D‐ and L‐Amino Acid Blood Concentrations Are Affected in Children With Duchenne Muscular Dystrophy

• Published in: Journal of cellular and molecular medicine Vol. 29; no. 9; pp. e70495 - n/a
• Main Authors: Garofalo, Martina, Panicucci, Chiara, Imarisio, Alberto, Nuzzo, Tommaso, Brolatti, Noemi, De Stefano, Maria Egle, Valente, Enza Maria, Errico, Francesco, Bruno, Claudio, Usiello, Alessandro
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2025; John Wiley and Sons Inc
• Subjects: Adolescent; Ambulatory assessment; Amino acids; Amino Acids - blood; Asparagine; Attention deficit hyperactivity disorder; biomarker; Biomarkers; Biomarkers - blood; Biosynthesis; Body composition; Body mass index; Case-Control Studies; Child; Child, Preschool; Children; Chromatography; Chromatography, High Pressure Liquid; Cognition & reasoning; Cognitive ability; Creatine; Creatine kinase; Creatinine; Dual energy X-ray absorptiometry; Duchenne muscular dystrophy; Duchenne's muscular dystrophy; Dystrophin; D‐aspartate; D‐serine; Energy metabolism; Enzymes; Female; glutamate; Glutamic Acid - blood; Glutamine; Glutamine - blood; High-performance liquid chromatography; Humans; Intelligence; Kinases; Male; Metabolism; Metabolomics; motor dysfunction; muscle wasting; Muscle, Skeletal - metabolism; Muscular dystrophy; Muscular Dystrophy, Duchenne - blood; Neuropsychology; Neurotransmission; Original; Pathogenesis; Pediatrics; Serine; serum; Skeletal muscle; D‐serine; Duchenne muscular dystrophy; amino acids; motor dysfunction; biomarker; serum; D‐aspartate; glutamate; muscle wasting
• ISSN: 1582-1838; 1582-4934; 1582-4934
• DOI: 10.1111/jcmm.70495

ABSTRACT Duchenne muscular dystrophy (DMD) is an X‐linked disease caused by the absence of functional dystrophin in the muscle cells. Recent untargeted metabolomics studies identified amino acid metabolism alterations as biochemical pathways potentially involved in DMD pathogenesis. Here, in a well‐characterised cohort of DMD children and paediatric controls, we investigated by high‐performance liquid chromatography (HPLC) the serum profile of a selected pool of amino acids in D‐ and L‐configuration, including L‐glutamate, L‐glutamine, glycine, L‐aspartate, D‐aspartate, L‐asparagine, L‐serine, and D‐serine. These amino acids are known to modulate neurotransmission and to play essential roles in energy and skeletal muscle metabolism. HPLC determinations highlighted a general amino acid deregulation in DMD compared to controls, including lower levels of L‐aspartate, L‐asparagine, D‐serine, L‐glutamine, and glycine and D−/Total serine ratio. In control subjects, we observed a significant positive correlation between L‐glutamine and age, which lacked in affected children. Conversely, in DMD, we observed (i) a negative correlation of L‐glutamate and L‐aspartate with serum creatinine and creatine kinase levels; (ii) a direct correlation of serum L‐glutamine/L‐glutamate ratio with the fat‐free mass index (as determined by dual energy X‐ray absorptiometry) and with specific motor function scores (North Star Ambulatory Assessment); and (iii) no correlations between glucocorticoid treatment or cognitive function and the serum amino acid profile. Our study highlights significant correlations between serum L‐glutamate levels, L‐glutamine/L‐glutamate ratio, and the multidimensional measures of muscle wasting and motor impairment, suggesting that peripheral glutamine‐glutamate metabolism can be a suitable biomarker of disease severity and progression in DMD patients.