The diagnostic spectrum of ATP1A3-related disorders: 3 new patients

Background: ATP1A3-related disorders are rare but increasingly recognized syndromes with overlapping phenotypes. Clinical observations: A male child and his mother with c.2452G>A (p.Glu818Lys) mutation and an unrelated child with c.2428A>T (p.Ile810Phe) mutation in the ATP1A3 gene are reported. Results: The first child presented with fever-induced flaccid unresponsiveness and the diagnosis was made after extensive negative workup except for abnormal EMG showing low amplitude motor responses with acute denervation; his symptomatic mother went undiagnosed for thirty years until his diagnosis. An unrelated male child presented with symptoms most consistent with the rapid-onset dystonia-Parkinsonism (RDP) phenotype but with intermediate features of alternating dystonia with choreoathetoid movements two years after a c.2428A>T (p.Ile810Phe) mutation was found. Conclusion: ATP1A3-related disorders have variable manifestations and can remain undiagnosed for decades. Treatment remains mostly supportive. With the increasing use of genetic testing for broad indications, further research into effective therapies is necessary.