Young adult onset parkinsonism disease (YOPD) groups together all forms of Parkinsonism manifesting before 50 years of age. The cause, clinical presentation, clinical course and management of the early-onset forms differ from those of the classic form of the disease, which generally becomes apparent after 60 years of age. Incidence of YOPD has been estimated at 1.5/100 000 individuals between 30 and 50 years of age. In addition to rigidity, resting tremor, akinesis and asymmetry, YOPD is characterised by dystonic posture (often the first sign of the disease, predominantly affecting the lower limbs); sharp reactions; a high frequency of bradykinesia; trembling and rigidity; a good response to anti-Parkinson treatment; absence of cognitive defects and axial involvement; higher frequency and earlier onset of motor fluctuations and dyskinesis; increased frequency of mood swings and disturbances affecting family and professional life and slower clinical progression. Several forms of YOPD have been identified. Autosomal recessive forms with earlier onset are caused by mutations in the parkin (PARK2), DJ-1 (PARK6) and Pink1 (PARK7) genes. In the European population, mutations in the parkin gene are responsible for more than 50% of familial YOPD cases. The frequency of the PINK1 and DJ-1 mutations is much lower. Mutations in the LRRK2 gene, encoding dardarin, may be responsible for sporadic or dominantly inherited familial forms of the disease. Diagnosis is made by analysis of the clinical signs of the disease and is confirmed by genetic analysis and cerebral scintigraphy of the dopamine transporters. Differential diagnosis should consider a diverse range of diseases including the L-Dopa-sensitive dystonias, Wilson disease, Gaucher disease type 3, pantothenate kinase-associated neurodegeneration and the juvenile forms of Huntington disease or Dento-Rubro-Pallido-Luysian atrophy, and central basal ganglia lesions. These diseases may manifest as a form of Parkinson's diseasebut are usually associated with neurological signs or morphological cerebral anomalies. Genetic counselling is recommended for familial forms and/or if screening for specific mutations is indicated. However, counselling remains controversial as the disease is debilitating but non-lethal and effective treatments are available. In addition, the penetrance of the various causative mutations has not yet been established. Treatment is targeted towards combating the symptoms linked to dopaminergenic denervation, delaying the appearance of and treating the later complications associated with the treatment (motor fluctuations and dyskinesis) and managing the symptoms not responding to dopaminergenic treatment. The initial recommended treatment is monotherapy with dopaminergenic agonists. Non-ergot derivatives (peribidil, ropinirole, pramipexole, rotigotine) should be administered in preference to ergot derivatives (bromocriptine, lisuride, pergolide) as a result of the small risk of cardiopulmonary and retroperitoneal fibrosis. Relatively early introduction of L-Dopa, which is often effective against the motor symptoms of the disease, should be discussed together with the possibility of minimising the risk of fluctuations in the effectiveness of the therapy by administration of catechol-O-methyl-transferase (COMT) inhibitors (entacapone, tolcapone). In the later stages of the disease, subtle adaptation of the drugs comprising the polytherapy should allow the therapeutic equilibrium to be maintained. Treatment should be accompanied by professional, personal and familial management of patients. When the pharmacological approach is no longer sufficient to allow a good quality of life, a surgical approach involving bilateral stimulation of the subthalamic ganglion, may be discussed.
Last update: May 2006