Fabry Disease, Cardiac Variant
Conditions
Brief summary
Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (GLA) gene mutations leading to reduced or undetectable α galactosidase A (α-Gal A) enzyme activity, resulting in progressive accumulation of globotriaosylceramide (GL3) and its deacylated form globotriaosylsphingosine (Lyso-GL-3) in multiple organs, causing neural, renal, cardiac, dermatological, gastrointestinal and ophthalmic manifestations, even leading to life-threatening complications. Cardiovascular and cerebrovascular complications (i.e. heart failure, stroke, etc.) or end-stage renal disease even premature death can be seen in severe cases. The life expectancy of male patients is reduced by 15\ 20 years, while that of female patients is reduced by 6\ 10 years. The exact prevalence of FD is currently unknown. Based on an estimated prevalence of 1:60,000, there are approximately 23,000 affected FD patients in China. The clinical manifestations of FD are diverse and non-specific, which may lead to misdiagnosis in patients with non-typical clinical manifestations in the absence of a family history of FD. Cardiac involvement can be recognized in up to 68% patients with FD, significantly higher than in other organs, and the positive screening rate for FD in adults with unexplained left ventricular hypertrophy (LVH)/hypertrophic cardiomyopathy was 0.9%. Cardiovascular disease is the leading cause of death in patients with FD cardiomyopathy (40.2%). The 2020 Expert Consensus Document on the Management of Cardiovascular Manifestations of Fabry Disease recommends early screening in patients with suspected LVH for early diagnosis. Therefore, strengthened screening strategy in high-risk patients with LVH will improve the diagnosis and treatment of FD in China.
Interventions
None listed
Sponsors
China National Center for Cardiovascular Diseases
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patients to be enrolled in this study should fulfill all 3 criteria (a, b, and c) at screening: 1. Patients with a maximum myocardial wall thickness (left ventricular posterior wall or septum) of ≥13 mm at the end diastole on echocardiography; 2. At least two or more warning signs associated with FD (warning signs include cardiac warning signs, extracardiac warning signs, or family history) 3. Aged 18 years old or older; cardiac warning signs of FD: Concentric LVH or papillary hypertrophy or right ventricular hypertrophy on echocardiography ECG abnormalities (eg, shortened PR interval, wide QRS complex, right bundle branch block, ST-segment depression, etc.) Extra-cardiac warning signs of FD Angiokeratomas Acroparesthesia Hypohidrosis Premature stroke (\<50 years of age) Corneal verticillate Renal impairment accompanied by proteinuria Hearing loss Family history Family history of X-linked inherited disorder (renal disease or cardiac disease)
Exclusion criteria
1. LVH patients with a clear etiology; 2. Combining any other clinical condition with a life expectancy less than 1 year; 3. Refuse to give informed consent or refuse to be followed-up.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cardiovascular deaths | 12 months | Including sudden cardiac death or equivalent events, heart failure-related death, stroke-related death and death from other cardiovascular causes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Heart failure | 12 months | NYHA progression to level III/IV |
| Stroke | 12 months | Including ischemic stroke and hemorrhagic stroke |
| Myocardial infarction | 12 months | Including ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction |
| All-cause deaths | 12 months | Death from all causes |
Countries
China
Contacts
Primary ContactLei Song
Outcome results
None listed