1. Common biochemical denominator of urea cycle defects

Based on your previous knowledge, which are the common metabolic findings in patients with different urea cycle defect (except for arginase 1 deficiency)? To help you visualize the common metabolic findings of urea cycle defects (except for arginase 1 deficiency), use arrows (↓, ↑, or →) on the figure below to show the biochemical effects you would expect to find in patients with NAGS, CPS1, OTC, ASS, ASL, and ornithine transporter deficiencies.

Figure 9

Based on the model from: Zschocke and Hoffmann in Vademecum metabolicum

The main biochemical changes would be raised ammonia, raised glutamine, and reduced arginine.

You can see from this that the common biochemical denominator of all urea cycle defects (except arginase 1 deficiency) simply reflects significant impairment of the major functions of this cycle due to inherited enzyme deficiency: 1) impaired detoxification of nitrogen waste (including also nitrogen waste stored in L-glutamine) via urea, and 2) impaired production of conditionally essential L-arginine. Biochemical changes in citrulline, argininosuccinate, and orotic acid, however, are variable and depend on the underlying disease. Therefore, changes in citrulline, argininosuccinate, and orotic acid are important for the differential diagnosis of urea cycle defects. However, this will be discussed later (in module 3).