Multicenter retrospective cohort study reveals clinical trajectories and potential biomarkers in MT-ATP6/8 deficiency, highlighting phenotypic variability across age groups.
Key Points
To describe the retrospective natural history of patients harboring pathogenic MT-ATP6 and MT-ATP8 variants and identify endpoints and biomarkers for future clinical trials.
International multicenter retrospective cohort study collecting data across national reference centers and registries in Italy, Germany, Spain, and the United States.
Infantile and pediatric patients demonstrated significantly reduced survival compared with adult patients (p = 0.0349), with an overall mortality rate of 8% at final follow-up and 11% requiring wheelchairs.
The central nervous system was affected in 93% of patients, presenting isolated Leigh-like lesions on brain MRI in 58%, followed by involvement of muscle (75%), eyes (46%), and heart (18%).
Genetic evaluation identified 26 pathogenic variants (6 novel), alongside common metabolic abnormalities including elevated lactate (71%), reduced citrulline (56%), and elevated alanine (49%).