Inborn Errors of Metabolism

Excerpt

Inborn errors of metabolism (IEM) constitute a diverse group of congenital disorders caused by pathogenic or likely pathogenic variants in genes coding for enzymes, transporters, or cofactors essential for metabolic pathways. These defects lead to the accumulation of toxic substrates or a deficiency of essential products, disrupting the metabolism of carbohydrates, fatty acids, proteins, or complex molecules. While individual disorders are rare, collectively, IEMs are significant, with an estimated incidence of approximately 1 in 15,000 to 1 in 2 million live births. Clinical presentation varies widely, ranging from acute, life-threatening metabolic crises in the neonatal period to insidious, late-onset manifestations in adulthood. Early recognition and diagnosis are critical, as timely intervention can prevent morbidity and mortality.