Enfermedad de Danon

Abstract

Danon disease is a multisystem disorder clinically characterized by hypertrophic cardiomyopathy, skeletal myopathy and mental retardation in male patients, and by a milder phenotype (predominantly involving cardiac muscle) in female patients. The primary deficiency of lysosome-associated membrane protein-2 (LAMP-2) causes disruption of autophagy, leading to an impaired fusion of lysosomes to autophagosomes and biogenesis of lysosomes Danon disease is inherited as an X-linked dominant trait. At echocardiography, the cardiomyopathy typically manifested as a concentric LV hypertrophy, with preserved ejection fraction, especially in childhood, but later progressed to a dilated pattern. Skeletal myopathy was present in 80-100% of patients, usually in a mild form but occasionally severe. Mild to moderate learning or cognitive disabilities were found in 70-100% of patients. In females, cardiac symptoms usually began in adolescence or adulthood and were slower to progress than in males. Targeted next-generation sequencing provides a rapid, simple, and very sensitive screening method for the early detection of LAMP-2 gene mutations. An early diagnosis plays a fundamental role in the primary prevention of sudden death, such as ICD implantation and timely heart transplantation. In male patients, the prognosis is poor due to rapid progression towards heart failure, and only heart transplantation modifies the disease course. Since intellectual disability and skeletal myopathy are mild and not life-threatening, prognosis after heart transplantation is good.