CPS1 is the rate limiting enzyme of the urea cycle and therefore important for degradation and elimination of ammonia. CPS1 deficiency will result in hyperammonemia and its sequella.
Previous studies have reported a wide range of age and disease severity.
CPS1 deficiency is a rare autosomal recessive disorder with increased frequency in area of high consanguinity as in the Bedouin community in Southern Israel.
We describe 3 families with 10 patients diagnosed biochemically, six of them diagnosed molecularly with CPS1 deficiency, all homozygous to the same novel pathogenic mutation.
All patients were followed in the same metabolic unit. Their novel mutation was studied in an expression model for pathogenicity prediction, and was found to lead to 50% decrease of enzyme activity.
However, not only age presentation and severity is differs between patients as described before, but part of our patients also seem to grow of their disease, with no recurrent episodes of hyperammonemia with advanced age even through triggering events such as intercurrent infections.
One of the possible explanations could be changing gene expressions and modifiers genes, that have to be identified in the future.
