Dyskinesias
Conditions
Keywords
ADCY5 mutation
Brief summary
Heterozygous mutations in the ADCY5 gene cause involuntary early-onset hyperkinetic movements. In addition, patients may have associated psychiatric disorders.There is currently no treatment. As the pathophysiology is linked to ADCY5 hyperactivity, the investigative team has treated patients with caffeine, an antagonist. The investigator wishes to interview patients on the effect of caffeine on their motor symptoms and their overall clinical condition, and on the possible existence of psychiatric comorbidities using phone questionnaires.
Detailed description
Heterozygous mutations in the ADCY5 gene cause involuntary early-onset hyperkinetic movements. The phenotype combines chorea, dystonia and / or myoclonus with frequent facial involvement, axial hypotonia, fluctuations and / or episodes of paroxysmal dyskinesia which can be nocturnal and / or painful. Many treatments have been tried, with no obvious efficacy. Two patients from the same family (a father and daughter) told investigators that caffeine had a dramatic effect on their paroxysmal episodes. They said that taking coffee would prevent episodes and reduce their duration (efficacy estimated at 80%), an effect specific to caffeine since it was reproduced by the ingestion of caffeine citrate capsules. Very interestingly, there is a rationale underlying this phenomenon. Indeed, caffeine is an antagonist of the adenosine A2A receptors (A2AR), receptors which activate ADCY5 and which are localized preferentially in striatal neurons expressing dopamine D2 receptors. As caffeine is an A2AR antagonist, it likely inhibits ADCY5, and therefore induces clinical improvement in patients with hyperactivity of this protein. In addition, the investigative team noted anxiety in some of its patients, and the question of the presence of psychiatric disorders in ADCY5 patients was recently raised in the literature. The investigative team wishes to collect standardized preliminary data by questioning patients on the effect of caffeine on their motor symptoms and their overall clinical state, and on the possible existence of psychiatric comorbidities using structured questionnaires which will be carried out by phone.
Interventions
None listed
Sponsors
Institut National de la Santé Et de la Recherche Médicale, France
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
8 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Proven genetic diagnosis of ADCY5-related dyskinesia * Caffeine intake * Non opposition by the patient or the legal representatives if the patient is a minor. No
Exclusion criteria
.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of responders to caffeine | one hour | the response being defined as an improvement of overall involuntary movements of 40% or more. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global change of involuntary movements ranging from 0 (no change) to 10 (disappearance of involuntary movements) | one hour | evaluated by patients |
| Global clinical change ranging from 0 (no change) to 10 (normalization of the global clinical state) | one hour | evaluated by patients |
| Change of the duration of paroxysmal episodes of movement disorders with caffeine | one hour | evaluated by patients |
| Frequency change of paroxysmal episodes of movement disorders with caffeine | one hour | evaluated by patients |
| Presence or absence of psychiatric symptoms | one hour | according to the MINI (Mini International Neuropsychiatric Interview) |
Countries
France
Outcome results
None listed