The portal for rare diseases and orphan drugs

Prevalence of LOPD is unknown. The prevalence of PD is estimated at about 1% in people over 60 years of age in the general population in Europe and only 10% of the reported PD has shown to be hereditary.

Onset of LOPD is > 50 years with predominant symptoms including tremor at rest (70% of cases), gait complaints and falls (20%), bradykinesia (20%), rigidity and painful cramps (8%). Compared to young onset PD (YOPD; see this term), a higher risk of developing gait freezing and falls but a lower risk of developing dystonia, dyskinesia and LID have been reported. Patients with hereditary LOPD are also more affected by severe diplopia, cognitive impairment, and gastrointestinal and urinary disorders. LOPD patients report a lower prevalence of non-motor symptoms such as depression, hallucinations, behavioral disturbances (i.e. agitation or impulse control disorder), dementia and apathy.

The exact etiology of hereditary LOPD is still unknown but mutations in the genes SNCA (4q21.3-q22), LRRK2 (12q12), and VPS35 (16q12) have been implicated in its pathogenesis. Heterozygous mutations in GBA (1p22; glucocerebrosidase) are the most common risk factor for PD.

Transmission is autosomal dominant. Genetic counseling should be offered to the affected families informing them of the 50% risk the offspring has of inheriting the disease-causing mutation and therefore being affected with the disorder.