Challenges in diagnosis of fragile X-associated tremor/ataxia syndrome

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease recently described in the literature with a low percentage of detectability in patients due to insufficient awareness of doctors. The clinical picture is characterized by high phenotypic variability and coincidence of symptoms with other, more well-known motor disorders, in connection with which patients are observed for a long time with erroneous diagnoses. The issue of the differential diagnosis fragile X-associated tremor/ataxia syndrome with essential tremor, Parkinson’s disease, multiple system atrophy, spinocerebellar ataxia and progressive supranuclear paralysis is highlighted separately. In order to demonstrate the complexity of the diagnosis of this disease, a description of a case of genetically confirmed case of genetically confirmed fragile X-associated tremor/ataxia syndrome is presented. The described clinical case is represented by a combination of asymmetric disabling postural kinetic tremor of the hands, minor resting tremor, moderate cerebellar ataxia, asymmetric moderate dopa-responsive parkinsonism syndrome, mild cognitive impairment and psychotic symptoms. Not only the clinical picture of the disease is described in detail, but also the hereditary history of the patient: the results of a genetic study of a daughter premutation carriers of the FMR1 gene and a grandson suffering from Martin–Bell syndrome. A special feature of the clinical case is the long-term erroneous observation of a patient diagnosed with Parkinson’s disease, as well as high-dose therapy with levodopa/carbidopa 250 mg + 25 mg (up to 6 tablets per day). When studying the available domestic literature, the previously described cases of fragile X-associated tremor/ataxia syndrome were not found.