An almost 8 years girl with a KCNMA1 mutation (chr10:g.78651467T>C(GRCh37) c.2996A>Gp.Asn999Ser) would have countless daily paroxysms with loss of tone and gradual collapse. Efforts to treat these with a variety of medications were unsuccessful. The medications included levetiracetam, oxcarbazepine, clonazepam, imipramine, acetazolamide and ethosuximide. The patient’s mother through a KCNMA1 parent network heard of a boy with evidently an identical mutation who at 9 years of age was prescribed lisdexamfetamine dimesylate (Vyvanse) for attention deficit symptoms. Concurrent with lisdexamfetamine administration, there was a remarkable abolition of his paroxysmal episodes. This had continued for 10 years. When lisdexamfetamine effect wears off, the episodes promptly recurred.
Upon hearing of this, I asked the mother whether she would be interested in trial of lisdexamfetamine therapy for her daughter. At first she demurred, but, after discussing it with her daughter, she gave a try with lisdexamfetamine at a 10 mg dosage. That day her daughter had 6 episodes instead of “hundreds”. The next day it was 4 episodes. On the third day, no episodes occurred, which had never previously happened. Subsequently, the lisdexamfetamine dose was increased to 20 mg. The patient is episode free during the day. In the evening, when lisdexamfetamine effect wore off, episodes would again occur.
The mother is aware of one other child treated successfully with lisdexamfetamine and another child, evidently with evidence of significant cerebral disease, who did not benefit . The mutation here is a gain of function mutation. The mother suggests that only patients with KCNMA1 gain of function mutation seem to benefit from lisdexamfetamine.