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Título

Late-onset atypical parkinsonism and motor neuronopathy related to POLG gene variant

RESUMO

Case report
A 60-year-old patient presented with a 4-year-history of stiffness and slowing of the left upper limb, and shortly afterwards in the left leg. He also developed neck stiffness, urinary retention, and weight loss of 10kgs. The patient had no sleep complaints, REM sleep behavior disorder, cognitive complaints, or anosmia. Divergent strabismus in the right eye was present since childhood.
Neurological examination showed dysarthria, exotropia of the right eye, and facial hypomimia. Asymmetric bradykinesia more pronounced on the left side. Festinating gait with significant postural instability and camptocormia without ataxia.
Treatment was initiated with levodopa 1000mg and pramipexole 1.5mg daily with partial clinical response and wearing off after 1h30min. Cranial CT disclosed punctiform calcification of the basal ganglia. Brain and spinal cord MRI showed marked calcification in the basal ganglia. DaT-SPECT showed asymmetric reception of the radiotracer right less than the left side. Electrodiagnostic studies showed chronic preganglionic involvement in C6-T1 bilaterally and L4-S1 bilaterally. NGS-based gene panel testing was performed, showing the heterozygous variant c.678G>C (p.Gln226His) in the POLG gene.
Discussion
The human Polymerase Gamma (POLG) gene encodes the mitochondrial DNA polymerase responsible for replication and repair of the mitochondrial DNA. In adults, the most common movement disorder is parkinsonism, occurring in up to 43% of the patients. POLG-related parkinsonism has an earlier age of onset, at about 40 years and is initially asymmetric clinically and in imaging.
Tang et al. described Q226H POLG variant as potentially pathogenic. Different from what is seen in the literature our patient had a late-onset parkinsonism and poor response to levodopa. Nevertheless, our patient had early postural instability and camptocormia, that can be the presenting sign in patients with POLG variant, sphincter dysfunction, asymmetric DAT-SPECT findings, and neuronopathy on electrodiagnostic studies. These findings led to the differential diagnosis of a genetic metabolic cause for parkinsonism, and the diagnosis of POLG-related disorder was made.
Final remarks
Our case further expands our knowledge regarding POLG gene variants and phenotypes, as a highly heterogeneous spectrum, and shows the importance considering it in patients with parkinsonism.

Palavras Chave

POLG Parkinsonism

Área

Neurogenética