J Clin Neurol.  2020 Jan;16(1):75-82. 10.3988/jcn.2020.16.1.75.

Clinical and Genetic Spectrum of ATP1A3-Related Disorders in a Korean Pediatric Population

• Kim WJ
• Shim YK
• Choi SA
• Kim SY
• Kim H
• Hwang H
• Choi J
• Kim KJ
• Chae JH
• Lim BC

• KMID: 2467787
• DOI: http://doi.org/10.3988/jcn.2020.16.1.75

Abstract

BACKGROUND AND PURPOSE
The aim of this study was to expand the understanding of the genotype-phenotype spectrum of ATP1A3-related disorders and to evaluate the therapeutic effect of a ketogenic diet in patients with alternating hemiplegia of childhood (AHC).
METHODS
The clinical information of 13 patients with ATP1A3 mutations was analyzed by performing retrospective chart reviews. Patients with the AHC phenotype who consented to ketogenic diet were included in the trial.
RESULTS
Ten patients presented with the clinical phenotype of AHC, two patients presented with rapid-onset dystonia parkinsonism, and one patient presented with cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss. Two novel mutations of the AHC phenotype were identified: p.Ile363Thr and p.Asn743Ser. The clinical phenotypes of three mutations differed from those in previous reports: p.Arg597Pro, p.Thr769Pro, and p.Arg756Cys. One of the two patients who started a ketogenic diet experienced seizure provocation and so immediate stopped consuming the diet, while the other patient continued the ketogenic diet for 1 year, but this produced no clear benefit such as reduction of paroxysmal symptoms.
CONCLUSIONS
Our study is the first case series of ATP1A3-related disorders to be described in Korea and which further expands the understanding of its genotype-phenotype spectrum. A ketogenic diet showed no clear benefit for the patients with AHC.

Keyword

ATP1A3; alternating hemiplegia of childhood; ketogenic diet

MeSH Terms

Cerebellar Ataxia
Diet
Dystonia
Foot Deformities
Hearing Loss, Sensorineural
Hemiplegia
Humans
Ketogenic Diet
Korea
Optic Atrophy
Parkinsonian Disorders
Phenotype
Retrospective Studies
Seizures

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