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

TRPHARM22 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

CTX - Cerebrotendinous Xanthomatosis

Interventions

Blood sampling for cholestanol analysisOTHER

Eligibility

Sex: ALLMax age: 40 Years

Medical Language ↔ Plain English

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.

Locations (22)

Çukurova University Medical Faculty Deparment of Metabolism

Adana, Turkey (Türkiye)

Çukurova University Medical Faculty Department of Neurology

Adana, Turkey (Türkiye)

Ankara Child and Heamatology Hospital Deparment of Metabolism

Ankara, Turkey (Türkiye)

Ankara City Hospital

Ankara, Turkey (Türkiye)

Ankara Dışkapı Yıldırım Beyazıt Research and Training Hospital Clinic of Neurology

Ankara, Turkey (Türkiye)

Gazi University Medical Faculty Department of Pediatric Metabolism

Ankara, Turkey (Türkiye)

Hacettepe University Medical Faculty Deparment of Metabolism

Ankara, Turkey (Türkiye)

Hacettepe University Medical Faculty Department of Neurology

Ankara, Turkey (Türkiye)

Osmangazi University Medical Faculty Department of Neurology

Eskişehir, Turkey (Türkiye)

Osmangazi University Medical Faculty Department of Pediatric Metabolism

Eskişehir, Turkey (Türkiye)

...and 12 more locations

Outcomes

Primary Outcomes

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)

Time frame: 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

Time frame: 3 years

Secondary Outcomes

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

Time frame: 3 Years

Cholestanol Levels

\- Cholestanol levels for patients with high cholestanol levels

Time frame: 3 Years

Patient demographics

For all screened patients: • Demographic data

Time frame: 3 Years

CTX Family History

For all screened patients: • CTX family history

Time frame: 3 Years

Presence of consangunious marriage

For all screened patients: • Presence of consanguineous marriage

Time frame: 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

Time frame: 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

Time frame: 3 Years