Danon disease: Two case reports and literature review

Figures

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  Figure 1.. Pedigree of the family with LAMP2 mutation. II-4 is proband. Black symbols indicate affected subjects, white symbols indicate unaffected subjects. The black arrow indicatesthe proband. LAMP2 = lysosomal-associated membrane protein 2.

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  Figure 2.. Electrocardiogram and echocardiography of the proband aged 15 years. (A) ECG shows sinus rhythm, premature atrial contractions, WPW syndrome. The typical delta wave on the ECG of WPW syndrome (arrows) (B) Echocardiography assessment shows left ventricular hypertrophy. ECG = electrocardiogram, WPW = Wolff–Parkinson–White.

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  Figure 3.. Histological staining of the proband’s skeletal muscle.(A) HE staining showed small vacuoles (arrows) within the muscle fibers containing basophilic particels; (B) Golgi staining showed the absence of RRF and RV in myofibers; (C) PAS staining (d,×400) showed abnormal glycogen granules (arrows) deposition in muscle fiber vacuoles; (D) electron microscopy revealed many glycogen particles deposited in the cytoplasm; (E–G) The staining of ACP, NSE and AchE in vacuoles showed positive results (arrows). (H) Immunohistochemical analysis demonstrated high expression of dystrophin both on myofiber membrane and in vacuoles (arrows); (I) Immunohistochemistry demonstrated only a few intracytoplasmic vacuoles displayed the expression of LAMP2 protein (arrows). AchE = acetylcholinesterase, ACP = acid phosphatase, HE = hematoxylin-eosin, LAMP2 = lysosomal-associated membrane protein 2, NSE = nonspecific esterase, PAS = periodic acid-Schiff staining, RRF = ragged-red fibers, RV = irregular vessels.

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  Figure 4.. The schematic diagram of LAMP2 gene mutation shows that the first G of the intron 6 is replaced by T. LAMP2 = lysosomal-associated membrane protein 2.

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  Figure 5.. The echocardiogram and ECG of the patient. (A) The patient’s first echocardiogram and (B) the rechecked echocardiogram after the patient took the anticoagulant warfarin. The thrombus is pointed to by the red arrow. (C) The patient’s ECG indicates atrial premature beats. ECG = electrocardiogram.

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  Figure 6.. Cardiac magnetic resonance imaging (CMR) of the patient. (A, B) Diffuse thickening of the left and right ventricular myocardium; (C, D) MR first-pass myocardial perfusion imaging showing multiple areas of hypoperfusion in the left ventricular myocardium, suggestive of myocardial ischemia; (E, F) MR delayed-enhancement scanning revealing multiple foci of abnormal enhancement in the left and right ventricular myocardium, indicative of scarring or fibrosis.

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  Figure 7.. Myocardial histological staining of the patient. (A) HE staining and (B) electron microscopy of cardiomyocyte. HE = hematoxylin-eosin.

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  Figure 8.. Histological staining of the patient’s skeletal muscle.(A) HE staining showed many small vacuoles and containing basophilic particels within the muscle fibers; (B) ATP staining demonstrated selective atrophy of type Ⅱ muscle fibers (pH = 10.6); (C) Immunohistochemical analysis using an antibody against dystrophin revealed the presence of dystrophin protein on the membrane of muscle fibers and vacuoles; (D) Immunohistochemistry of skeletal muscle biopsy showed a near absence of LAMP2 protein in muscle fibers. HE = hematoxylin-eosin, LAMP2 = lysosomal-associated membrane protein 2.