Introduction

Danon disease is a severe, rare, and progressive X-linked dominant metabolic disorder.^1,2 Learning and cognitive disorders were found in most or all of the male population studied of Danon disease patients and in about half of the female population. For women, heart disease is the most common symptom, while it is the second most common for men; however, it is reported more frequently by men than by women.^1,2 

Unlike common diseases with established treatment protocols, rare diseases like Danon disease rely heavily on patient experience to guide clinical decisions. The multisystem nature means that seemingly minor symptoms significantly impact daily functions in ways that conventional assessments might miss. As therapeutic options expand, understanding what outcomes matter most to patients becomes essential for evaluating treatment effectiveness. 

This article will examine patient-reported outcomes (PROs) and quality of life (QoL) in Danon disease, identify key impact factors, and provide recommendations for improving clinical care and research. 

Danon disease: Clinical background

Danon disease is characterised by severe cardiomyopathy, skeletal myopathy, and cognitive impairment. The cardiac manifestations are typically the most severe and predominant, while the other areas can vary significantly in predominance and severity among the affected population.³

The multisystem nature of the disease manifests through symptoms and signs in various physiological systems ³ 

• Cardiac: severe and progressive cardiac hypertrophy, arrhythmias
• Skeletal: muscle weakness, myalgias
• Neurocognitive: learning disabilities, mild cognitive deficits
• Psychiatric: anxiety, mood disorders
• Visual: retinopathy
• Gastrointestinal: hepatomegaly, elevated liver enzymes

Danon disease diagnosis is generally based on a family history of cardiomyopathy with an X-linked hereditary pattern and multiorgan dysfunction;³ however, it is necessary to implement confirmatory genetic testing for the final diagnosis.³

There are currently no therapies available to treat Danon disease; therefore, a multidisciplinary care approach, including specialists in cardiology, neurology, genetics, ophthalmology, rehabilitation medicine, and physical therapy, is preferred to alleviate the effects of the disease on patients and their families.⁴ 

When the final stages of cardiomyopathy arrive, a cardiac transplantation may be necessary. The prognosis of this intervention is especially favourable in women, and outcomes are good despite the involvement of extracardiac symptoms.⁵

Genetic therapies for Danon disease are being developed to address the underlying abnormalities of the condition.⁶ 

While initial therapies had limited success, innovative alternatives have provided hope.⁷

Patient-reported outcomes and quality of life in danon disease

PROs and QoL in Danon disease are increasingly considered very important endpoints, especially with the development of new, more innovative therapies targeting the disease. 

A recent clinical trial for Danon disease included assessments of PROs and QoL as exploratory endpoints, and the study found that patients who received gene therapy showed clinical improvements, including stabilisation or reduction of heart failure symptoms and preservation of heart function, which could likely have a positive impact on QoL. However, detailed results on the qualitative outcomes were not provided in the summary, indicating a gap in comprehensive reporting and the need to address them in further studies.⁸

The symptoms associated with Danon disease can affect everyday activities and overall well-being. Although both men and women face high rates of complications, men tend to have an earlier onset and a more pronounced multisystem involvement, which further negatively impacts their QoL.⁹

While clinical outcomes and disease progression are well represented and documented, there is a gap in the presence of detailed and validated PROs measures and QoL data that are specific to Danon disease.^8,9 

Key factors impacting quality of life in danon disease

• Physical symptoms such as muscle weakness, cardiac symptoms, pervasive fatigue, and pain
• Cognitive and neuropsychiatric issues such as learning difficulties affecting educational achievement, mood disorders, behavioural challenges, and sleep disturbances
• Treatment burden significantly impacts quality of life through frequent monitoring and psychological burden

Patient reported outcomes in rare diseases

A broader overview of outcome measures for rare diseases could provide a clearer picture of the future work needed to understand the condition better. However, the lack of data and instruments for measuring PROs in Danon poses a significant challenge. Rare diseases can lead to significant reductions in QoL for patients affected by these condition and their families, making it necessary to ensure that their voices are central to clinical decisions. It is also the key to understanding and evaluating the efficiency of therapeutic interventions.PROs are used to capture the population affected by the disease's view of their health status and to facilitate understanding of the impact the disease and its treatment have on the patient’s QoL and symptoms. 

Strategies to improve QoL in danon disease

• Multidisciplinary management, requires coordinated care from multiple specialists, understanding both individual expertise and broader disease context. Care coordination by professionals who are familiar with Danon disease (DD) reduces family burden while ensuring comprehensive care
• Psychological support, including individual and family counseling, support groups, and mentorship programs connecting newly diagnosed families with experienced ones
• Patient advocacy organisations provide reliable information, facilitate patient connections, advocate for better understanding, and drive patient-centred research agendas through registries and funding priorities

Future directions

There is a substantial gap in the availability of longitudinal QoL data, a poorly characterised natural history of PROs, a lack of intervention studies focused on QoL, and a lack of multicultural and pediatric research. Global registries are critically needed for international collaboration, systematic collection of clinical data, and PROs using standardised instruments. Clinical trials should incorporate PROs as one of the main endpoints, recognising that QoL improvements in rare diseases may be as important as clinical measures. 

Summary 

This examination reveals substantial QoL challenges faced by Danon disease patients and families, alongside significant gaps in understanding their experiences. QoL impairment is multidimensional, affecting physical functioning, psychological health, social relationships, and independence, while extending to family functioning and caregiver wellbeing. 

Focusing on the patient’s perspective in Danon disease management is essential as traditional clinical measures capture only part of the disease impact that matters to patients. PROs offer pathways to patient-centred care and research, enabling clinicians to understand the disease better while guiding researchers to address what matters most to patients.

The ultimate goal is to improve the lives of patients and families affected by Danon disease. While curative treatments remain elusive, significant improvements in QoL are achievable through a better understanding of patient experiences and systematic approaches to addressing their priorities and concerns. In rare diseases where every patient’s journey is unique, listening to and learning from the patient’s voice isn’t just good practice; it is essential for a meaningful process.