Category: Genetics (Non-PD)
Objective: We describe a case of fever-induced paroxysmal weakness and encephalopathy (FIPWE), also known as relapsing encephalopathy with cerebellar ataxia (RECA) and expand the phenotypic spectrum of ATP1A3 gene mutations.1,2
Background: ATP1A3 encodes the alpha-3-catalytic subunit of the Na+K+-ATPase transmembrane ion pump which is selectively expressed in neurons, particularly in the cerebellum and basal ganglia. Mutations in ATP1A3 have been described to cause three distinct phenotypes: alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss syndrome (CAPOS).3 However, as more patients with ATP1A3-related disorders are identified, a growing number of overlapping or intermediate syndromes have emerged. Several case reports describe a potential new distinct phenotype associated with different pathogenic variants at the amino acid residue p.Arg756. These individuals have recurrent neurological decompensation triggered by fever and can develop encephalopathy, hypotonia, weakness, ataxia, dystonia, or choreoathetosis.4
Method: Case study
Results: This 12-year-old boy presented to our movement disorders clinic with a history of two episodes of acute neurological decompensation with partial recovery in the setting of febrile viral illnesses at 4 and 9 years of age. With each episode he rapidly deteriorated and developed ataxia, dysarthria, hypotonia, choreoathetosis, and generalized weakness with prominent bulbar involvement. He was diagnosed with post-infectious cerebellitis after the first attack and a presumed metabolic or mitochondrial disorder after the second one. At the time of presentation to our clinic he had mild dysarthria, generalized dystonia worse on the right, and gait ataxia. Our evaluation found a heterozygous pathogenic variant in the ATP1A3 gene at c.2266C>T (p.Arg756Cys).
Conclusion: Our patient shares a similar clinical course and symptoms with previously reported cases of ATP1A3 mutations at residue p.Arg756. This case extends the clinical spectrum of ATP1A3-associated disorders by providing addition support for the phenotype-genotype correlation of p.Arg756 mutations. The phenotypic spectrum of ATP1A3-related disorders is still evolving. As the spectrum expands, it is important that clinicians be aware of the diverse presentations to reduce unnecessary treatments, tests, and misdiagnoses.
References: 1. Yano ST, Silver K, Young R, et al. Fever-Induced Paroxysmal Weakness and Encephalopathy, a New Phenotype of ATP1A3 Mutation. Pediatric Neurology. 2017;73:101-5. 2. Dard R, Mignot C, Durr A, et al. Relapsing encephalopathy with cerebellar ataxia related to an ATP1A3 mutation. Dev Med & Child Neurology. 2015;57:1183-6. 3. Brashear A, Sweadner SJ, Cook JF, et al. ATP1A3-Related Neurologic Disorders. 2008 Feb 7 [Updated 2018 Feb 22]. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993-2020. 4. Sabouraud P, Riquet A, Apitz M-A, et al. Relapsing encephalopathy with cerebellar ataxia are caused by variants involving p.Arg756 in ATP1A3. Eur J Paediatr Neurol. 2019;23(3):448-455.
To cite this abstract in AMA style:D. Ferman, Q. Luc. A Child with Fever-Induced Paroxysmal Weakness and Encephalopathy with ATP1A3 mutation [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/a-child-with-fever-induced-paroxysmal-weakness-and-encephalopathy-with-atp1a3-mutation/. Accessed December 5, 2023.
« Back to MDS Virtual Congress 2021
MDS Abstracts - https://www.mdsabstracts.org/abstract/a-child-with-fever-induced-paroxysmal-weakness-and-encephalopathy-with-atp1a3-mutation/