Background: Episodic ataxia type 2 (EA2) is an autosomal dominant genetic disorder, caused by pathogenic variants in the CACNA1A gene. EA2 is characterized by paroxysmal attacks of ataxia, vertigo, imbalance, and variably nausea, migraine, and epilepsy. Symptoms typically begin before the age of 20.
Methods: Here, we present two unrelated patients with EA2 referred to a neuromuscular disease center for evaluation for suspected periodic paralysis (PP).
Results: Both patients reported episodes of imbalance affecting the ability to walk and slurred speech.
Patient 1 was adopted, with little information available regarding his biological family. Patient 2 endorsed a dominant family history of similar episodes in his sister, niece, mother, and maternal grandmother.
Electromyography and nerve conduction studies were normal in patient 1; no long exercise test was performed. Patient 2 underwent a long-exercise test (baseline amplitude 10.76mV), which showed an initial intra-exercise increment (14.6mV), followed by post-exercise decrement (6.24mV,), consistent with a disorder of muscle membrane excitability.
Both patients harbor a variant of uncertain significance (c.5216C>T, p.F1739S) in the CACNA1A gene. Segregation studies in the affected family members are pending.
Patient 2 reported worsening symptoms with acetazolamide. His attacks nearly resolved with Diclofenamide (from daily attacks to 2 over six months). Patient 1 was started on acetazolamide for prevention of ataxia episodes, and reported significant reduction in frequency and severity of episodes.
Conclusion: The identification of the F1739S variant in two patients with EA2 strongly suggests pathogenicity of this genetic finding. These cases highlight the need to consider EA2 in the diagnostic and genetic evaluation of patients with periodic loss of ambulation and abnormal long-exercise testing. Additional studies may help understand the overlap between these disorders. Case 2 suggests Dichlorphenamide, another carboanhydrase inhibitor, may be an effective therapy in EA2 patients when there is no noted benefit with acetazolamide.