A 19-year-old man, previously in good health, was hospitalized for intermittent heart palpitations. There was no family history of cardiomyopathy, arrhythmia, or sudden cardiac death. His sister had died of cirrhosis at age 12 years, but the exact cause of this cirrhosis was unknown. A physical examination showed that this patient was hemodynamically stable. An electrocardiogram (ECG) showed Wolff–Parkinson–White (WPW) syndrome with paroxysmal wide QRS tachycardia (Fig. A and B). An echocardiogram revealed left ventricular wall thickening, suspected hypertrophic non-obstructive cardiomyopathy, and myocardial amyloidosis with an initial septal thickness of 17 mm and a left ventricular wall thickness of 13 mm (Fig. A and B). Pertinent laboratory test results (Table ) included elevated serum concentrations of myo-inositol (667.5 ng/mL, normal < 107 ng/mL), cardiac troponin (CTnI; 0.187 ng/mL, normal < 0.05 ng/mL), creatine kinase-MB (5.40 ng/mL, normal < 4.3 ng/mL), aspartate aminotransferase (262.5 U/L, normal 15–40 U/L), and alanine aminotransferase (136.1 U/L, normal 9.0–50 U/L). During the process of radiofrequency ablation, the patient repeatedly showed atrioventricular block (AVB; Fig. C). However, after 3 radiofrequency ablation procedures, his WPW disappeared, but he continued to show second degree AVB (Fig. D).\nTwo years after radiofrequency ablation, the patient was again hospitalized for palpitations and dizziness. On physical examination, his apical beat was diffuse, his cardiac boundaries were enlarged to the left, and systolic murmurs were heard in the auscultation areas of his bicuspid and tricuspid valves. ECG indicated atrial flutter, WPW, and third-degree AVB (Fig. E and F). An echocardiogram showed that myocardial densification was incomplete, his left atrium and ventricle were enlarged, his left ventricular beat was diffusely weakened, and his systolic function was reduced. His mitral and tricuspid valves showed regurgitation and thickening of the interventricular septum, with a left ventricular diastolic diameter of 68 mm, a left ventricular wall thickness of 9 mm, a septal thickness of 12 mm, and an ejection fraction of 46% (Fig. C and D). Furthermore, cardiovascular magnetic resonance imaging (CMRI) indicated suspected amyloidosis of the cardiac muscle (Fig. ). His laboratory test results had deteriorated since his previous admission, with his serum myo-inositol, creatine kinase-MB, aspartate aminotransferase, and alanine aminotransferase concentrations being higher than before, and his brain natriuretic peptide concentration being elevated (824.0 pg/mL, normal < 100 pg/mL) (Table ). Amyloid cardiomyopathy was excluded by performing relevant laboratory tests and pathological diagnosis of the adipose tissue attached to the walls. Hyperplasia was observed in the fibrous tissue of the dermis, along with widening of the subcutaneous fat lobule space and positive Congo red staining (Fig. ). These results did not support a diagnosis of amyloid cardiomyopathy (Table ), and the transthyretin (TTR) gene was negative. A cardiac resynchronization therapy pacemaker was implanted to relieve the patient's clinical symptoms. Fifteen days later, he returned to our hospital because of a skin infection at the pacemaker implantation site and was given a permanent replacement pacemaker.\nOne month later, the patient was again hospitalized at our institution because of repeated aggravation of heart failure and the appearance of symptoms of restlessness and confusion. No abnormality was found on computed tomography of the head. No improvement was observed after symptomatic treatment, and he died of cardiac arrest.\nSubsequent genetic testing revealed that this patient was hemizygous for a previously unreported deletion mutation (p.Gly221Ilefs∗19) in the LAMP2 gene, confirming the diagnosis of Danon disease (Fig. ). A myocardial biopsy was not performed.
A 23-year-old man had Danon disease from the age of 12 years, when symptoms began, until 23 years old when he succumbed to his disease. He was first admitted to the Affiliated Hospital of Jining Medical University at 12 years old because of transient loss of consciousness with palpitation. He had suffered from a poor ability of physical activity, mild mental retardation, and learning difficulty. Pansystolic murmur along the left lower sternal border was not observed. Echocardiography showed HCM with a maximum left ventricular end-diastolic diameter (LVEDd) of 45 mm, left ventricular posterior wall (LVPW) thickness of 12 mm, maximum interventricular septal (IVS) thickness of 11 mm, and left ventricular ejection fraction (LVEF) of 60%. Electromyography showed normal muscle strength and deep tendon reflexes. He was diagnosed with Danon disease at 13 years of age in Beijing Union Hospital by genetic testing, which showed that he carried a deletion mutation (c.257_258delCC) in exon 3 of the LAMP-2 gene. An endomyocardial biopsy and electron microscopic examination showed autophagic vacuoles. ECG showed type B Wolff–Parkinson–White (WPW) syndrome, a high voltage in the left ventricle, and an inverted T wave (). He then underwent successful ablation in Beijing Union Hospital. He was asymptomatic for the next 3 years.\nAt the age of 17 years, he had persistent palpitations and visited the hospital. ECG () showed an ectopic rhythm, paroxysmal supraventricular tachycardia, complete left bundle branch block, and high voltage in the left ventricle. He switched to sinus rhythm following treatment with propafenone. However, an ECG () showed ventricular premature contraction. At a physical examination, a heaving apical impulse and a grade 4/6 pansystolic murmur along the left lower sternal border were observed. Follow-up echocardiography indicated that left ventricular hypertrophy of the patient progressively worsened (). MRI was performed and showed LGE in the muscular interventricular septum and the front wall of the left ventricle. However, the liver and bilateral gastrocnemius skeletal muscles were negative for LGE (). This process of cardiac hypertrophy was rapidly advancing at this stage.\nIn the next 4 years, HCM progressed to the dilated phase. The LVEDd increased from 44 to 58 mm, while the IVS decreased from 24 to 19 mm and LVPW decreased from 31 to 17 mm. The LVEF was reduced from 60% to 22% (). At the age of 23 years, an ECG () showed atrial fibrillation. An MRI () showed that gadolinium contrast enhancement was visible in the liver, psoas muscle, and bilateral gastrocnemius muscles. These abnormal findings manifested with the classic triad of cardiomyopathy, skeletal myopathy, and intellectual disability in this patient. He received an automatic implantable cardioverter-defibrillator, even after considering a heart transplant, which he refused, and he finally succumbed to his disease with sudden cardiac arrest. Unfortunately, the patient did not undergo an investigation of his device to identify the trigger for cardiac death.\nDuring the 10-year follow-up, pertinent laboratory examination values, including creatine kinase (CK), creatine kinase isoenzyme (CK-MB), hydroxybutyrate dehydrogenase, alanine aminotransferase (ALT), aspartate aminotransferase, and lactic dehydrogenase levels, were considerably elevated (). Echocardiographic data indicated that HCM had progressed into DCM ().