A Multinational Study of Patient and Caregiver-Reported Insights Into ADSS1 Myopathy

Adenylosuccinate synthase-like 1 (ADSS1) myopathy is an ultra-rare disorder caused by biallelic pathogenic variants in the ADSS1 gene. This results in progressive muscle weakness, fatigue, dysphagia, and, in severe cases, cardiomyopathy and respiratory failure. The aim of the study was to evaluate how ADSS1 myopathy impacts patients' lives and to comprehensively assess their quality of life.

We conducted individual interviews in 31 participants with ADSS1 myopathy from six countries. Participants engaged in structured interviews, which included both open-ended questions and the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. Thematic analysis was employed to identify the primary concerns, symptoms, and quality-of-life challenges faced by patients.

From individual interviews, the decline in mobility and motor skills (54.8%) and muscle weakness (48.3%) primarily impacting the lower extremities emerged as the most frequently reported bothersome symptoms. The most reported concerns were decline in mobility, motor skills, and gait disturbance (58.0%). Only 5% of the patients reported no impact of ADSS1 myopathy on their work or social life. The INQoL questionnaire identified 20 patients (64.5%) with pain, with the most common location being the lower extremities, while fatigue was reported by all patients except one. The most identified treatment priorities were improving motor function (51.6%) and halting disease progression (48.3%).

This study highlights the significant physical and psychosocial burden of ADSS1 myopathy, with progressive muscle weakness and multisystem involvement affecting daily life. The findings underscore the need for early diagnosis and multidisciplinary care approaches.