Prospective epidemiological observational study to determine the prevalence of cerebrotendinous xanthomatosis (CTX) disease in adult neurology clinics

This study aims to investigate the prevalence of Cerebrotendinous Xanthomatosis (CTX) disease in individuals exhibiting neurological symptoms such as ataxia, epileptic seizures, polyneuropathy, early mental deterioration, pyramidal, extrapyramidal, and cerebellar neurological signs and symptoms with unexplained etiology, and who are suspected to have a progressive neurodegenerative disease. The research is a single-center, hospital-based, descriptive cross-sectional study conducted on patients who presented to the neurology clinic with chronic neurological symptoms thought to be associated with neurodegeneration but with an undetermined etiology. Demographic features, complaints, physical and neurological examination findings, and imaging results of the patients were recorded. Genetic examination using next-generation sequencing was performed on peripheral blood to investigate the presence of homozygosity or heterozygosity in the CYP27A1 gene region. The study included 71 patients with an average age of 27.7 years, of whom 44 (62.0%) were male. The majority of patients (81.8%) were born in Gaziantep, and the three most common complaints were seizures (57.7%), gait abnormalities (%42,2) and mental retardation (%28.2). Systemic findings included juvenile cataract in 5 patients (7.0%), tendon xanthomas in 3 patients (4.2%), and childhood-onset chronic diarrhea in 2 patients (2.8%). The most common neurological manifestation was epilepsy (60.6%), followed by intellectual disability (43.7%), pyramidal involvement (40.8%), developmental delay (33.8%), cerebellar involvement (33.8%), ataxia (31.0%), parkinsonism (26.8%), and polyneuropathy (7.0%). The most common magnetic resonance imaging finding was cerebral focal lesions (29.6%), followed by white matter involvement (19.7%), non-specific lesions (9.9%), cerebral atrophy (9.9%), cerebellar atrophy (7.0%), dentate nucleus signal abnormality (5.6%), basal ganglion involvement (5.6%), cerebellar focal lesions (4.2%), and brainstem focal lesions (1.4%). In 24 patients (33.8%), electroencephalogram revealed irregularities characterized by sharp slow waves, while 14 patients (19.7%) showed epileptiform potentials characterized by sharp slow waves, and 7 patients (9.9%) exhibited slow activity. Three patients (4.2%) included in the study were found to be CTX positive. Among CTX-positive patients, 2 had a history of seizures, with an average age of onset of 15.5 years. All CTX-positive patients exhibited intellectual disability and walking difficulties, with average ages of onset being 3.67 years and 29.33 years, respectively. While no patient had tremors, 2 had vision problems, and 1 had other symptoms. When the clinical-pathological histories of CTX-positive patients were evaluated together, it was observed that neurological symptoms developed in childhood were attributed to infectious health problems such as meningitis, which had a genetic basis and could be curatively treated with early diagnosis, and as a result, remained untreated for years due to the inability to perform advanced investigations and establish a diagnosis. Early diagnosis through genetic evaluation of CTX disease can prevent the development of morbidity after treatment.