ABSTRACT
OBJECTIVE: To investigate whether the Ala143Thr variant of the α-galactosidase A gene (A143T/GLA), with conflicting interpretations of pathogenicity, is associated with Fabry cardiomyopathy. METHODS: The index patient, a woman in her 60s with cardiomyopathy, was screened for variants in 59 cardiomyopathy-related genes. A143T/GLA, the only rare variant found, was screened in 10 relatives. GLA activity and lyso-Gb3 levels were measured and echocardiography was performed in 8 of 9 subjects carrying A143T/GLA. Cardiac magnetic resonance (CMR) imaging and 18F-fluorodeoxyglucose (FDG) positron emission tomography/CT (PET/CT) were performed in four adult A143T/GLA carriers. Endomyocardial biopsy was obtained from two adult A143T/GLA carrying sons of the index patient. RESULTS: The index patient and her elder son had a pacemaker implantation because of sick sinus syndrome and atrioventricular block. GLA activities were decreased to 25%-40% of normal in both sons and one granddaughter. Lyso-Gb3 levels were elevated in both sons. In CMR, the index patient and her two sons had left ventricular (LV) hypertrophy and/or dilatation. The elder son had late gadolinium enhancement, high CMR-derived T1 time and positive FDG signal in PET/CT in the basal inferolateral LV wall. The younger son had low T1 time and the mother had positive FDG signal in PET/CT in the basal inferolateral LV wall. Endomyocardial biopsy of both sons showed myocardial accumulation compatible with glycolipids in light and electron microscopy, staining with anti-Gb3 antibody available for the younger son. Five female relatives with A143T/GLA had no cardiomyopathy in cardiac imaging. CONCLUSIONS: A143T/GLA is likely a late-onset Fabry cardiomyopathy causing variant with incomplete penetrance.
Subject(s)
Cardiomyopathies/genetics , DNA/genetics , Mutation , alpha-Galactosidase/genetics , Adolescent , Adult , Aged , Cardiomyopathies/diagnosis , Cardiomyopathies/metabolism , Child , DNA Mutational Analysis , Echocardiography , Female , Genetic Testing , Genotype , Humans , Magnetic Resonance Imaging, Cine/methods , Male , Middle Aged , Pedigree , Positron Emission Tomography Computed Tomography , Young Adult , alpha-Galactosidase/metabolismABSTRACT
BACKGROUND: Respiratory motion (RM) complicates the analysis of myocardial perfusion (MP) single-photon emission computed tomography (SPECT) images. The effects of RM on left ventricular (LV) functional variables have not been thoroughly investigated. METHODS AND RESULTS: Thoracic electrical bioimpedance and electrocardiographic signals were recorded from eighteen patients undergoing the rest phase of a 1-day stress/rest cardiac-gated MP-SPECT examination. The signals and list-mode emission data were retrospectively processed to yield standard cardiac- and dual-gated (respiratory and cardiac gating) image sets applying a novel algorithm. LV volume, MP, shape index (SI), wall motion (WM), wall thickening (WT), and phase analysis parameters were measured with Quantitative Perfusion SPECT/Quantitative Gated SPECT software (Cedars-Sinai Medical Center). Image quality was evaluated by three experienced physicians. Dual gating increased LV volume (77.1 ± 26.8 vs 79.8 ± 27.6 mL, P = .006) and decreased SI (0.57 ± 0.05 vs 0.56 ± 0.05, P = .036) and global WT (39.0 ± 11.8% vs 36.9 ± 9.4%, P = .034) compared to cardiac gating, but did not significantly alter perfusion, WM or phase analysis parameters or image quality (P > .05). CONCLUSIONS: RM reduction has an effect on LV volume, shape, and WT parameters. RM exerts no significant effect on phase analysis parameters.
