An Observational Study for Evaluation of for the Prevalence of Cerebrotendinous Xanthomatosis (CTX) Disease

Study Overview
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Brief Summary
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The prevalence of CTX in our country is estimated to be 1 / 50.000. The aim of this study is to screen more volunteers by conducting a larger screening from neurology and pediatric metabolism clinics in Turkey. This observational study was designed retrospectively and prospectively in two stages. In the retrospective section, the patient database and / or patient files will be screened in the neurology and pediatric metabolism clinics and the patients aged 40 and below in the neurology clinics with at least two of the following will be enrolled to the study: Ataxia and / or spasticity Bilateral cataract (except senile cataract) Intellectual limitation Non-enhancing hyperintensity on T2 sections in MR imaging of dentate nuclei Autosomal recessive transition pattern. (Ex: Relative Marriage) In the pediatric metabolism centers, cases suspected of CTX and planned to apply the Mignarri Index according to the investigator's opinion will be identified.

Official Title
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An Epidemiological Observational Study for Retrospective and Prospective Evaluation of for the Prevalence of Cerebrotendinous Xanthomatosis (CTX) Disease in Neurology and Pediatric Metabolism Clinics in Turkey

Conditions
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CTX - Cerebrotendinous Xanthomatosis

Intervention / Treatment
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* Other: Blood sampling for cholestanol analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: I-1. Giving written informed consent I-2. Patients in neurology clinics should have been identified with at least two of the following: Ataxia and / or spasticity Bilateral cataract (except senile cataract) Intellectual limitation Nonintensitive hyperintensity in T2 sections on MRI of the dentate nucleus Forming an autosomal recessive transition pattern. (Ex: Relative Marriage) I-3. In the pediatric metabolism centers, cases suspected of CTX and planned to apply the Mignarri Index according to the investigator's opinion. I-4. On the day the patient signed the Informed Consent Form, the patient did not get older than 41 years of age (subjects aged 40 and under will be included in the study) Exclusion Criteria: E-1. The patient's ataxia and / or spasticity, cataract, intellectual limitation, and non-contrasted hyperintensity of T2 sections in MR imaging of dentate nuclei with typical MRI findings are due to a known cause other than CTX or other underlying disease. E-2. The patient has participated in an interventional clinical study in the last 30 days, E-3. The patient and / or his / her legal representative does not give consent to participate in the study, E-4. In the opinion of the investigator, the patient is not able to fulfill the working requirements appropriately, E-5. Pregnancy and / or lactation E-6. If the patient was 41 years old when included in the study.

Ages Eligible for Study
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Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Blood sampling for cholestanol analysis|Blood sampling will be performed by Düzen Laboratories group for cholestanol|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with CTX possibility in Neurology Clinics | - Proportion of patients aged 40 years or younger with at least two of the following (2) in patients with a cholestanol test threshold (3.75 mg / mL) in neurology clinics: Ataxia and / or spasticity Bilateral cataract (except senile cataract) Intellectual limitation Nonintensitive hyperintensity in T2 sections on MRI of the dentate nucleus Forming an autosomal recessive transition pattern. (Ex: Relative Marriage) | 3 years | 
| Proportion of patients with CTX possibility in Pediatric Metabolism Clinics | - Proportion of cases above the cholestanol test threshold (3.75 mg / mL) in pediatric metabolism centers | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total of Mignarri Suspicion Index (SI) | Mignarri is a suspicion index, composed of weight-ed scores assigned to indicators such as family history and common systemic and neurological features. The indicators were classified as very strong (score 100), strong (50) or moderate (25). The suspicion index will be applied to study population. Early systemic signs such as catamct, diarrhea and neonatal cholestatic jaundice were considered strong indica- tors, together with neurological features such as intellectual impairment, psychiatric disturbances, ataxia, spastic paraparesis and dentate nuclei abnormalities at MRI. Tendon xanthomas were regarded as very strong indicators, as was an affected sibling. A total score 100 warranted serum cholestanol assessment. Elevated cholestanol or a total score 200, with one very strong or four strong indicators, warranted CYP27Al gene analysis. (Reference: Mignarri et al. J Inherit Metab Dis (2014) 37:421-429) -and physical examination results for patients with high cholestanol levels | 3 Years | 
| Cholestanol Levels | - Cholestanol levels for patients with high cholestanol levels | 3 Years | 
| Patient demographics | For all screened patients: • Demographic data | 3 Years | 
| CTX Family History | For all screened patients: • CTX family history | 3 Years | 
| Presence of consangunious marriage | For all screened patients: • Presence of consanguineous marriage | 3 Years | 
| Frequency of the systemic findings | For all screened patients: • Frequency of the following systemic findings: Tendon xanthomas Chronic diarrhea Prolonged neonatal jaundice Early osteoporosis | 3 Years | 
| Frequency of the neurologic findings | For all screened patients: • Frequency of the following neurological symptoms: Cerebellar ataxia Spastic paraparesis Blateral cataract (except senile cataract) Non-enhancing hyperintensity on T2 sections in MR imaging of dentate nuclei Intellectual disability Psychiatric disorders Epilepsy Parkinson's Polyneuropathy | 3 Years |