ATP1A3-related disorders: case series from a referral center in São Paulo, Brazil

*Correspondence: [e-mail].

Abstract

Case Presentation: Case 1 A girl with a history of refractory seizures, motor delay and ataxic gait developed sudden dysarthria and dysphagia with 10 years old, followed by oromandibular and hand dystonia, worsening of gait and aggressive behavior. When she was 14 years old, during a febrile illness, she was admitted to the hospital with sudden tetraparesis with progressive spontaneous improvement. MRI showed discrete cerebellar atrophy and right mesial temporal sclerosis. Whole exome sequencing (WES) revealed a heterozygous missense pathogenic variant in the ATP1A3 gene (c.2155G>A; p.[Gly719Arg]). At present, the patient has daily episodes of ocular, oromandibular, trunk and limb dystonia. Case 2 A 1-month-old boy presented episodes of focal seizures. A few months later, he started to show monocular horizontal nystagmus and paroxysmal episodes of alternating hemiparesis and quadriparesis. Neurologic examination with 1 year old showed global developmental delay and hypotonia. Brain MRI was normal. WES was performed and found a heterozygous missense pathogenic variant in the ATP1A3 gene (c.2443G>A; p.[Glu815Lys). Case 3 A 5-month-old girl started episodes of dystonic postures of the limbs. She also showed global developmental delay and ataxia. Brain MRI was normal. WES showed a heterozygous missense pathogenic variant in the ATP1A3 gene (c.2839G>A; p.[Gly947Arg]). At present, she is 19 years old and has mild cognitive impairment and occasional episodes of sudden hemidystonia. Case 4 A 2-year-old girl with a history of seizures presented episodes of choreoathetosis. 1 year later, she started episodes of convergent strabismus and exotropia of the right eye. 7 months later, she had a sudden episode of hemiparesis with spontaneous improvement. At the age of 5 years old, she was hospitalized with worsening seizures during a febrile illness, developmental regression, choreoathetosis and dystonic postures of hands and feet. Brain MRI showed global cerebral atrophy. WES demonstrated a heterozygous missense likely pathogenic variant in the ATP1A3 gene (c.2225A>T; p.Asp742Val).

Discussion: ATP1A3-related disorders represent an expanding spectrum of clinical manifestations with 3 classical phenotypes: rapid-onset dystonia-parkinsonism, alternating hemiplegia of childhood (AHC) and CAPOS syndrome.

Final Comments: Here we described 2 typical cases of AHC (cases 2 and 3), 1 case of AHC with prominent chorea and important developmental regression (case 4) and 1 atypical case showing overlapping phenotype (case 1).

 

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Artikel online veröffentlicht:
12. Mai 2025