism)
• Pregnancy at time of study enrollment
• Any other reason that, in the opinion of the investigator, would render the participant unsuitable for study enrollment
• Unwilling to allow samples or data to be shared with other researchers or institutions.
• NIH staff or family members of study team members

Healthy Volunteer:

-Participants who become pregnant during the study will be withdrawn from further study procedures at the time pregnancy is identified.

Procedural Exclusions:

Subjects may still be enrolled if they cannot participate in certain procedures due to not meeting the inclusion requirements for that specific procedure. Subjects who meet exclusion criteria for procedures listed below may still undergo the procedure at a later time if the reason of exclusion is no longer present.

Brain MRI:

• Contraindications to MRI such as a contraindicated non-removable metal device (i.e., pacemaker, defibrillator, insulin pump, metal clips, non-removable jewelry)
• Pregnancy

Accelerometer:

-Non ambulatory

Lumbar puncture procedure:

• PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
• INR greater than 1.4, thrombocytopenia (<70,000), or abnormal bleeding time or platelet dysfunction
• History of a bleeding disorder
• Use of anticoagulants or antiplatelets
• Pregnancy
• History of headache requiring blood patch after a previous LP

Needle muscle biopsy:

• PT/PTT values that are prolonged greater than or equal to 3 seconds from the upper limit of normal (including treatment with oral and parenteral anticoagulants)
• INR greater than 1.4, thrombocytopenia (<70,000), or abnormal bleeding time or platelet dysfunction
• History of a bleeding disorder
• Use of anticoagulants or antiplatelets
• Pregnancy