Cor Vasa 2010, 52(11-12):706-712 | DOI: 10.33678/cor.2010.176

Danon disease - a disorder of autophagy as a cause of hypertrophic cardiomyopathy

Miloš Kubánek^1,*, Milan Elleder², Jakub Sikora^2,3, Marek Šramko¹, Jana Malušková³, Lenka Dvořáková², Hana Vlášková², Martin Kotrč¹, Jana Vrbská¹, Petr Ridzoň⁴, Michal Šnorek⁵, František Toušek⁵, Ivan Málek¹, Jan Pirk⁶

¹ Klinika kardiologie, Institut klinické a experimentální medicíny, Praha

² Ústav dědičných a metabolických poruch, Všeobecná fakultní nemocnice a 1. lékařská fakulta Univerzity Karlovy, Praha

³ Oddělení klinické a transplantační patologie, Institut klinické a experimentální medicíny, Praha

⁴ Neurologická klinika, Fakultní Thomayerova nemocnice, Praha

⁵ Kardiologické oddělení, Nemocnice České Budějovice, a. s., České Budějovice

⁶ Klinika kardiovaskulární chirurgie, Institut klinické a experimentální medicíny, Praha, Česká republika

Danon disease is an X-linked disorder caused by a mutation of lysosomal-associated membrane protein 2 (LAMP2). Clinically, the disorder manifests itself mainly as hypertrophic cardiomyopathy, skeletal muscle myopathy or, alternatively, as liver disease. In women, its presentation in organs and severity of the disorder are modified by X-inactivation. The aim of our study was to report the first case of a family with Danon disease diagnosed in the Czech Republic. The diagnosis was initially established in a 27-year-old man with end-stage heart failure secondary to hypetrophic cardiomyopathy and, subsequently, also in the patient's sister and nephew. The diagnosis was based on evidence of an autophagic process in a skeletal muscle biopsy specimen, immunohistochemically demonstrated absence of LAMP2, and evidence of a pathogenic mutation in the respective gene. Findings reported by cardiologists were consistent with the diagnosis of hypertrophic cardiomyopathy with left ventricular outflow tract obstruction, and EKG showing signs of preexcitation. The disorder manifested itself clinically when the patient was 10 years old (and his sister and nephew aged 12 and 8 years, respectively). The patient and his sister were shown to develop left ventricular systolic dysfunction and progression to end-stage heart failure in their thirties. Their condition was successfully managed by heart transplantation. The skeletal muscle involvement in both patients was reflected in increased serum creatine kinase levels.

Keywords: Hypertrophic cardiomyopathy; Danon disease; LAMP2

Published: November 1, 2010  Show citation