Fabry Disease in Cerebrovascular Disease

Study Overview
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Brief Summary
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Fabry disease is an X-linked disorder of glycosphingolipid catabolism caused by a deficiency of the enzyme α-galactosidase A (α-Gal A), which leads to a progressive accumulation of globotriaosylceramide (Gb-3) in plasma and tissue lysosomes throughout the body. Lysosomal accumulation can result in lysosomal and cellular dysfunction, which leads to renal, cardiac, and central nervous system (CNS) complications. It is estimated that 1 in 40,000 males has Fabry disease, whereas the estimated prevalence in the general population is 1 in 117,000 people. Newborn screenings for both classical and atypical Fabry disease in Taiwan also revealed a markedly high incidence of 1 in 2,300 and 1 in 3,000 newborns. Cerebrovascular variant Fabry disease may affect up to 4.9% of male patients and 2.4% of female patients with idiopathic stroke. The diagnosis of Fabry disease can be challenging due to the diverse signs and symptoms, different ages of onset, and variable timing and severity of progression. The importance of Fabry disease lies in the irreversible renal, cardiac, cerebrovascular, and neurological damage. An early diagnosis of Fabry disease is important for initiating symptom management and reducing life-threatening complications, as well as for early identification of other affected family members. Therefore, the present study would like to conduct further screening of high-risk group of early cerebrovascular involvement that is essential for the successful management of Fabry disease.

Detailed Description
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This is a cross-sectional, population-based study to identify Fabry disease in patients with early cerebrovascular involvement. Eligible patients are age above 18 years old (<=55 years old) with early cerebrovascular involvement and have provided inform consent. Patients who have been diagnosed Fabry disease are not eligible. The present study will use samples of early cerebrovascular involvement patients which have been enrolled in two previous IRB approved projects [103-3254C (origin 98-3889A3), 100-4008C (origin 97-0470B)], participants of both studies have consented that participants' samples could be further investigated if needed. Since, the investigators cannot ensure whether the condition of enzyme activity of frozen plasma sample were decayed after long-term storage and the investigators don't have available normal range of enzyme activity of historical plasma sample, the investigators will perform specific genotyping of Fabry disease for these patients according to the specific mutation variants which have been identified in Taiwan population previously. Patients will be recalled to assess Fabry related symptoms if genetic testing has mutation finding and family screening will be performed if applicable. Further inform consent will be obtained as well.

Official Title
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Improving the Diagnostic Rate of Fabry Disease in Patients With Cerebrovascular Involvement in Taiwan- a Cohort Screening Program

Conditions
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Fabry Disease

Intervention / Treatment
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* Genetic: 26 common Fabry mutation types in Taiwan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age >= 18 y/o Both females and males who have ischemic or hemorrhagic stroke before the age of 55 y/o Patient or his/her legal representatives are willing to sign the informed consent Exclusion Criteria: Ischemic or hemorrhagic stroke patients who are already diagnosed to have Fabry disease

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Young stroke<br>Historical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing for the 26 common Fabry mutation types in Taiwan. | Genetic: 26 common Fabry mutation types in Taiwan<br>* Historical DNA samples from projects 103-3254C (98-3889A3) and 100-4008C (97-0470B) will perform specific genetic testing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Conclusive diagnosis of Fabry disease |  | 12 months |