HUMBLE COFFEE | Therapy for Rare Involuntary Movement Disorder

PIB News Update: Genetic diseases can be caused due to mutations or alterations in genes in the cells of our body.  Most of the genetic diseases are not treatable and hence genetic counselling and prevention of these diseases is the only available modality for these families.  Although novel therapies are being developed for some genetic diseases, these therapies are very expensive and out of reach of common public.  Accurate diagnosis of genetic disease is very important for proper management and prognosis.  The advent of newer diagnostic modalities based on high throughput next generation sequencing has made it possible for diagnosis of a significant number of patients with genetic diseases and these facilities are now readily available at multiple centres throughout the country.  We wish to report regarding diagnosis of one such patient and subsequent therapy using the “humble coffee” which changed his life.

Mr Ramesh (name changed), a 33 year old man presented to the outpatient department of Neurology clinic/Genetics clinic at Mazumdar Shaw Medical Center, Narayana Hrudayalaya Hospitals, Bengaluru where he was seen by Neurologist Dr. Kuldeep  Shetty and Medical  Geneticist Dr. S.J. Patil.  The man complained of involuntary movements of limbs and face since 5 years age. The movements used to happen in bouts of 10 to 15 times per day, lasting for few minutes and were affecting his activities of daily living.  Such features are termed as paroxysmal dyskinesia and alterations in more than 12 genes are known to result in this phenotype.  Since many genes needed to be tested, genetic testing using high through put sequencing technology called exome sequencing analysis done on research basis by a team led by Dr. Aswin Dalal, Head, Diagnostics Division at Centre for DNA Finger printing and Diagnostic, Hyderabad to identify genetic basis in this patient.  The sequencing revealed a mosiaic mutation in ADCYS (adenylate cyclise) gene.  Identification of low level mosaic mutations is not possible by traditional methods of sequencing and hence the use of the new technology of exome sequencing helped us to detect this mutation.  We conveyed this information to the patient regarding the cause of his involuntary movements. This condition is known to be not very well responsive to the currently available medications (like benzodiazepines, betablockers, tetrabenazine, anticholinergics etc).  Some of these drugs were tried with no benefits in our patient.

In June 2019, a group of scientists from France reported an unusual phenomenon wherein, they found that in a family with father and daughter affected with similar involuntary movements and having mutation in ADCYS gene, there was reduction of movements on consumption of coffee.  In order to check this they recruited an 11 year old boy with involuntary movements who was found to have mutations in ADCY5 gene and gave him high dose of coffee in form of espresso coffee as three doses per day.  They were surprised to see that his involuntary movements decreased from 30 bouts per day to one or two brief movements within few days of “coffee” treatment.  Interestingly the movements.  Reappeared when the patient was give decaf coffee by the family and disappeared again when caffeine containing coffee was given.  In view of this interesting report.  We called our patient and started him on coffee regimen which resulted in 90% reduction in his involuntary movements within few days of treatment.  The treatment with a simple food product has brought smiles to this man’s life and hopefully will help him in improvement of his activities of daily living as well as his profession.  Long term follow up will be done to understand its long term use and benefits.  The mechanism of action of caffeine is thought to be through its property of being an antagonist of adenosine.  Thus caffeine prevents formation of excess cyclic AMP, which is responsible for the involuntary movements, by inhibiting its synthesis through blocking of adenosine receptors in brain.

The aim of this report is to make public aware regarding the various new modalities of diagnosis of genetic diseases and their availability at various places in our country.  These technologies enable us to find genetic defects which would not have been possible with traditional testing methods.  Further we would also be happy if we are able to find more patients with mutation in this gene and having disabling involuntary movements, who could be helped using a simple and cheap food product as a treatment, so that they can lead a happy and productive life.  Hopefully more number of treatments is expected to be discovered in the near future through insights of genetic basis of inherited disorders.