Abstract / Summary
Long-chain fatty acid oxidation disorders (LC-FAOD) are rare inherited defects of mitochondrial β-oxidation that impair energy generation during fasting or metabolic stress. Clinical manifestations range from neonatal hypoketotic hypoglycemia and cardiomyopathy to hepatopathy, recurrent rhabdomyolysis, and chronic myopathy. Although newborn screening (NBS) enables early detection, management remains inconsistent due to limited evidence, broadening phenotypic spectrum, and regional practice variation. An international multidisciplinary workgroup of 34 members, including clinicians, nurses, dietitians, and patient representatives, systematically reviewed the literature (1990-2022) using PubMed, Embase, and Web of Science. Evidence was graded using an adapted Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach, and consensus was achieved through a modified Delphi-Nominal Group-Delphi methodology, with agreement defined as ≥ 75%. Especially when evidence was low, expert consensus was the basis for this guideline. Recommendations address diagnosis, dietary management, fasting tolerance, use of medium-chain fat sources, exercise and illness protocols, pregnancy care, and long-term monitoring. Evidence quality ranged from very low to moderate. Strong consensus was reached for critical clinical interventions. Standardized approaches for diagnostic work-up, management during metabolic stress, and follow-up monitoring were developed to promote uniform care across age groups, disease groups, and phenotypic severity. This international guideline integrates available evidence and expert consensus to provide standardized recommendations for diagnosis, treatment and lifelong management of LC-FAOD. They aim to harmonize clinical practice, improve patient outcomes, and support global implementation of evidence-based metabolic care.