Abstract
Urea cycle disorders (UCD) are due to defects of any of its six enzymes or two transporters.
The definitive diagnosis of defects of the three mitochondrial enzymes, N-acetylglutamate
synthase (NAGS), carbamylphosphate synthetase I (CPS1) and ornithine transcarbamylase
(OTC) depends on either molecular mutation analysis or measurement of enzyme activity,
whereas the diagnosis of deficiencies of the three cytosolic enzymes argininosuccinate
synthetase (ASS), argininosuccinate lyase (ASL) and arginase I (ARG1) is usually straightforward,
based on marker metabolites. Enzyme assays for all UCD have been used since their
first description, for disease confirmation and in some instances even for prenatal
diagnosis. The genetic bases of the UCD have only been unraveled from the 1980s; the
last gene cloned being the NAGS gene in 2002. In this review we discuss the enzymatic
assays for all urea cycle enzymes from a historical perspective, their potential and
drawbacks, and the current role of enzymatic analysis in UCD in general.
Keywords
Urea cycle defects - urea cycle enzymes - enzymology - enzyme assays
