Disorders of Purine and Pyrimidine Metabolism

Abstract

The inherited disorders of purine and pyrimidine metabolism cover a broad spectrum of illnesses with various presentations. These include hyperuricemia, acute renal failure, renal stones, gout, unexplained neurologic deficits (seizures, muscle weakness, choreoathetoid and dystonic movements), developmental disability, intellectual disability, compulsive self-injury and aggression, autistic-like behavior, unex-plained anemia, failure to thrive, susceptibility to recurrent infection (immune deficiency), and deafness. When identified, all family members should be screened. Purines and pyrimidines form the basis of nucleotides and nucleic acids (DNA and RNA) and so are involved in all biologic processes. Metabolically active nucleotides are formed from heterocyclic nitrogen-containing purine bases (guanine and adenine) and pyrimidine bases (cytosine, uridine, and thymine): all cells require a balanced supply of nucleotides for growth and survival. Purines provide the primary source of cellular energy through adenosine triphosphate (ATP) and the basic coenzymes (nicotinamide adenine dinucleotide and its reduced form) for metabolic regulation and play a major role in signal transduction (guanosine triphosphate [GTP], cyclic adenosine mono-phosphate, cyclic guanosine monophosphate). Figure