Fabry disease (FD) is a genetic condition where mutations in the GLA gene cause low activity of an important enzyme (alpha-Galactosidase A). This leads to harmful substances building up in the body. A key marker is lyso-Gb3, which can damage organs. FD commonly affects the heart, causing left ventricular hypertrophy (LVH), fibrosis, and worsening heart function over time. In East Asian populations, the exact natural progression of FD is not well understood, even though a specific mutation called IVS4+919G\>A is relatively common due to a "founder effect" seen in places like Taiwan and also in Hong Kong. People with this mutation often develop heart problems later in life, with LVH typically increasing after about age 40. Researchers use advanced heart scans to detect early disease. Cardiac MRI (CMR) native T1 mapping (without contrast) can distinguish normal heart tissue from FD-related changes. CMR measures can reflect different stages of heart damage-starting with accumulation, then inflammation and muscle thickening, and finally fibrosis and impaired function. Some women may not have clear blood test abnormalities yet can still develop ongoing heart damage. Because some MRI findings (like late gadolinium enhancement, LGE) may represent inflammation as well as fibrosis, and because heart damage can progress even before symptoms appear, non-invasive monitoring is important. Imaging methods like strain echocardiography and repeated T1 mapping can track progression, including in patients without obvious early heart thickening. Finally, since most previous studies have included fewer East Asian patients, the study aims to better define the natural history of FD in Chinese patients with the IVS4+919G\>A mutation by following them over time with regular health checks, blood and enzyme testing, kidney and heart function tests, and family/genetic mapping. The goal is to improve guidelines for screening, monitoring, and deciding when to start treatment (ERT).
Study Type
OBSERVATIONAL
Enrollment
31
Division of Cardiology, Department of Medicine and Therapeutics Faculty of Medicine, The Chinese University of Hong Kong
Shatin, New Territories, Hong Kong
Disease progression - Left Ventricular mass index
The Left Ventricular mass index quantifies the mass of the left ventricle, the heart's main pumping chamber, relative to an individual's body size. This will be measured using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - Papillary muscle mass index
Papillary muscle mass refers to the total amount of tissue (mass) in the papillary muscles located within the left ventricle. These muscles help support the mitral valve and play an important role in how the left ventricle pumps blood during systole. This measurement will be obtained using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - LVEF
LVEF, or Left Ventricular Ejection Fraction, indicates how well the left ventricle pumps blood. This will be measured using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - LVEDV
LVEDV, or Left Ventricular End-Diastolic Volume, is the amount of blood in the left ventricle at the end of diastole, right before the heart contracts. This will be measured using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - LVESV
LVESV stands for Left Ventricular End-Systolic Volume and refers to the volume of blood remaining in the left ventricle after pumping. This will be measured using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - Native T1 mapping
Native T1 is a heart MRI measurement that looks at the properties of the heart muscle tissue without using contrast dye. It helps detect early or subtle tissue changes, such as inflammation or remodeling, even when scarring isn't yet obvious. This will be obtained during cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - LGE volume
LGE volume refers to the measurement of Late Gadolinium Enhancement, a cardiac MRI method used to estimate how much heart muscle has developed fibrosis (scarring). This measurement will be obtained using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - Number of LGE-positive segments
LGE positive refers to Late Gadolinium Enhancement and is used to visualise and assess myocardial damage or scarring. This measurement will be obtained using cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - ECV
Extracellular Volume (ECV) it's a measurement from cardiac MRI that estimates how much of the heart muscle's space is in the outside (between-cell) area, which can increase when there's things like fibrosis (scarring) or other tissue remodeling. This measurement will be obtained with T1 mapping during cardiac MRI.
