An Unusual Clinical Presentation of Danon Disease in a Female

Abstract

<h3>Introduction</h3> Danon disease is a rare X-linked dominant skeletal and cardiac muscle disorder with multisystem clinical manifestations caused by mutations in the <i>LAMP2</i> gene. <i>LAMP2</i> mutations are identified in unselected cardiomyopathy cohorts in <0.3% of cases. We report a patient with Danon cardiomyopathy and no skeletal muscle involvement who underwent successful left ventricular assist device (LVAD) implantation. <h3>Case Report</h3> A 39-year-old patient with stage D heart failure (HF) and a LV ejection fraction of 20%, paroxysmal atrial fibrillation, Wolf-Parkinson-White (WPW) syndrome, and type 2 diabetes mellitus was admitted with decompensated HF. There was no family history of cardiomyopathy or sudden cardiac death. She was diagnosed with HF 4 years prior at that time she had concentric LV hypertrophy (interventricular septal thickness 1.4 mm) and LV end diastolic diameter of 5 cm. A cardiac PET did not identify any areas of ischemia and no FDG uptake to suggest active sarcoidosis. Left heart catheterization revealed angiographically normal coronary arteries. Genetic testing identified a heterozygous deletion in <i>LAMP2</i> (5'UTR_3'UTRdel), resulting in complete deletion of 1 allele. She was started on inotrope therapy due to low cardiac output but deteriorated due to incessant ventricular arrhythmias. She underwent HeartMate 3 (HM3) LVAD implantation as a bridge to heart transplant. The LV apical core biopsy revealed vacuolated and hypertrophic cardiomyocytes with endocardial fibrosis, consistent with Danon disease. In 6 months since surgery, she is doing well without LVAD-related complications. She was referred to genetic counseling and her now 10 years old daughter is being genetically tested. <h3>Summary</h3> This case reports an unusual clinical presentation of severe HF due to Danon disease in a female. She had primary myocardial involvement with WPW and mild learning disability but had no skeletal muscle or retinal involvement. Because of the X-linked nature of the disease, males are more severely affected, though progression to advanced HF has rarely been reported in females. This case highlights the importance of genetic testing for cardiomyopathies and subsequent genetic counseling of family members.