Objective: This is a case of a 51-year-old lady with POLR3A related leukodystrophy and secondary dopa responsive parkinsonism.

Background: Neurologic symptoms began 15 years ago with cognitive decline, with decreased verbal fluency and processing. She then developed left side tremor and rigidity. She was assessed by several movement disorder centers and diagnosed with parkinsonism. Her symptoms were clearly levodopa responsive, however she began suffering from severe motor fluctuations requiring increased levopdopa intake and addition of entacapone. Over the last 2 years she developed severe peak dose dyskinesias. Her current medications include sinemet 5 times daily, amantadine twice daily and pramipexole 3 times daily. She has a past medical history of PCOS, infertility and additional adult teeth requiring extraction. Family history is significant for Parkinson’s disease in her mother at age 70.

Method: Mental status exam is significant for executive dysfunction, inattention and impaired recall. Extrapyramidal exam in the “off” state reveals hypomimia, rigidity, rest tremor and bradykinesia on the left to a greater extent than the right. She exhibits bilateral heel-shin ataxia and dysdiadochokinesia. Gait is composed of decreased stride, decreased arm swing on left and occasional freezing. Repeat exam in the “on” state shows marked improvement in tremor, rigidity and bradykinesia with significant generalized dyskinesia, a 28 point improvement in UPDRS 3. Her investigative workup included an MRI brain demonstrating severe generalized leukodystrophy. She underwent whole exome analysis revealing compound heterozygous mutations on the POLR3A gene.

Results: Mutation of the POLR3A gene causes an autosomal recessive leukodystrophy, with various phenotypes including spasticity, ataxia, tremor, abnormal dentition and hypogonadotropic hypogonadism and central hypomyelination. Parkinsonism is an unusual manifestation of Pol III-related leukodystrophy. The patients mutations had not been previously described in this gene. The relationship between genotype and spectrum of phenotypes is still poorly defined. Many aspects of her history and exam are consistent with previously described clinical syndromes, with later onset than typical.

Conclusion: Given the severity of her motor fluctuations and dyskinesia these features are now her major source of disability and she is due to undergo deep brain stimulation surgery, the results of which will be presented.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/polr3a-leukodystrophy-presenting-with-levodopa-responsive-parkinsonism/