Chapter 12 - Disorders of purine and pyrimidine metabolism

Abstract

Nucleotide metabolism is directly linked to cellular homeostasis as it is essential for physiological processes such as carbohydrate metabolism, oxidative phosphorylation, essential nucleotide biosynthesis, and signal transduction. The consequences of perturbations in purine and pyrimidine metabolism represent a diverse collection of disorders, differing in both their clinical manifestations and underlying molecular mechanisms. These disorders originate from abnormal enzymatic function in one of four molecular modules: de novo synthesis, catabolism and metabolite recycling, and excretion. Aberrations in these processes result in the depletion of nucleotides or accumulation of toxic intermediates, leading to various pathological outcomes. Because of the potential to intervene therapeutically in some of these disorders, early and accurate diagnosis is vital for diagnosis and treatment, as well as family and reproductive counseling. The mainstay of diagnosis is the analysis of blood and urine purines and pyrimidines. In addition, extracts from erythrocytes may be used to analyze nucleotide profiles for clinical purposes. After confirming a diagnosis, management options are strategically focused on decreasing the overproduction of related metabolites that have an acquired toxicity or replacement of those that are deficient. This chapter provides details of known disorders of purine and pyrimidine metabolism, their clinical presentations, diagnostic methodology, and current treatment options.