Intractable Rare Dis Res. 2019;8(1):67-71. (DOI: 10.5582/irdr.2018.01133)
A novel mutation in CACNA1A gene in a Saudi female with episodic ataxia type 2 with no response to acetazolamide or 4-aminopyridine.
Algahtani H, Shirah B, Algahtani R, Al-Qahtani MH, Abdulkareem AA, Naseer MI
Episodic ataxia is a genetically heterogeneous neurological condition characterized by spells of incoordination and imbalance, often associated with progressive ataxia. Episodic ataxia type 2, caused by calcium voltage-gated channel subunit alpha1 A (CACNA1A MIM: 601011) mutation, is the most common form of episodic ataxia. It is characterized by recurrent attacks of imbalance associated with interictal nystagmus lasting hours to days and triggered by emotional stress or exercise. In this article, we report a novel heterozygous intronic variant c.5743+14A>G in the CACNA1A gene in a Saudi family. To the best of our knowledge, this variant has not been described in the literature or reported in public mutation databases. This report indicated that acetazolamide is not beneficial, and it may be even harmful to patients with episodic ataxia type 2 if used in later stages. In addition, treatment with 4-aminopyridine did not show any efficacy to improve walking or balance in our patient, which indicates the importance of early initiation of therapy before the later stages of the disease. Further research is needed to explore potential treatments for this challenging disease.