Carglumic acid: new preparation. An advance in rare urea cycle disorders.

(1) Previously, phenylbutyrate sodium was the only product marketed in France for the treatment of diseases caused by enzyme deficiencies affecting the urea cycle. By a non specific action, this drug partially prevents episodes of hyperammonaemia and their potentially severe consequences. (2) Marketing authorization has now been granted, through the European centralised procedure, for carglumic acid (N-carbamyl L-glutamic acid) as replacement therapy for N-acetylglutamate synthetase deficiency, the rarest urea cycle disorder. This enzyme is crucial for the first step of the urea cycle. (3) Thirteen of the 16 patients in the clinical evaluation dossier, who were treated before the onset of permanent sequelae due to hyperammonaemia, had normal growth and psychomotor development. The optimal dose of carglumic acid is not known. (4) No serious adverse effects have been observed, but too few patients have been treated to identify possible rare adverse effects. There are no data on the effects of carglumic acid in pregnant women. (5) In practice, carglumic acid is now the reference treatment for patients with N-acetylglutamate synthetase deficiency, despite several unknowns.