A novel ATP1A3 mutation with unique clinical presentation.
Mutations in the ATP1A3 gene are associated with rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC) as well as RDP/AHC intermediate presentations. Phenotypic diversity is being recognized. In order to identify ATP1A3-related phenotypes not meeting the classical criteria for RDP or AHC we lowered the threshold for mutation analysis in clinical presentations resembling AHC or RDP. A novel heterozygous ATP1A3 missense mutation c.2600G>A (p.Gly867Asp, G867D) was detected in a 15-year-old girl. Her clinical phenotype is partially consistent with an intermediate presentation between alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism and comprises additional yet unreported features. With onset at 4½ years of age recurrent paroxysmal flaccid hemiplegia alternating in laterality was triggered by watching television or playing computer games. Occlusion of both eyes reliably stopped the plegic attacks with the patient remaining awake. Our observation further widens the phenotypic spectrum associated with ATP1A3 mutations.
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Georg August University, Göttingen, Germany. Electronic address: hendrik.rosewich@med.uni-goettingen.de.
Hendrik
H
Rosewich
Department of Pediatrics, Hospital "Dritter Orden", Munich, Germany. Electronic address: M.Baethmann@dritter-orden.de.
Martina
M
Baethmann
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Georg August University, Göttingen, Germany. Electronic address: aohlenb@gwdg.de.
Andreas
A
Ohlenbusch
Department of Pediatrics and Adolescent Medicine, Division of Pediatric Neurology, University Medical Center, Georg August University, Göttingen, Germany. Electronic address: gaertnj@med.uni-goettingen.de.
Jutta
J
Gärtner
Interdisciplinary Pediatric Center for Children with Developmental Disabilities and Severe Chronic Disorders, University Medical Center, Georg August University, Göttingen, Germany. Electronic address: kbrock@med.uni-goettingen.de.
Knut
K
Brockmann
D000293:Adolescent; D020821:Dystonic Disorders / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
C488756:ATP1A3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
ATP1A3; Alternating hemiplegia of childhood; Episodic weakness; Eye closure; Paroxysmal flaccidity; Rapid-onset dystonia-parkinsonism