Chapter 27: Inborn Errors of Metabolism

Inborn Errors of Metabolism study of biochemical genetics focuses on inborn errors of metabolism (IEM), providing an in-depth analysis of how hereditary gene mutations disrupt essential enzymatic functions and metabolic pathways. The text clarifies the fundamental pathophysiology behind these inherited disorders, where a single enzyme deficiency can cause substrate toxicity, product depletion, or the shunting of metabolites through alternative, often pathological, routes. It emphasizes the clinical necessity of early detection, detailing a wide array of symptoms ranging from neonatal metabolic acidosis and hyperammonemia to chronic intellectual disabilities and hepatosplenomegaly. Extensive coverage is given to screening methodologies, including nationwide neonatal blood-spot programs for phenylketonuria (PKU) and prenatal testing for high-risk families. The chapter systematically categorizes various conditions, such as amino acidopathies like maple syrup urine disease, urea cycle defects, and lysosomal storage disorders including Tay-Sachs and Gaucher disease. Additionally, it explores complex errors in carbohydrate metabolism, such as galactosaemia and the spectrum of glycogen storage diseases like von Gierke and Pompe disease, while also addressing mitochondrial DNA mutations, peroxisomal malfunctions, and pharmacogenetic triggers like G6PD deficiency. Finally, the summary outlines modern therapeutic principles, advocating for dietary precursors limitation, enzyme replacement, and specialized metabolic management to improve long-term patient outcomes.