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Caffeine significantly reduces frequency of Paroxysmal Dyskinesia in a child with an ADCY5 Mutation

Caffeine Significantly Reduces Frequency of Paroxysmal Dyskinesia in a Child with an ADCY5 Mutation

Background ADCY5 mutation is one of the causes of early-onset paroxysmal non-kinesogenic dyskinesia (PNKD). Case Report This 7-year-old girl with unremarkable perinatal and family histories, presented with developmental delay and unusual body movements since 18 months of age. She had been experiencing episodic brief, jerky movements of upper limbs and fidgety movements of hands suggestive of myoclonus and chorea. She subsequently developed perioral dyskinesias with slurring of speech and drooling. The episodes were more upon awakening in the mornings and worsened with stress and infections. Interictal examination was remarkable for axial and peripheral hypotonia, normal reflexes, wide-based gait, "jack in the box" tongue sign and milkmaid sign. Extensive neurometabolic work-up was negative. Clinical exome analysis revealed de novo heterozygous pathogenic variant c.1253G>A [p.Arg418Gln] in exon 2 of ADCY5 gene. A trial of oxcarbazepine wasn’t satisfactory. However, her movements significantly improved when she was given caffeine in a dose of 40mg twice a day, with no major side effects. Discussion ADCY5 gene encodes adenylyl cyclase(AC5) that converts adenosine triphosphate to cyclic adenosine-3′,5′-monophosphate(cAMP) in the striatum. Caffeine causes AC5 inhibition and thus reduction of cAMP production, with positive results reported in few patients. Other pharmacologic agents haven’t been successful while Deep brain stimulation (DBS) seems to provide modest improvement. Conclusion Caffeine appears to be an effective novel therapeutic agent in ADCY5-related dyskinesias. More research is needed to determine appropriate doses and formulations as well as long term effects.
Keywords: paroxysmal, dyskinesia, movement disorder ,caffeine