TABLE.
Parkinsonism in PPP2R5D (NM_006245.3) p.E200K Mutation Carriers: Clinical Features
| Characteristic | Case 1 | Case 2 | Case 3 |
|---|---|---|---|
| Ancestry | European | European | European |
| Sex | Male | Male | Female |
| Age at last visit | 61 years | 34 years | 44 years |
| Genetic test | Exome sequencing | Exome sequencing | Exome sequencing |
| Developmental history | Term birth. Motor delay: walked at 2–3 years. Language delayed. Mild intellectual disability: special education classes; graduated from vocational high school | Term birth: possible amniotic fluid aspiration. No motor delay. Language delayed. Severe learning disability: stopped schooling at 15 years | Term birth. Motor delay: sat at 9–10 months; cruised at 2 years. I Iypotonia. Language delayed. Mild intellectual disability |
| Seizures | No | No | No |
| Past medical history | Diabetes mellitus type 2, hypertension, sensorimotor neuropathy | None | Overgrowth (height 97th percentile by 2.5 years; macrocephaly) |
| Parkinsonism: age at onset | 40 years | 27 years | 22 years |
| Motor features | Onset of gait difficulty, generalized hradykinesia; subsequent freezing of gait. Atrcmulous | Onset of right arm rest tremor; subsequently, predominantly akinetic–rigid. Postural instability | Onset of asymmetric rest tremor; subsequent freezing of gait, postural instability, cervical dystonia |
| Nonmotor features | Autonomic: non motor off symptoms (sweats, urinary urgency). No cognitive decline | Autonomic: constipation, urinary urgency. Rapid eye movement sleep behavior disorder. Depression, anxiety. Early cognitive decline | Autonomic: none. Sleep disturbance: none. Visual hallucinations |
| Atypical features | None | Myoclonus; oculomotor abnormalities | None |
| Rate of progression | Fluctuations: 9 years after onset. Freezing of gait: 10 years after onset. Wheelchair bound: 17 years after onset | Fluctuations: 3 years after onset. Postural instability: 5 years after onset. Remains ambulatory without aids | Slow progression since onset (neady 20 years) |
| Diagnostic studies | Magnetic resonance imaging of brain without contrast: subcortical white matter T2 hyperintensities(Fig 1A) | Dopamine transporter imaging scan: abnormal. Magnetic resonance imaging of brain without contrast: normal (Fig 1B). Electromyography/Nerve conduction study: normal | None |
| Levodopa and other treatment response | Levodopa responsive. Deep brain stimulation (subthalamic nuclei, 17 years after onset): unclear benefit | Levodopa responsive | Levodopa responsive |
| Complications of therapy | Motor and nonmotor off symptoms. Impulse control disorders (gambling, overeating) with dopamine agonist | Motor and nonmotor off symptoms. Impulse control disorders (gambling, hypersexuality) with dopamine agonist | Fluctuations: motor off symptoms (marked rigidity); dopamine-induced dyskinesias |
| Agc/causc of death | 61 years/aspiration pneumonia | Not applicable | Not applicable |