[Abstract] Background 

Left ventricular
hypertrophy is one of the major manifestations of Fabry disease. Numerous studies have reported the high prevalence of Fabry disease among patient with cardiac symptoms. However, the prevalence of Fabry disease has not been reported in Macau previously.

Objective

To investigate the prevalence of Fabry disease (FD) with left ventricular hypertrophy (LVH) for adult in Macau.

Methods

To be eligible for screening, patients should be at least 18 years old with diagnosis of LVH which is defined as the thickness of the maximal left ventricular wall is or more than 13mm by echocardiogram. The exclusion criteria include known hypertrophic cardiomyopathy due to sarcomere mutations, left ventricular non-compaction,
infiltrating cardiomyopathies, athletic heart, morbid obesity, known non-FD metabolic or syndromal conditions associated with LVH. The initial diagnostic screening method involves GLA enzyme test and/or biomarker test with lyso-Gb3, dry blood spot(DBS) test for male (α-GAL≤1.8uM/hr) and blood test for female (α-GAL≤1.8uM/hr and/or Lyso-GL3 ≥0.8ng/mL), which is carried out by National Taiwan University Hospital. Patients who have low enzyme activity level will proceed to genetic test for diagnosis confirmation. The genetic test is under the GenePhile Bioscience Lab in Taiwan. For patients with positive genetic tests, their family were suggested to receive further screening test.

Results

A total of 43 patients with LVH were enrolled in the study from Kiang Wu Hospital in Macau from March
2019 till Jan 2020. The mean age of patients was 64.93±17.22 years old. The maximal IVS thickness was 17.17±5.52mm, and the maximal LVPW thickness was 12.14±2.43mm. One male patient (aged 48) was found to have low enzyme activity (α-Gal A: 0.71uM/hr) and has proceeded to genetic analysis. FD diagnosis with cardiac variant [c.639+919G>A] was confirmed. This patient is the first diagnosed patient of Fabry disease in Macau. 9 persons of his families were received the initial diagnostic screening test, while 6 of them including his mother, two elder sisters, his daughter, one nephew and one niece have positive results in genetic test. One female patient (aged 47) was found to have low enzyme activity (α-GalA: 1.05uM/hr; Lyso-GL3: 0.16ng/mL) but has negative result in genetic test. Another female patient (aged 60) was found to have elevated biomarker level (Lyso-GL3: 6.66ng/mL) and found with gene mutation [c.-10C>T; c.640-16A>G; c.1000-22C>T] in genetic test, and later confirmed as FD with exon 2 deletion of GLA gene through MLPA test. Her families would receive the initial
diagnostic screening test and genetic test. The confirmed FD patients will be referred to assess their eligibility for enzyme replacement therapy. All the FD patients were followed up regularly.

Conclusion

Two patients (4.65%) were identified as Fabry disease among 43 patients with LVH, including one among these 2 FD patients (2.33%) was identified as Cardiac variant. Family screening performed further identified six more FD patients. The screening of FD in patients with LVH could help doctors to detect and follow up the FD patients.

Article was submitted on January of 2020.

Screening test of Fabry Disease with left ventricular hypertrophy (LVH) for adult in Macau

ECHO ASIA is organized by Asian-Pacific Association of Echocardiography (AAE). The meeting combines the basic echocardiography training curriculum and the state-of-the-art lectures/scientific sessions provided by international as well as Asian-Pacific experts. The meeting is a unique forum where scientists from many countries in the Asian-Pacific region who are involved in the field of Doppler echocardiography gather together to exchange knowledge and skills. Various internationally distinguished faculties consent to present their findings and reveal their clinical experiences in ECHO ASIA.