Argininosuccinate synthetase 1

But then can I put to you a sort of a clinical scenario? So say a clinician sees a high citrulline concentration.

How should they think through the differential diagnosis and what distinguishes citrine deficiency from ASS1 deficiency and the other causes of citrullinemia?

Okay, if we take that clinical scenario of an elevated blood citrulline concentration, next steps will depend on the level of citrulline and on few other metabolites.

In principle, there are not many differential diagnoses.

The first condition to think of with elevated blood citrulline is certainly type 1 citrullinemia, so ASS1 deficiency, which is a classical urea cycle defect and often associated with very high citrulline levels, usually much higher than in citrulline deficiency.

Then ASL deficiency, argininosuccinic lyase deficiency, another of the cytosolic and classical UCDs that does have a very specific biomarker, argininosuccinic acid.

Another differential thought would be patients with lysinuric protein intolerance or with a condition called dehydrolipoamide dehydrogenase deficiency, because they can also have elevated citrulline, as it can be the case in pyruvate carboxylase deficiency.

Totally agree.