Prevalence of Fabry Disease in Korean Men with Left Ventricular Hypertrophy

Woo-Shik Kim, Hyun Soo Kim, Jinho Shin, Jong Chun Park, Han-Wook Yoo, Toshihiro Takenaka, Chuwa Tei, Woo-Shik Kim, Hyun Soo Kim, Jinho Shin, Jong Chun Park, Han-Wook Yoo, Toshihiro Takenaka, Chuwa Tei

Abstract

Background: Fabry disease is an X-linked recessive disorder caused by deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A). Previous studies identified many cases of Fabry disease among men with left ventricular hypertrophy (LVH). The purpose of this study was to define the frequency of Fabry disease among Korean men with LVH.

Methods: In this national prospective multicenter study, we screened Fabry disease in men with LVH on echocardiography. The criterion for LVH diagnosis was a maximum LV wall thickness 13 mm or greater. We screened 988 men with LVH for plasma α-Gal A activity. In patients with low α-Gal A activity (< 3 nmol/hr/mL), we searched for mutations in the α-galactosidase gene.

Results: In seven men, α-Gal A activity was low. Three had previously identified mutations; Gly328Arg, Arg301Gln, and His46Arg. Two unrelated men had the E66Q variant associated with functional polymorphism. In two patients, we did not detect GLA mutations, although α-Gal A activity was low on repeated assessment.

Conclusion: We identified three patients (0.3%) with Fabry disease among unselected Korean men with LVH. Although the prevalence of Fabry disease was low in our study, early treatment of Fabry disease can result in a good prognosis. Therefore, in men with unexplained LVH, differential diagnosis of Fabry disease should be considered.

Keywords: Fabry Disease; Korean Men; Left Ventricular Hypertrophy.

Conflict of interest statement

Disclosure: The Authors have no potential conflict of interest to disclose.

Figures

Fig. 1. Flowchart for the study.
Fig. 1. Flowchart for the study.
α-Gal A = α-galactosidase A.
Fig. 2. Plasma α-Gal A activity in…
Fig. 2. Plasma α-Gal A activity in 986 men with LVH on echocardiography. In seven with LVH (red), values were 0.1 to 2.6 nmol/hr/mL. In the remaining 979 patients with LVH (black), values were 3.0 to 60.7 nmol/hr/mL (mean, 9.4 ± 4.8).
α-Gal A = α-galactosidase A, LVH = left ventricular hypertrophy.
Fig. 3. Renal pathology in Fabry disease.…
Fig. 3. Renal pathology in Fabry disease. (A) Segmental increase of cells and matrix with fuchsinophilic deposits and hyaline globules and markedly enlarged and vacuolated epithelial cells which contain abundant foamy cytoplasm (Toluidine blue stain, magnification, ×80). (B) Immunoglobulin M in the mesangium which is suggestive of a non-specific trapping and tends to exclude an immune-mediated GN (Masson Trichrome stain, magnification, ×400). (C) Glomerulopodocyte containing abundant electron dense myelin figures, Mesangialinsudative deposit with curvilinear microtubular and myelin figures, diffuse foot process effacement and myelin bodies and lysosomes in endothelial cells, smooth muscle cells, tubules and interstitial cells (Electron microscopy, magnification, ×2,500).

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