7 - Inborn errors of urea synthesis

Abstract

This chapter discusses the diseases and management of them caused by inborn errors of urea synthesis. Defects in each of the urea cycle enzymes have been discovered. Because the phenotypes found in carbamyl phosphate synthetase deficiency (CPSD), ornithine transcarbamylase deficiency (OTCD), argininosuccinic acid synthetase deficiency (ASD), and argininosuccinase deficiency (ALD) share many common features, they are discussed as a group distinct from arginase deficiency (AD), which has a quite different phenotype. There is a broad spectrum of clinical presentation in patients with one of CPSD, OTCD, ASD, and ALD. The disease may present during the neonatal period, but much milder variants may first appear later in infancy and childhood, manifested by mild hyperammonemia presenting as episodic lethargy and vomiting. The outlook for survival for infants deficient in CPS, OTC, AS, and AL improved dramatically in 1979, when the concept was introduced that there were pathways and products that would serve for waste nitrogen synthesis and excretion other than ureagenesis and urea.