Clinical characteristics: PINK1 type of young-onset Parkinson disease is characterized by early onset (median age at onset 32 years) of tremor, bradykinesia, and rigidity that are often indistinguishable from other causes of Parkinson disease. Lower-limb dystonia may be a presenting sign. Postural instability, hyperreflexia, abnormal behavior, and psychiatric manifestations have been described. The disease is usually slowly progressive. Individuals have a marked and sustained response to oral administration of levodopa (L-dopa), frequently associated with L-dopa-induced fluctuations and dyskinesias.

Diagnosis/testing: The diagnosis of PINK1 type of young-onset Parkinson disease is established by the identification of biallelic PINK1 pathogenic variants on molecular genetic testing.

Management: Treatment of manifestations: PINK1 type of young-onset Parkinson disease usually responds well to L-dopa and/or other dopamine agonists, which may be used in combination with catechol-O-methyltransferase inhibitors or monoamine oxidase-B inhibitors, anticholinergics, and amantadine. Physical therapy and/or occupational therapy to improve and/or maintain gross motor and fine motor skills as well as speech therapy. Invasive therapies include intrajejunal L-dopa-carbidopa pump, subcutaneous apomorphine pump, or deep brain stimulation. L-dopa-induced dyskinesias can be treated by reducing L-dopa dose, switching to dopamine receptor agonists, deep brain stimulation, or continuous treatment with L-dopa or apomorphine. Atypical neuroleptic agents can be used for neuropsychiatric manifestations; standard treatments for depression. Cholinesterase inhibitors can be used to treat dementia. Consider droxidopa, midodrine, fludrocortisone, and/or supportive measures for orthostasis. Symptomatic treatment for constipation.

Surveillance: Neurologic evaluation every three to 12 months to assess motor and non-motor manifestations and treatment efficacy; in addition, assess for atypical manifestations and therapy needs at each visit. Neuropsychiatric evaluation in those with mood disorder / psychotic symptoms or as needed. Cognitive assessment annually or as needed. At each visit, assess nutrition and safety of feeding; assess for symptoms of orthostasis and measure supine and standing blood pressure and pulse; assess for constipation, urinary urgency, or urge incontinence; and assess family needs.

Agents/circumstances to avoid: Neuroleptic treatment may exacerbate parkinsonism.

Genetic counseling: PINK1 type of young-onset Parkinson disease is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a PINK1 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being heterozygous, and a 25% chance of inheriting neither of the familial PINK1 pathogenic variants. Once the PINK1 pathogenic variants have been identified in an affected family member, heterozygote testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.