Objective: To study the clinical phenotype of all patients with ATP 1A3 mutation in the genetic study

Background: ATP1A3 is associated with a broad spectrum of neurologic disorders, which continues to expand beyond the initial phenotypes of alternating hemiplegia of childhood, rapid-onset dystonia-parkinsonism, and CAPOS. Other manifestations described are childhood-onset schizophrenia, epileptic encephalopathy, cerebellar ataxia, areflexia, optic atrophy and sensorineural hearing loss, childhood rapid onset ataxia, relapsing encephalopathy.

Method: All patients suspected to have the clinical manifestation fitting into ATP1A3 spectrum and whose genetic studies confirming mutations in the ATP1A3 gene were included in the study Detailed clinical history,examination ,imaging findings and other routine investigations were studied

Results: HSP-like presentation of ATP1A3- A 26-year-old lady presented with 12 years history of febrile illness followed by oromandibular dystonia and spasticity with good response to levodopa. MRI Brain revealed mild thinning of the corpus callosum with the ear of lynx sign.Likely pathogenic mutation was detected in the ATP1A3 gene.Early onset PD with Levodopa responsiveness-A 54-years-old lady with 9 years of PD with levodopa responsiveness . Likely pathogenic mutation was detected in ATP1A3 gene. CAPOS-like presentation of ATP1A3- A 9 year old girl with 6 years history of abnormal eye movements,reduced vision,gait ataxia.WES suggestive of ATP1A3 gene missense mutation. RECA Phenotype- 11-year-old female with illness of 8 years- febrile encephalopathy, cognition and motor milestones regression,epilepsy and oromandibular dystonia.WES suggestive of ATP1A3 gene missense mutation.

Conclusion: The spectrum of manifestations secondary to ATP1A3 mutations is expanding given the current increasing availability of gene panel and whole exome sequencing testing and the increasing awareness of the phenotypes caused by such mutations. The phenotype is still expanding.We report a complicated HSP like presentation of ATP1A3 with good levodopa responsiveness  and EOPD with excellent levodopa responsiveness which have not been described previously

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MDS Abstracts - https://www.mdsabstracts.org/abstract/diverse-clinical-phenotypes-of-atp1a3-mutations-a-case-series-of-four-patients/