Danon disease

Danon disease is a lysosomal glycogen storage disorder that primarily affects the heart and skeletal muscles, and it is frequently associated with cognitive impairment. It results from pathogenic variants in the LAMP2 gene, which is important for lysosomal function and cellular waste processing. As an X‐linked dominant condition, affected males often experience more severe manifestations while affected females may display a range of symptoms. This condition is very rare, affecting fewer than 1 in 1,000,000 people.

Individuals with Danon disease typically present with a constellation of features affecting multiple organ systems. Cardiac manifestations such as severe cardiomyopathy, congestive heart failure, dilated or hypertrophic cardiomyopathy, and various arrhythmias including Wolff-Parkinson-White syndrome are characteristic and contribute substantially to the clinical picture. Muscular issues include pronounced muscle weakness, muscle flaccidity, gait disturbances, and elevated circulating creatine kinase levels, while skeletal muscle autophagosome accumulation is also invariably seen. In addition, many affected individuals experience intellectual disability, highlighting central nervous system involvement. Not all individuals experience all features, and severity varies considerably.

Danon disease is caused by pathogenic variants in the LAMP2 gene, which plays a key role in lysosomal function and autophagy. The disorder is inherited in an X-linked dominant pattern, meaning that males typically manifest more severe symptoms compared to females, who may experience milder or more variable features due to differences in X-inactivation. Although a de novo origin is not specifically stated, the inheritance pattern underscores the risk of passing the condition on, making genetic counseling an important step for affected families seeking guidance on family planning.

Currently, management of Danon disease focuses on supportive care and symptom management, as there are no FDA-approved treatments specifically for this condition. Treatment is highly individualized and involves a multidisciplinary team to address the cardiac, muscular, and cognitive aspects of the disease. Regular surveillance, particularly with cardiac monitoring such as echocardiograms, is an essential part of long-term care, helping to detect emerging complications early. Patients and families are encouraged to discuss treatment options with their healthcare team, including the potential role of investigational therapies under clinical trials, and to consider genetic counseling as part of their care plan.

The prognosis for individuals with Danon disease is variable and depends on the severity of cardiac, muscular, and cognitive manifestations as well as the age at diagnosis and access to specialized care. With current standards of care, many individuals live into adulthood despite the significant challenges associated with the condition. Outcomes described in medical literature continue to evolve as standards of care improve. Families are advised to connect with specialists and genetic counselors for ongoing guidance and supportive care, as the course of the disease can vary significantly between individuals.

Clinical trials are underway exploring new treatment approaches for Danon disease. Individuals interested in clinical trials can search ClinicalTrials.gov or consult their healthcare team to learn more about eligibility for ongoing studies.