Case report: rapid-onset dystonia-parkinsonism related to a pathogenic ATP1A3 variant

*Correspondence: [e-mail].

Abstract

Case Presentation: A previously healthy 6-year-old child presented with fever, somnolence and gait impairment. Parents sought medical attention and, due to the symptoms suggestive of infection of the central nervous system (CNS), antibiotic and antiviral therapy was performed. Within a few hours, the patient developed flaccid tetraparesis, dysphagia and motor aphasia. There was no initial improvement with antibiotics, so an immunoglobulin cycle was prescribed, with a slight improvement of symptoms. After three months, the child developed dystonic movements, especially in the face, neck and upper limbs, and chorea. She was then referred to our clinic. Infectious screening was negative, electroneuromyography and electroencephalogram were normal. Movement disorders multigenic panel showed a heterozygous variant in the ATP1A3 gene - chr19:41,970,540 G >A, compatible with rapid-onset dystonia-parkinsonism (RPD). She also developed depressive symptoms, dysarthria and learning disabilities. Currently in outpatient follow-up, using levodopa, showing a partial favorable clinical response, with progressive motor improvement, becoming more independent in daily tasks.

Discussion: ATP1A3-related disorders are rare and have a broad phenotype. One of the classical presentations is RDP. It is an autosomal dominant disorder, with variable penetrance. De novo variants account for 50% of the cases. Its onset is usually in the first two decades of life and preceded by a trigger that can be infectious, psychological, head trauma, exercise, among others. Symptoms start abruptly, with bulbar symptoms, such as dysphagia and dysarthria, cranio-cervical dystonia, mild limb dystonia and bradikinesia. Cognitive impairment, executive function decline and psychiatric symptoms are also part of the disorder. Generally, this condition is not responsive to levodopa. However, our patient showed a partial favorable response, helping her regain motor abilities and walking independently again. Clinical presentation can differ in patients with the same pathogenic variants, even if they are related.

Final Comments: ATP1A3-related disorders have phenotypic heterogeneity, with a broad spectrum of clinical manifestations. Clinicians should be alert to this feature in order to identify patients with a suspicious phenotype to make the diagnosis, provide genetic counseling and proper clinical management.

Publication History

Article published online:
12 May 2025