Objective: We present a rare familial case of a patient with ATP1A3 dystonia parkinsonism, which improved with levodopa.

Background: Rapid onset dystonia parkinsonism can be secondary  to ATP1A3 gene mutation spectrum disorders. The phenotypical presentation of ATP1A3 mutations may be broad even within families, and includes childhood learning disabilities, seizures, and alternating hemiplegia of childhood (1).

Method: 45-year-old right-handed man developed progressive left-sided weakness over several years, causing difficulty in using his left hand with left hand and arm stiffness, and occasional left foot dragging.  His 4-year-old son has developmental delay and seizures, and was found on genetic epilepsy panel to have an ATP1A3 autosomal dominant heterozygous c.2015C>A pathogenic variant.

Results: Examination showed mild left arm greater than leg spastic hemiparesis, with  mild left arm drift, especially affecting the hands and fingers; moderate to severe left arm fix on arm roll testing, and  left bradykinesia.  There was dystonic posturing of his left hand, but the muscle tone was normal.  Gait exam showed mildly diminished left arm movement with a cortical thumb.  Reflexes were slightly brisker in the left arm and leg, with flexor responses on plantar testing. MRI brain was normal. Next generation sequencing for ATP1A3 revealed a heterozygous c.2015C>A pathogenic variant.  Carbidopa/levodopa 25/100 daily improved his left hand and arm stiffness but caused adverse effects. Extended release carbidopa/levodopa 35/140 daily improved his left hand stiffness and function.

Conclusion: This case illustrates the importance of attention to family history of neurological disease.  The diagnosis of ATP1A3 related disorders can be challenging due to varied phenotypic presentations, even within the same family. Our case also demonstrates that levodopa can be an effective treatment for dystonia parkinsonism associated with ATP1A3 related disorders. 

References: 1. Heinzen, E.L.,et. al., Lancet Neurol. 2014 May; 13(5): 503–514. doi:10.1016/S1474-4422(14)70011-0. https://pmc.ncbi.nlm.nih.gov/articles/PMC4238309/

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MDS Abstracts - https://www.mdsabstracts.org/abstract/dopamine-responsive-atp1a3-dystonia-parkinsonism-a-case-report/