Time frame: Baseline, 12 months follow-up and 24 months follow-up
Disease progression - LV end-diastolic septal thickness
Left Ventricle end-diastolic septal thickness is the thickness of the septum, the wall between the left and right sides of the heart, measured at the end of diastole, just before the heart contracts. This measurement indicates how thick that part of the heart wall is when the ventricle is fully filled. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18-and 24-month follow-up
Disease progression - LV end-diastolic posterior wall thickness
Left Ventricle end-diastolic posterior wall thickness is a measure of how thick the back wall of the left ventricle is at the end of heart filling. This measurement will be obtained during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - LV maximal wall thickness
Left ventricular maximal wall thickness measures how thick the heart muscle is at its thickest point on the left ventricle wall. This measurement will be taken during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Left Ventricular Ejection Fraction (LVEF)
Left Ventricular Ejection Fraction (LVEF) is a measure of how well the left side of the heart pumps. It shows what percentage of blood in the left ventricle is pushed out with each heartbeat. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Left Ventricular End-Diastolic Volume (LVEDV)
Left Ventricular End-Diastolic Volume (LVEDV) is the amount of blood left in the left ventricle at the end of diastole. This measurement will be taken during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Left ventricular end-systolic volume (LVESV)
Left ventricular end-systolic volume (LVESV) is the amount of blood left in the left ventricle right after it contracts. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Left Atrium Volume (LA volume)
Left Atrium Volume (LA volume) means the size of the left atrium and is a measurement of how much space or blood the left atrium holds. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Right Ventricle Volume (RV Volume)
Right ventricular volume refers to the amount of blood in the right ventricle, usually measured at end-diastole (when the heart is filling) and end-systole (when it has squeezed). This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Right Ventricular Systolic Pressure (RVSP)
Right Ventricular Systolic Pressure (RVSP) measures the pressure generated by the right ventricle as it pumps blood into the pulmonary artery. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - LV global longitudinal strain (GLS)
LV global longitudinal strain (GLS) is a measurement of how well the left ventricle is squeezing by looking at how much the heart muscle shortens in length during each heartbeat. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Left Atrial strains (LA strains)
Left Atrial strains (LA strains) is a measurement of how well the left atrium is working, by tracking how much it stretches and squeezes during the heartbeat. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Right Ventricle free wall
The Right Ventricle free wall refers to the outer/free edge of the right ventricle and is used to assess how well the right ventricle is contracting and working.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Septal longitudinal strain
Septal longitudinal strain is a measure of how much the septum (the wall in the middle of the heart that separates the left and right sides) lengthens and shortens from the base to the tip of the heart during each heartbeat. This will be measured during echocardiography.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Plasma lyso-Gb3
Plasma lyso-Gb3 is a blood test that measures a substance called lyso-globotriaosylsphingosine (lyso-Gb3). In Fabry disease, the body can't properly break down certain fats, because of that, lyso-Gb3 can build up. This is used as a biomarker to diagnose Fabry disease and to monitor disease progression. This will be obtained during a blood test.
Time frame: Baseline, 12- and 24 months
Disease progression - NT-proBNP
NT-proBNP is a blood biomarker released by the heart that indicates cardiac stress and helps diagnose and monitor heart failure. This will be obtained during a blood test.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Troponins
Cardiac troponins are proteins that leak into the bloodstream when the heart muscle is injured. They are used to help diagnose heart attacks and other types of heart damage. This will be measured using a blood test.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Urinary protein
Measuring urinary protein is an important way to check how well the kidneys are working. This will be measured by collecting a urine sample.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression - Albumin
Albumin is a protein made by the liver and is essential for maintaining fluid balance and transporting substances throughout the body. This will be measured by collecting a blood test.
Time frame: Baseline, 6-, 12-, 18- and 24 months follow-up
Disease progression and disease severity - MSSI (Mainz Severity Score Index)
MSSI (Mainz Severity Score Index) will be used to measure how severe the disease is overall and how the participants' health changes overtime or in response to treatment. A higher MSSI score means the disease is more severe.
Time frame: Baseline, 6-, 12-. 18- and 24-month follow-up
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Disease progression - NYHA class
A NYHA class (New York Heart Association) questionnaire will be used to assess the heart failure severity and the impact on the patients' daily activities and overall functional capacity. The scores are divided into Class I (1) to Class IV (4) with Class I meaning no limitations and Class IV meaning severe limitations.
Time frame: Baseline, 6-, 12-. 18- and 24-month follow-up
Mortality
Mortality will be recorded during the study period.
Time frame: This will be assessed from baseline, 6-, 12-, 18- and 24-month follow-up
Disease progression - New onset of Heart Failure
Any new onset of heart failure will be recorded throughout the study. This will be assessed by capturing evidence of cardiac deterioration and heart failure symptoms using standard tools such as the NYHA questionnaire and echocardiography.
Time frame: This will be assessed starting from baseline, then at 6-, 12-, 18- and 24-month follow-up.
Disease progression - Arrhythmia
Detected rhythm abnormalities/events during follow-up will be documented and analysed as part of disease progression. This will be assessed using standard 12-lead ECG and 24-hour Holter ECG.
Time frame: The standard 12-lead ECG will be conducted at baseline, 6-, 12-. 18- and 24-month follow-up. The 24-hour Holter ECG will be conducted at 12- and 24-month follow-up
Disease progression - Cardiac hospitalisation
Any hospitalisation due to a cardiac cause will be assessed and recorded throughout the study, and this will be evaluated at the scheduled clinical visits.
Time frame: Starting from baseline and then at 6-, 12-, 18- and 24-month follow-up