GENETIC BASIS, CLINICAL MANIFESTATIONS, AND MODERN DIAGNOSTIC APPROACHES TO INHERITED METABOLIC DISEASES IN CHILDREN

Inherited metabolic diseases (IMDs), also known as inborn errors of metabolism, comprise a heterogeneous group of genetic disorders caused by defects in enzymes, transport proteins, receptors, cofactors, or other components of cellular metabolic pathways. Although each individual condition is rare, collectively these diseases represent an important cause of neonatal and pediatric morbidity, neurodevelopmental impairment, recurrent metabolic decompensation, organ dysfunction, and preventable mortality. The clinical spectrum ranges from acute life-threatening neonatal encephalopathy to slowly progressive neurological, hepatic, cardiac, muscular, or multisystem disease. Early recognition is therefore essential because a considerable number of IMDs are treatable when therapy is initiated before irreversible tissue damage occurs. Modern diagnostic strategies combine careful clinical assessment with biochemical tests, tandem mass spectrometry, chromatography, enzymatic assays, targeted molecular testing, next-generation sequencing, whole-exome or whole-genome sequencing, and expanded newborn screening. This thesis summarizes the genetic basis of common pediatric IMDs, their major clinical manifestations, and contemporary diagnostic approaches, with emphasis on early detection and the integration of biochemical and molecular-genetic methods into pediatric practice [1-8].