PMC8215120_01
Patient 1: Chest X-ray showed an enlarged heart (the cardiothoracic ratio reached about 0.65) (a) and echocardiography indicated hypertrophic non-obstructive cardiomyopathy (b). ECG showed sinus tachycardia, short PR interval, biventricular hypertrophy, and multi-lead ST segment changes (c). Follow-up for 8 months, chest X-ray indicated the CTR was 0.65 (d). Echocardiography showed the thickness of IVS and LVPW were 9 and 11 mm, respectively, with no outflow obstruction, and LVEF was 60% (e). ECG revealed multiple lead ST-T changes and left ventricular hypertrophy (f). Patient 2: Echocardiography showed the thickness of interventricular septum (IVS) and left ventricular posterior wall (LVPW) were 9 and 10 mm, respectively (g). ECG revealed left ventricular hypertrophy and multiple lead ST-T changes (h). The asterisk represents IVS and triangle represents LVPW.
fped-09-639687-g0001.jpg
PMC8215120_02_fped-09-639687-g0001.jpg
F1
The good part is that the cardiomyopathy is not progressive which echocardiography showed a septal thickness of 9 mm and posterior wall thickness of 10 mm (Figure 1g). ECG revealed left ventricular hypertrophy and multiple lead ST-T changes (Figure 1h).
Molecular study of the genomic DNA of patient 1 detected a novel AGK homozygous mutation (c.1131 + 2T>C) in the proband (a). Both parents were confirmed to be heterozygous carriers (b,c).
fped-09-639687-g0002.jpg
PMC8215120_01_fped-09-639687-g0002.jpg
F2
Both parents were unaffected and further Sanger sequencing indicated that both the parents were heterozygous for this change (Figure 2).
HE staining showed that the muscle fibers were slightly different in size, and the small fibers were mostly small round and polygonal in shape. Cavitation and fissures were observed in the fibers with most fibers deeply staining the sarcolemma (a) (red short arrow, bar 20 mum). Modified Gomeri tricolor (MGT) staining displayed a large number of muscle fibers showing cytoplasmic and sub-sarcolemma vacuole fissures with RRF-like changes (b) (yellow short arrow, bar 20 mum). Deep staining was seen under the sarcolemma in many fibers in nicotinamide adenine dinucleotide (NAD) (c) (white short arrow, bar 20 mum), succinate dehydrogenase (SDH) (d) (red long arrow, bar 20 mum), cytochrome c oxidase (COX) staining (e) (yellow long arrow, bar 20 mum). The glycogen content of a small number fibers increased significantly with periodic acid Schiff (PAS) staining (f) (white long arrow, bar 20 mum). Transmission electron microscopy (TEM) showed an increased number of lipid droplets in many fibers (g) (red arrowhead, bar 500 nm) and the mitochondria were abnormal with a severe loss of cristae (h) (yellow arrowhead, bar 200 nm).
fped-09-639687-g0003.jpg
PMC8215120_01_fped-09-639687-g0003.jpg
F3
HE stain showed that the muscle fibers were slightly different in size, and the small fibers were mostly small round and polygonal in shape (Figure 3a). Modified Gomeri tricolor (MGT) stain displayed a large number of muscle fibers showing cytoplasmic and sub-sarcolemma vacuole fissures with RRF-like changes (Figure 3b). Deep staining was observed for sarcolemma in many fibers with nicotinamide adenine dinucleotide (NAD), succinate dehydrogenase (SDH), and cytochrome c oxidase (COX) staining (Figures 3c-e). Furthermore, the content of glycogen of a small number of fibers increased significantly with periodic acid Schiff (PAS) staining and the content of lipid droplets in a large number of fibers markedly increased in oil red (ORO) staining (Figure 3f). Transmission electron microscope (TEM) revealed an increased number of lipid droplets in many fibers and the mitochondria were abnormal with a severe loss of cristae (Figures 3g,h).
PMC8215120_02
Patient 1: Chest X-ray showed an enlarged heart (the cardiothoracic ratio reached about 0.65) (a) and echocardiography indicated hypertrophic non-obstructive cardiomyopathy (b). ECG showed sinus tachycardia, short PR interval, biventricular hypertrophy, and multi-lead ST segment changes (c). Follow-up for 8 months, chest X-ray indicated the CTR was 0.65 (d). Echocardiography showed the thickness of IVS and LVPW were 9 and 11 mm, respectively, with no outflow obstruction, and LVEF was 60% (e). ECG revealed multiple lead ST-T changes and left ventricular hypertrophy (f). Patient 2: Echocardiography showed the thickness of interventricular septum (IVS) and left ventricular posterior wall (LVPW) were 9 and 10 mm, respectively (g). ECG revealed left ventricular hypertrophy and multiple lead ST-T changes (h). The asterisk represents IVS and triangle represents LVPW.
fped-09-639687-g0001.jpg
PMC8215120_02_fped-09-639687-g0001.jpg
F1
The good part is that the cardiomyopathy is not progressive which echocardiography showed a septal thickness of 9 mm and posterior wall thickness of 10 mm (Figure 1g). ECG revealed left ventricular hypertrophy and multiple lead ST-T changes (Figure 1h).