Inborn errors of metabolism – challenge in pediatrics

Abstract

Introduction. Among the 6000 to 8000 recognized rare diseases, more than 1000 are classified as inborn errors of metabolism (IEMs). Collectively, these disorders affect approximately one in every 500 newborns, posing significant diagnostic and management challenges in both general and pediatric medical practice [1-5]. IEMs are caused by the complete or partial absence, or dysfunction, of enzymes, cofactors, structural proteins, or transporter molecules. This results in either the accumulation or deficiency of specific metabolites, disrupting normal metabolic processes being genetically determined. The term „inborn errors of metabolism” was first introduced by British physician Archibald Garrod (1857–1936) in the early 20th century. His pioneering research on Alkaptonuria laid the foundation for the „one gene–one enzyme” hypothesis, marking a seminal moment in the development of medical genetics [2]. The definition of IEMs has remained relevant over time, emphasizing that metabolic disturbances can lead to a spectrum of clinical manifestations ranging from mild to severe. These manifestations frequently include st o ea nd and psychiatric symptoms, other affecting the liver, muscle, kidney or heart, which may result in death or lifelong disability. Although traditionally regarded as pediatric disorders, IEMs can present at any age, including from neonate to adolescence and adulthood [1,2,3].