Danon disease is a rare X-linked dominant disorder caused by mutations in the lysosome-associated membrane protein-2 (LAMP2) gene.
Clinicallycharacterized by a triad of clinical features: hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability.
Its pathogenesis of Danon disease involves a deficiency in LAMP-2.
Lysosome-associated membrane protein-2 (LAMP2) gene is crucial for autophagy, a cellular process for degrading and recycling cellular components.
Lysosome-associated membrane protein-2 (LAMP2) gene absence or dysfunction of LAMP-2 leads to the accumulation of autophagic vacuoles, particularly affecting cardiac and skeletal muscle tissues.
Male patients with Danon’s disease typically present with severe hypertrophic cardiomyopathy, often associated with Wolff-Parkinson-White syndrome or other conduction abnormalities, and have a median age of death or cardiac transplantation between 19 to 21 years.
Female patients exhibit a broader age range of findings and generally have a milder course, although they can still experience significant cardiac issues and heart failure.
Diagnosis:genetic testing for LAMP2 mutations and can be supported by histopathological findings of autophagic vacuoles in muscle biopsies.
Cardiac magnetic resonance imaging (MRI) can also aid in the diagnostic work-up by revealing characteristic features of the disease.
Management primarily involves symptomatic treatment, including the use of implantable cardioverter-defibrillators for arrhythmias and heart transplantation for advanced cardiac disease.
Gene therapy targeting LAMP2B is under investigation and shows promise in early clinical trials: RP-A501 associated with cardiac LAMP to expression and evidence of clinical improvement over a period of 24 to 54 months.