Cardiovascular manifestations of Fabry disease: relationships between left ventricular hypertrophy, disease severity, and alpha-galactosidase A activity.
OBJECTIVE
Fabry disease is a rare X-linked deficiency of alpha-galactosidase A (alphagal), which causes glycosphingolipid accumulation. This study analysed the cardiovascular manifestations of a cohort of Fabry patients, and sought to define relationships between disease severity, alphagal activity, and cardiac abnormalities.


RESULTS
We prospectively analysed Fabry patients (139 subjects: 92 males and 47 females) undergoing screening for potential enzyme replacement therapy. Baseline echocardiograms, electrocardiograms, and exams were obtained as part of two multinational clinical trials. Cardiovascular symptoms were present in 60.4%. By echocardiography, the mean left ventricular mass index (LVMI) was increased at 165.5 +/- 66.9 g/m(2), and 84.8% of patients displayed concentric left ventricular hypertrophy (LVH). Electrocardiographic LVH was present in >50% of adult subjects. In females, log-corrected plasma alphagal activity was inversely associated with LVMI (r = -0.45, P < 0.040). Males with extremely low alphagal activity and renal disease displayed the most LVH and cardiac symptoms, but LVH was prevalent even in females <20 years old.


CONCLUSIONS
Concentric LVH was the predominant cardiac pathology seen in patients with Fabry disease, and was prevalent in both genders by the third decade of life. Left ventricular mass index was inversely correlated with alphagal activity, but was prevalent even in younger females.
Wu
Justina C
JC
Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA.
Ho
Carolyn Y
CY
Skali
Hicham
H
Abichandani
Rekha
R
Wilcox
William R
WR
Banikazemi
Maryam
M
Packman
Seymour
S
Sims
Katherine
K
Solomon
Scott D
SD
D000293:Adolescent; D000328:Adult; D000368:Aged; D004452:Echocardiography; D000795:Fabry Disease / Q000150:complications / Q000201:enzymology*; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000201:enzymology* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D055815:Young Adult; D000519:alpha-Galactosidase / Q000378:metabolism*
D000519:alpha-Galactosidase