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

Background: Parkinson s disease is a neurologic disorder that affects movement. Its cause is unknown, and it usually begins later in life. Gene changes (PRKN and PINK1) can also cause rare types of Parkinson s disease that start at a young age. Researchers want to conduct a natural history study to learn more about how genes play a role in Parkinson s disease. Objective: To collect data and biological samples from people with different types of Parkinson s disease. Eligibility: People aged 18 to 80 years with either Parkinson s disease or PRKN- and PINK1-linked Parkinson s disease. Healthy volunteers are also needed. Design: Participants will have 6 clinic visits over 5 years. Each visit may take 1 to 3 days. During each visit: Participants will have a physical exam. The exam will be videotaped. They will answer questions about their movement, thinking, mood, and sense of smell. The extent of any symptoms of Parkinson s disease will be evaluated: Participants movements may be assessed with a finger tapping test. They may be asked to scratch and sniff different scented strips to identify odors. They will wear motion sensors on their arms, legs, chest, and back at the clinic. They will wear motion sensor devices on their wrists at home for 1 week. Blood and urine samples will be collected. Other tests are optional: Magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube. Lumbar puncture (spinal tap). A thin needle will be inserted into their lower back to draw out a sample of the fluid around their spinal cord. Muscle biopsy. A small sample of tissue will be taken from the leg.

* 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 (\