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].