An eight-year-old Hispanic boy presented with persistent palpitations. Past medical history included asthma, myopia, hypothyroidism, and speech delay. Family history was unremarkable for muscular dystrophies, cardiomyopathy, arrhythmias, or sudden cardiac death. On physical examination, he was hemodynamically stable. A grade 3/6 pansystolic murmur along the left lower sternal border was appreciated. Interestingly, no skeletal muscle disease was appreciated as the patient had 5/5 strength present bilaterally in upper and lower extremities.\nPertinent labs () included elevated brain natriuretic peptide (average 5228 ± 3660 pg/mL; normal <100 pg/mL), elevated creatine kinase (average 649 ± 105 U/L; normal 94–499 U/L), elevated AST (average 363 ± 44 U/L; normal 10–40 U/L), and elevated ALT (average 225 ± 47 U/L; normal 7–56 U/L) levels. No troponin levels were reported. Electrocardiogram (ECG) showed a Wolf-Parkinson-White (WPW) with a left bundle branch block pattern, and peaked QRS complexes consistent with hypertrophic cardiomyopathy (). Echocardiogram revealed hypertrophic cardiomyopathy (HCM) with initial septal thickness of 26 mm.
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.