Recent advances in adult-onset disorders of muscle lipid metabolism

To summarize recent advances in adult-onset disorders of muscle lipid metabolism, with particular emphasis on fatty acid β-oxidation disorders (FAODs), multiple acyl-CoA dehydrogenase deficiency (MADD) and MADD-like disorders, and neutral lipid storage disease with myopathy (NLSDM).

Recent studies in FAODs have provided new insights into long-term outcomes, exercise physiology, prognostic biomarkers, and the impact of newborn screening (NBS) on disease management. In MADD, growth differentiation factor 15 (GDF15) has emerged as a potential biomarker. Major advances have occurred in MADD-like disorders, including the identification of COASY as a novel disease gene and the recognition of sertraline-associated acquired MADD-like disorder, challenging the traditional view of FAODs as exclusively genetic diseases. In NLSDM, recent cohort studies have expanded the phenotypic spectrum, highlighted cardiomyopathy as a major determinant of morbidity and mortality, and revealed a critical role of adipose triglyceride lipase (ATGL) in maintaining mitochondrial network integrity and function.

Advances in clinical phenotyping, metabolic biomarkers, molecular genetics, and NBS have substantially improved the diagnosis and understanding of adult-onset disorders of muscle lipid metabolism. The recognition of sertraline-associated MADD-like disorder has established that lipid storage myopathies can also arise through acquired toxic mechanisms. Collectively, these developments are expected to facilitate earlier diagnosis, improve disease classification, and support the development of targeted therapeutic strategies for these rare but often treatable disorders.