Muscular dystrophinopathies, particularly Becker Muscular Dystrophy (BMD) and Duchenne Muscular Dystrophy (DMD), are X-linked recessive disorders caused by dystrophin gene mutations. A key difference lies in protein expression, where DMD is characterised by a complete absence of functional dystrophin, leading to rapid and severe muscle degeneration, while BMD produces partially functional dystrophin, resulting in milder symptoms and slower progression. Investigating the key metabolic pathways in DMD and BMD may reveal substantial disruptions in energy metabolism, shedding light on the pathophysiological mechanisms behind muscle damage and metabolic inefficiencies. Our hypothesis posits that urinary metabolites associated with muscle energy could effectively assess disease severity.
Current research investigates metabolic biomarkers in bodily fluids to enhance understanding of these conditions while avoiding invasive procedures. This study explores on global metabolomics of BMD (severe, mild, control) and DMD (disease vs. age-matched control) using serum and urine samples. Results revealed 19,744 identified metabolites, with 4,963 significantly associated with disease severity. Notable metabolites, including phosphatidylcholine, phosphatidylserine, sphingomyelin, sphingosine, and carnosine, highlight disrupted metabolic pathways. The creatine-to-creatinine ratio emerged as a key focus of this study, showing significantly higher values in patients with the disease compared to controls. This increase was particularly pronounced in severe BMD cases, strongly correlating with disease severity. Metabolomic profiling in DMD patients revealed similarly elevated ratios compared to age-matched healthy controls, highlighting its potential as a biomarker. The ratio reflects muscle energy metabolism and degradation, serving as a sensitive indicator of disease severity and muscle preservation or breakdown. Its consistent specificity in both urine and serum underscores its clinical utility, while robust sensitivity and strong correlation with disease severity make it a valuable tool for monitoring disease progression and evaluating therapeutic efficacy in both DMD and BMD.