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Review
. 2021 Sep;9(9):e1772.
doi: 10.1002/mgg3.1772. Epub 2021 Aug 2.

Variants of ATP1A3 in residue 756 cause a separate phenotype of relapsing encephalopathy with cerebellar ataxia (RECA)-Report of two cases and literature review

Mateusz Biela  1 , Malgorzata Rydzanicz  2 , Krystyna Szymanska  3 , Karolina Pieniawska-Smiech  4 , Aleksandra Lewandowicz-Uszynska  5 , Joanna Chruszcz  6 , Lucyna Benben  7 , Malgorzata Kuzior-Plawiak  7 , Pawel Szyld  8 , Aleksandra Jakubiak  1 , Leszek Szenborn  6 , Rafal Ploski  2 , Robert Smigiel  1
Affiliations
Review

Variants of ATP1A3 in residue 756 cause a separate phenotype of relapsing encephalopathy with cerebellar ataxia (RECA)-Report of two cases and literature review

Mateusz Biela et al. Mol Genet Genomic Med. 2021 Sep.

Abstract

Background: Variants in ATP1A3 cause well-known phenotypes-alternating hemiplegia of childhood (AHC), rapid-onset dystonia-parkinsonism (RDP), cerebellar ataxia, areflexia, pes cavus, optic atrophy, sensorineural hearing loss (CAPOS), and severe early infantile epileptic encephalopathy. Recently, there has been growing evidence for genotype-phenotype correlations in the ATP1A3 variants, and a separate phenotype associated with variants in residue 756-two acronyms are proposed for the moment-FIPWE (fever-induced paroxysmal weakness and encephalopathy) and RECA (relapsing encephalopathy with cerebellar ataxia).

Materials and methods: Herein, we are describing two new pediatric cases with a p.Arg756His change in the ATP1A3 gene. Both patients have had more than one episode of a neurological decompensation triggered by fever with severe hypotonia and followed by ataxia. Thirty-three cases from literature were analyzed to define and strengthen the genotype-phenotype correlation of variants located in residue 756 (p.Arg756His, p.Arg756Cys, p.Arg756Leu).

Conclusions: Patients with a ATP1A3 variant in residue 756 are characterized by recurrent paroxysmal episodes of neurological decompensations triggered by fever, with severe hypotonia, ataxia, dysarthria, symptoms from the orofacial area (dysphagia, drooling) as well as with altered consciousness. Recovery is slow and usually not full with the persistent symptoms of cerebellar ataxia, dysarthria, dystonic and choreiform movements.

Keywords: ATP1A3; cerebellar ataxia; hypotonia; relapsing encephalopathy; whole-exome sequencing.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Results of molecular examination. Amplicon deep sequencing family study of ATP1A3 p.Arg756His variant. A – Patent 1 (P1), B – Patient 2 (P2). IGV screen shot is given oh the left hand side, while pedigree with genotype‐phenotype information is given on right: circle represents female, square indicates male, filled symbol ‐ affected individual. Proband is marked with black arrow. P ‐patient, M – mother, F – father, S – sister, wt – wild type genotype
FIGURE A1
FIGURE A1
Inclusion and exclusion criteria for review of patients with p.Arg756 ATP1A3 mutation
See this image and copyright information in PMC

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