A case of hyperinsulinism/hyperammonaemia syndrome with reduced carbamoyl-phosphate synthetase-1 activity in liver: a pitfall in enzymatic diagnosis for hyperammonaemia.

We report a patient who was first diagnosed as having congenital carbamoyl-phosphate synthetase-1 (CPS-1) deficiency on the basis of significantly low CPS-1 activity in the liver at 1 year of age. We then started therapy against hyperammonaemia with little effect and, at the age of 15 years, we analysed the GLUD1 gene and found a previously reported gain-of-function mutation in the gene, resulting in a change of her diagnosis to hyperinsulinism/hyperammonaemia (HI/HA) syndrome. This case demonstrates that low CPS-1 activity in liver, however significant it might be, does not always come from a primary CPS-1 deficiency and that we have to take into consideration the possibility of a secondary CPS-1 deficiency, such as HI/HA syndrome.