UNIT 17.1 An Overview of Biochemical Genetics

Biochemical genetics is focused on the pathophysiology, diagnosis, and treatment of inborn errors of metabolism, which result in potentially toxic accumulation of substrate or secondary metabolites, and/or inhibition of reaction products. Early-onset metabolic disorders often present during infancy as acute, life-threatening illnesses; other forms of inborn errors appear later in childhood and are often characterized by progressive neurodegeneration. This unit provides an overview of modern biochemical genetic diagnostic methods used to evaluate a patient's metabolic status via measurement of reaction products or a specific enzyme activity. One such technique, tandem mass spectrometry (MS/MS), has revolutionized population-scale newborn screening for metabolic disorders by providing rapid, accurate, multianalyte quantification on small samples. The combination of expanded newborn screening and novel therapeutic approaches, such as enzyme-replacement therapy, offers significant improvement in the management of metabolic disorders. Keywords: biochemical; genetics; metabolism; enzyme; mass spectrometry; enzyme-replacement therapy