Levodopa‐Responsive Parkinsonism with Prominent Freezing and Abnormal Dopamine Transporter Scan Associated with SANDO Syndrome

This 64-year-old male patient, with no past or family history of relevance, initially sought medical care at the age of 30 because of tingling and numbness of the lower extremities. This was found to be related to large-fiber sensory neuropathy. Symptoms gradually worsened over the ensuing years and affected his walking with evidence of sensory ataxia. However, he managed to walk unaided and carried on his employment. At the age of 40 years, he developed slurring of speech. When revaluated at the age of 55, he was found to have further signs with eye movement abnormalities compatible with external ophthalmoplegia. At the age of 57, he developed a rest tremor on his right hand. He had weakness of dorsiflexion of both his feet with a “foot drop,” but, at this stage, he also started to have abnormal posturing of his feet while walking. At the age of 60, his mobility worsened, leading to significant confinement and walking only with support of a frame. Owing to the presence of these new symptoms, he was referred to our department. Examination was suggestive of markedly restricted ocular movements with absent Bell’s phenomenon (external ophthalmoplegia). He had facial hypomimia with forehead wrinkling. Speech was dysarthric (see Video 1). Strength was normal in proximal and distal arm muscles, but there was weakness at both ankles. Reflexes were absent, with the exception of the right biceps jerk, whereas plantars were flexor. He had reduced pinprick sensation distally up to the knees bilaterally, as well as vibration sense to the costal margin on the right and iliac crest on the left. He also had a rest tremor of the right hand with reemergence on posture, along with bradykinesia on both fingerand foot-tapping tasks (right > left) and cog-wheeling rigidity on enforcement. He had mild finger-nose ataxia. His walking (with support) was slow and ataxic and he further had FOG, and he also had marked postural instability (see Video 1). Apart from his motor symptoms, he had constipation, but no other nonmotor features of Parkinson’s disease (PD). Neurophysiology confirmed a sensorimotor polyneuropathy with some denervation changes on electromyography. His MRI brain was normal, but dopamine transporter imaging (DaTscan) was abnormal, with reduced binding of tracer in the putamen bilaterally with relative sparing of the caudate nuclei (Fig. 1). Based on the SANDO phenotype, he and his mother (who was unaffected) were tested genetically for common POLG gene mutations. He was compound heterozygous for c.1399G>A (p.Ala467Thr) and c.2243G>C (p.Trp748Ser), the autosomalrecessive pathogenic variants. His mother was a carrier for the latter. He and his mother were also heterozygous for the common POLG c.3428A>G (p. Glul 143Gly) polymorphism. He was treated with L-dopa (300 mg/day), and Clinical Global Improvement (CGI) score was 2 (moderate clinical improvement). He has been on this L-dopa dosage for the last 2 years, without any dyskinesia or motor complications.