Affiliations: Pediatric Endocrinology, Diabetology and Metabolism,
University Children's Hospital, Bern, Switzerland | University Institute of Clinical Chemistry,
Inselspital, Bern, Switzerland
Note: [] Corresponding author: Jean-Marc Nuoffer, University Institute of
Clinical Chemistry, Inselspital, Freiburgstrasse, CH-3010 Bern, Switzerland.
Tel.: +41 31 632 95 69; Fax: +41 31 632 48 62; E-mail:
jean-marc.nuoffer@insel.ch
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.
