2022 Volume 86 Issue 9 Pages 1479-
A 54-year-old Japanese woman was admitted because of heart failure. She had been blind since 37 years of age because of central retinopathy, and had undergone surgery for breast cancer at 45 years of age. She had no family history of cardiomyopathy and neither the patient nor her family had any symptoms suggestive of Fabry disease (FD; e.g., acroparesthesia, hypohidrosis, angiokeratoma, renal dysfunction, or stroke).
Laboratory data were normal except for high N-terminal pro B-type natriuretic peptide (2,484 pg/mL) and high sensitive troponin T (0.077 ng/mL) levels. Electrocardiography showed sinus rhythm and an abnormal Q wave in leads II, III, aVF, and V4–6. Echocardiography demonstrated left ventricular (LV) hypertrophy with a dyskinetic thinned LV apex (ejection fraction 46%; Figure A,B). Cardiac magnetic resonance imaging demonstrated late gadolinium enhancement in the posterolateral apical region of the LV (Figure C). Because coronary angiography was normal, an endomyocardial biopsy was performed. Microscopy demonstrated myocardial hypertrophy and disarray with cytoplasmic vacuolation in the myocytes (Figure D). Electron microscopy revealed myelin figures in the myocytes (Figure E). Although leukocyte α-galactosidase A (GLA) activity was slightly low (14 nmol/mg/h; control range 17–65 nmol/mg/h) and the plasma lyso-globotriaosylsphingosine concentration was high (19 nmol/L; control range 0.31–0.75 nmol/L), no mutations were detected by a gene analysis covering 7 exons, intron/exon boundaries, and the specific intronic region containing IVS4+919 of the GLA gene. Globotriaosylceramide (Gb3) immunostaining was performed using an anti-Gb3 mouse monoclonal antibody with myocytes staining positive (Figure F). Finally, the patient was diagnosed with FD. Immunostaining for Gb3 is important for the diagnosis of approximately 5% of FD patients.
Transthoracic echocardiography: (A) end-diastolic phase; (B) end-systolic phase, apical 4 chamber view. (C) Gadolinium-enhanced cardiac magnetic resonance image. (D) Microphotograph of the biopsied myocardium (hematoxylin and eosin staining). (E) Electron microscopy revealed myelin figures in the myocytes. (F) Immunostaining for globotriaosylceramide (red) revealed globotriaosylceramide-positive myocytes (arrows). (G) Negative control.
The authors declare no conflicts of interest.
