An overview on cardiac involvement in Inborn Errors of Metabolism: from clinical clues to nutritional management strategies

Chiara Montanari^1,2*Veronica Maria Tagi^1,2Martina Tosi^1,3Eliana Stucchi¹Eleonora Maria Pisano¹Irene Raso⁴Giulia Fini⁴Laura Fiori¹Savina Mannarino⁴Gianvincenzo Zuccotti^1,2Elvira Verduci^1,3

• ¹Department of Pediatrics, Vittore Buzzi Children's Hospital, Milan, Italy
• ²Department of Biomedical and Clinical Science, University of Milan, Milan, Italy
• ³Department of Health Sciences, University of Milan, Milan, Italy
• ⁴Pediatric Cardiology Unit, "Vittore Buzzi" Children's Hospital, Milan, Italy

Inborn errors of metabolism (IEMs) account for a significant proportion of cardiomyopathies presenting with a wide spectrum of cardiac involvement, from isolated manifestations to multisystem syndromes. The manuscript explores the primary forms of cardiac complications linked to various IEMs, underlining the pathophysiological mechanisms and proposing a diagnostic framework guided by specific clinical features. Early diagnosis, especially in forms not captured by newborn screening, relies on careful clinical and metabolic evaluation. Thus, a multidisciplinary approach to address IEMs is essential, with the paediatric cardiologist contributing to both differential diagnosis and treatment. In addition, this review examines nutritional strategies for managing patients affected by IEMs with cardiac involvement, providing clinicians with research-backed guidance to support cardiological care, since specific nutritional strategies have shown promise in reversing or improving cardiac function in specific IEMs. Further research is needed to clarify the long-term safety of dietary interventions, particularly in pediatric populations, and to better define the role of nutrition in managing cardiomyopathies associated with IEMs, in order to develop evidence-based clinical protocols.