PINK1 Type of Young-Onset Parkinson Disease

Clinical characteristics: PINK1 type of young-onset Parkinson disease is characterized by early onset (mean age 33 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 suspected in individuals with early-onset parkinsonism (age <40 years), particularly if autosomal recessive inheritance is suggested by the family history. The diagnosis of PINK1 type of young-onset Parkinson disease is established by identification of biallelic PINK1 pathogenic variants on molecular genetic testing.

Management: Treatment of manifestations: This disorder usually responds well to L-dopa and other dopaminergic therapies. L-dopa-induced dyskinesias can be reduced by adjusting dopaminergic therapies and by adding antidyskinetic agents. Motor fluctuations can be ameliorated by dose fractionation and by adding COMT inhibitors. As in individuals with idiopathic Parkinson disease, deep brain stimulation should be considered in more advanced cases.

Prevention of secondary complications: L-dopa dosage should not exceed the level required for satisfactory clinical response. If not contraindicated, dopamine agonists should be employed to possibly delay the onset of motor fluctuations, as affected individuals often require several decades of treatment.

Surveillance: Neurologic follow up including assessment of treatment effectiveness every three to 12 months.

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. At conception, each sib of a proband has a 25% chance of being affected, a 50% chance of being a carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both pathogenic variants have been identified in an affected family member.